The emergence of non-canonical amino acids (ncAAs) has enriched the functional pool inherent in canonical amino acids (cAAs). ncAAs are important building blocks in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis because of its environmental friendliness and high efficiency. The breakthrough genetic code expansion (GCE) technique developed in recent years has allowed for the incorporation of ncAAs into target proteins, giving them special functions and biological activities. Biosynthesis of ncAAs and their incorporation into target proteins within a single microbe has become an enticing application of such molecules. Based on that, in this study we first review the biosynthesis methods for ncAAs and analyze the difficulties in biosynthesis. We then summarize the GCE methods and analyze their advantages and disadvantages. Further, we review the application progress of ncAAs and anticipate the challenges and future development directions of ncAAs.

Bacterial resistance to antibiotics is a public health menace that needs urgent efforts to mitigate and forestall their transmission in the general environment. Plasmid-mediated metallo beta-lactamase (MBL) gives bacteria an exceptional ability to transmit resistance genes. This study investigated plasmid-mediated resistance in MBL P. aeruginosa isolates from poultry food chain settings. Cloacal swab samples (n=120) were bacteriologically analyzed for the isolation of P. aeruginosa isolates. Susceptibility studies were performed by the CLSI guideline using selected antibiotics. MBL was phenotypically detected using modified Hodges test, and confirmed using PCR technique. Plasmid curing studies detected the presence of plasmids in the isolates. P. aeruginosa isolates (n=48) showed high levels of reduced susceptibility to cefoxitin (93.8%), imipenem (81.3%), gentamicin (85.4%), amikacin (85.4%), nitrofurantoin (83.3%), ofloxacin (72.9%) and cefotaxime (77.1%). MBL was phenotypically detected in 7 (14%) isolates of P. aeruginosa. The presence of blaIMP-1 and blaIMP-2 MBL genes in P. aeruginosa (n=5) isolates was confirmed by PCR. The PCR did not detect blaVIM-1 and blaVIM-2 MBL genes. The P. aeruginosa isolates were multidrug resistant, with about 50% of the isolates showing multidrug resistance (MDR) to the antibiotics. The genes for MDR in the P. aeruginosa isolates were borne on plasmids, indicating a high possibility of community transmission of MBL resistance genes. Finally, the P. aeruginosa isolates from poultry food chain milieus are multidrug resistant, produce MBL, and harbour their resistance genes on plasmids. Since many antibiotic resistance genes in bacteria are associated with mobile genetic elements (MGEs) like plasmids, it is important to step up actions to mitigate incessant use of antibiotics in poultry and other agricultural practices in Nigeria in order to diminish the evolution and spread of plasmid-mediated resistance which is capable of initiating community acquired infections that may prove difficult to treat in our hospitals with the available antibiotics.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031<0.05), of rodent-proof equipment in the food (2=9.19, P=0.025<0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014<0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

The WRKY gene family in plants regulates the plant's response to drought through regulatory networks and hormone signaling. AfWRKY20 (MT859405) was cloned from A. fruticosa (Amorpha fruticosa,A. fruticosa) seedlings using RT-PCR. The binding properties of the AfWRKY20 protein and the W-box (a DNA cis-acting element) were verified both in vivo and in vitro using EMSA and Dual-Luciferase activity assays. RT-qPCR detected that the total expression level of AfWRKY20 in leaves and roots was 22 times higher in the 30% PEG6000 simulated drought treatment compared to the untreated group. Under the simulated drought stress treatments of sorbitol and ABA (abscisic acid,ABA), the transgenic tobacco with the AfWRKY20 gene showed enhanced drought resistance at the germination stage, with significantly increased germination rate, green leaf rate, fresh weight, and root length compared to the WT (wild type,WT) tobacco. In addition, the SOD (superoxide dismutase,SOD)activity, chlorophyll content, and Fv/Fm ratio of AfWRKY20 transgenic tobacco were significantly higher than those of the WT tobacco under natural drought stress, while the MDA (malondialdehyde,MDA) content and DAB (3,3'-diaminobenzidine,DAB) and NBT (nitroblue tetrazolium,NBT) staining levels were lower. The expression levels of oxidation kinase genes (NbSOD, NbPOD, and NbCAT) in transgenic tobacco under drought stress were significantly higher than those in WT tobacco. This enhancement in gene expression improved the ability of transgenic tobacco to detoxify ROS (reactive oxygen species,ROS). The survival rate of transgenic tobacco after natural drought rehydration was four times higher than that of WT tobacco. In summary, this study revealed the regulatory mechanism of AfWRKY20 in response to drought stress-induced ABA signaling, particularly in relation to the ROS. This finding provides a theoretical basis for understanding the pathways of WRKY20 involved in drought stress, and offers genetic resources for molecular plant breeding aimed at enhancing drought resistance.

Hospital readmission and length of stay prediction provide info to manage hospitals’ bed capacity and the number of required staff, especially during pandemics. We present a hybrid deep model called Genetic Algorithm-Optimized Convolutional Neural Network (GAOCNN) with a unique preprocessing method to predict hospital readmission and the length of stay in patients having various conditions. GAOCNN uses one-dimensional convolutional layers to predict hospital readmission and length of stay. The parameters of the layers are optimized using a genetic algorithm. To show the performance of the proposed model in patients with various conditions, we evaluate the model under three healthcare datasets; the Diabetes 130-US hospitals dataset, the COVID-19 dataset, and the MIMIC-III dataset. The diabetes 130-US hospitals dataset has information on both readmission and the length of stay, while COVID-19 and MIMIC-III datasets just include information on the length of stay. Experimental results show that the proposed model’s accuracy for hospital readmission is 97.2% for diabetic patients. Also, the accuracy of the length of stay prediction is 89%, 99.4%, and 94.1% for diabetic, COVID-19, and ICU patients, respectively. These results confirm the superiority of the proposed model compared to existing methods. Our findings offer a platform for managing healthcare funds and resources for patients with various diseases.

The aim of this paper is to optimize thickness variation function of simply supported and cantilever beams, in terms of maximizing gaps between chosen neighboring frequencies and analyze obtained results. The optimization results are examined in terms of achieving the objective function (related to eigenproblem), but also in terms of their dynamics stiffness (forced vibrations excited by point harmonic load). In the optimization process, a Genetic Algorithm was used. Problems related to structural dynamics were solved by FEM implementation into the algorithm. Sample results were presented, and the developed algorithm was analyzed in terms of result convergence by examining several variable parameters. The authors demonstrated the validity of applying the described optimization tool to the presented problems. Conclusions were drawn regarding the correlation between stiffness and mass distribution in the optimized beams and the natural frequency modes in terms of which they were optimized.

Distributed electric propulsion technology has great potential and advantage in the development of drones. In this paper, to study the slipstream effect of distributed propeller, the actuator disk method was used to verify a single propeller, and the calculated thrust was in good agreement with the test results. Then, based on the actuator disk method, the influence of different installation positions on the slipstream effect was studied, and the distributed propeller layout was optimized by genetic algorithm. The analysis results showed that lift of the wing will be larger when the propellers are higher than the wing. When the relative height between the propeller and the wing is zero, the drag is the lowest. The influence of disk diameter on the slipstream is that the larger the diameter is, the higher the lift force and the drag force are. The slipstream effect of the optimized propeller distribution improves the lift-drag ratio of the wing, by 108.5% in the initial lift-drag ratio.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

The KCNA1 gene encodes Kv1.1 voltage-gated potassium channel α subunits, which are crucial for maintaining healthy neuronal firing and preventing hyperexcitability. Mutations in the KCNA1 gene can cause several neurological diseases and symptoms, such as episodic ataxia and epilepsy, which may occur alone or in combination, making it challenging to establish simple genotype-phenotype correlations. Previous analyses of human KCNA1 variants have shown that epilepsy-linked mutations tend to cluster in regions critical for the channel’s pore, whereas EA1-associated mutations are evenly distributed across the length of the protein. In this review, we examine 17 recently discovered pathogenic or likely pathogenic KCNA1 variants to gain new insights into the molecular genetic basis of KCNA1 channelopathy. We provide the first systematic breakdown of disease rates for KCNA1 variants in different protein domains, uncovering potential location biases that influence genotype-phenotype correlations. Our examination of the new mutations strengthens the proposed link between the pore region and epilepsy and reveals new connections between epilepsy-related variants, genetic modifiers, and respiratory dysfunction. Additionally, the new variants include the first two gain-of-function mutations ever discovered for KCNA1, the first frameshift mutation, and the first mutations located in the cytoplasmic N-terminal domain, broadening the functional and molecular scope of KCNA1 channelopathy. Moreover, the recently identified variants highlight emerging links between KCNA1 and musculoskeletal abnormalities and nystagmus, conditions not typically associated with KCNA1. These findings improve our understanding of KCNA1 channelopathy and promise to enhance personalized diagnosis and treatment for individuals with KCNA1-linked disorders.

In recent years, the ecological and economic values of forest plants have been gradually recognized worldwide. However, the growing global demand for new forest plant varieties with higher wood production capacity and better stress tolerance cannot be satisfied by conventional phenotype-based breeding, marker-assisted selection, and genomic selection. In the recent past, diverse omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and metabolomics, have been developed rapidly, providing powerful tools for the precision genetic breeding of forest plants. Genomics lays a solid foundation for understanding complex biological regulatory networks, while other omics technologies provide different perspectives at different levels. Multi-omics integration has combined the different omics technologies, becoming a powerful tool for genome-wide functional element identification in forest plant breeding. This review summarizes the recent progress of omics technologies and their applications in the genetic studies of forest plants. It will provide forest plant breeders with an elementary knowledge of multi-omics techniques for future breeding programs.

Optimization using Genetic Algorithms (GA) is a well-known strategy in several scientific disciplines. The crossover is an essential operator of the Genetic Algorithm. It has been an active area of research to develop sustainable forms for this operand. In this work, a new crossover operand is proposed. This operand depends on giving an elicited description for the chromosome with a new structure for alleles of the parents. It is suggested that each allele has two attitudes, one attitude differs contrastingly with the other, and both of them complement the allele. Thus, in case of one attitude is good, the other should be bad. This is suitable for many systems which contain admired parameters and unadmired parameters. The proposed crossover would improve the desired attitudes and damp the undesired attitudes. The proposed crossover can be achieved in two stages: the first stage is a mating method for both attitudes in one parent to improving one attitude at the expense of the other. The second stage comes after the first improvement stage for mating between different parents. Hence, two concurrent steps for improvement would be applied. Simulation experiments for the system shows improvement in the fitness function. The proposed crossover could be helpful in different fields, especially to optimize routing algorithms and network protocols, an application that has been tested as a case study in this work.

The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. But research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and four RNA mononucleotides in three charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the -1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least one of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomized assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology.

Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focus on pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by pfhrp2. Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69 % in the study area. About 85% of the major epitopes targeted by Monoclonal antibodies (MAbs) in RDT were identified. Our study suggests that the extensive sequence variation in the pfhrp2 could contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay demonstrated that variant c.449+5G>A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

Background: Studies have linked bats to outbreaks in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Method: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total 1732 and 1866 individual bat faecal samples were collected respectively. Coronaviruses and bat species were amplified using PCR systems respectively. Results: Analysis of the coronavirus sequences revealed a high genetic diversity and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site, 16.5% and 38.9% at Magweto site for small insectivorous bats and Macronycteris gigas respectively. Conclusion: The higher risk of bat coronaviruses exposure for humans ranged from December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.

Arthropods are the most abundant and diverse animals on earth. Among them, pancrustaceans are an ancient and morphologically diverse group, comprising a wide range of aquatic and semi-aquatic crustaceans as well as the insects, which emerged from crustacean ancestors to colonise most terrestrial habitats. Within insects, Drosophila stands out as one of the most powerful animal models, making major contributions to our understanding of development, physiology and behaviour. Given these attributes, crustaceans provide a fertile ground for exploring biological diversity through comparative studies. However, beyond insects, few crustaceans are developed sufficiently as experimental models to enable such studies. The marine amphipod Parhyale hawaiensis is currently the best established crustacean system, offering year-round accessibility to developmental stages, transgenic tools, genomic resources, and established genetics and imaging approaches. The Parhyale research community is small but diverse, investigating the evolution of development, regeneration, aspects of sensory biology, chronobiology, bioprocessing and ecotoxicology.

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We show that an integrated approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n=290,584). Likewise, integrating PRS with self-reports on birth weight (n=172,239) and comparative body size at age ten (n=287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements.

This study aims to analyze the pedigrees of calves affected by one of three congenital defects: aplasia genitalis, atresia ani et recti and hernia cerebralis. The defects were diagnosed by veterinary surgeons in the Czech surveillance program for bovine genetic disorders. The sires fathering affected calves were born in the Czech Republic or imported from 1986-2001. The cases occurred on farms across the Czech Republic. The pedigree of each case was examined for common maternal and paternal ancestors (inbreeding loops) and for ancestors shared by other cases of the defect. The 13 calves affected by aplasia genitalis had common ancestors in all cases. The results indicate hereditary causation with recessive inheritance. Additionally, in atresia ani et recti, some of the pedigrees of 25 affected calves support hereditary causation, and repeating ancestors were found for 11 calves. In contrast, our analysis of 11 hernia cerebralis cases did not confirm the genetic background. We demonstrated that the pedigree analysis of congenital defects could help in controlling genetic health, although the final goal in terms of inherited defects is the description of causal genes and mutations. Measures to control sires that father affected calves should be appropriate under the current knowledge, which include culling or prudent use of breeding with the monitoring of descendants.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

Temperature is one of the most important range-limiting factors for many seaweeds. Driven by the recent climatic changes, rapid northward shifts of species’ distribution ranges can potentially modify the phylogeographic signature of Last Glacial Maximum such as increased genetic diversity at lower latitudes. To explore this question in detail in the kelp Saccharina latissima, we used microsatellites and double digest RAD-sequencing derived SNPs on S. latissima sporophytes sampled within 11 sites spanning the entire European Atlantic latitudinal range of this species. In addition, we checked for statistical correlation between genetic marker allele frequencies and three environmental proxies (sea surface temperature, salinity, and water turbidity). Our findings revealed that genetic diversity was significantly higher for the northern localities compared to the southern ones in contrast to the expected phylogeographic pattern. This suggests that the southernmost S. latissima populations are negatively affected by the recent climatic changes but also that the recolonization of S. latissima range following the LGM may have occurred from northerly refugia. Seven SNPs and 12 microsatellite alleles were found to be significantly associated with at least one of the three environmental variables. We discuss the potential adaptive functions of the genes associated with the outlier markers and the importance of these markers for successful conservation and aquaculture strategies for S. latissima in this age of rapid global change.

Upon inbreeding, the architecture of the inbreeding load shifts as selection purges strongly deleterious recessive mutations and drift fixes many milder ones. Most small inbred populations show limited genetic variation while crosses between such populations commonly express pronounced heterosis, confirming fixation. In contrast, purging appears to be limited in that inbred populations often retain substantial inbreeding depression. In addition we have the enigma Darwin noted: purely selfing taxa are unknown. Because both purging and fixation reduce inbreeding depression and load, another mechanism must exist to sustain these. Background selection and the associations that develop among alleles in small inbred populations will shift the architecture of the load potentially creating blocks of recessive mutations linked in repulsion. This would generate pseudo-overdominance that could sustain these “PODs” and inbreeding load. Recombination and crosses between lineages could erode PODs. Crosses between populations fixed for different mutations would generate high pseudo-overdominance, enhancing heterosis and potentially POD formation. New recessive mutations arising within PODs would reinforce overdominance. PODs should generate clear genetic signatures including genomic hotspots of heterozygosity and linkage disequilibrium containing alleles at intermediate frequency generating segregating load. Results from several simulation and empirical studies match these predictions. Further simulations and comparative genomic analyses are needed to rigorously test whether PODs exist in sufficient strength and number to generate persistent inbreeding depression and load in inbred lineages.

Genomic selection (GS) is a predictive approach that was build up to increase the rate of genetic gain per unit of time in breeding programs. It has emerged as a valuable method for improving complex traits that are controlled by many genes with small effect. GS enables the prediction of breeding value of candidate genotypes for selection. In this work we address important issues related to GS and its implementation in tomato breeding context. Genomic constrains and critical parameters affecting the accuracy of prediction in such crop such as phenotyping, genotyping training population composition and size and statistical method should be carefully evaluated. Comparison of GS approaches for facilitating the selection of tomato superior genotypes during breeding program are also discussed. GS applied to tomato breeding has already shown to be feasible. We illustrated how GS can improve the rate of gain in elite lines selection, descendent and in backcross schemes. The GS schemes begin to be delineated and computer science can provide support for future selection strategies. A new breeding framework is beginning to emerge for optimizing tomato improvement procedures.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to a severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors which involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.

Yeasts belonging to the Metschnikowia genus are particularly interesting for the unusual formation of only two needle-shaped ascospores during their mating cycle. Presently, the meiotic process that can lead to only two spores from a diploid zygote is poorly understood. The expression of fluorescent nuclear proteins should allow the meiotic process to be visualized in vivo; however, no large-spored species of Metschnikowia has ever been transformed. Accordingly, we aimed to develop a transformation method for Metschnikowia borealis, a particularly large-spored species of Metschnikowia, with the goal of enabling the genetic manipulations required to study biological processes in detail. Genetic analyses confirmed that M. borealis, and many other Metchnikowiacea, are CUG-Ser yeasts. Codon-optimized selectable markers lacking CUG codons were used to successfully transform M. borealis by electroporation and lithium acetate, and transformants appeared to be the result of random integration. Mating experiments confirmed that transformed-strains were capable of generating large asci and undergoing recombination. Finally, random integration was used to transform an additional 18 yeast strains, and all attempts successfully generated transformants. The results provide a simple method to transform many yeasts from an array of different clades and can be used to study or develop many species for various applications.

The current clinical model for genetic-testing is based on clinical-criteria/family-history(FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intense and misses >50% of individuals/mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and the acceptability/awareness is rising. MEDLINE/EMBASE/Pubmed/CINAHL/PsychINFO databases were searched using a free-text and MeSH terms; reference lists of publications retrieved screened; additionally web-based platforms, Google, and clinical-trial registries were searched. Quality of studies were evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish-population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines to population-based BRCA-testing in the Jewish-population. Population panel-testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast/ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general-population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

Widely used in hydraulics, the Colebrook equation for flow friction relates implicitly to the input parameters; the Reynolds number, Re and the relative roughness of inner pipe surface, ε/D with the output unknown parameter; the flow friction factor, λ; λ=f(λ, Re, ε/D). In this paper, a few explicit approximations to the Colebrook equation; λ≈f(Re, ε/D), are generated using the ability of artificial intelligence to make inner patterns to connect input and output parameters in explicit way not knowing their nature or the physical law that connects them, but only knowing raw numbers, {Re, ε/D}→{λ}. The fact that the used genetic programming tool does not know the structure of the Colebrook equation which is based on computationally expensive logarithmic law, is used to obtain better structure of the approximations which is less demanding for calculation but also enough accurate. All generated approximations are with low computational cost because they contain a limited number of logarithmic forms used although for normalization of input parameters or for acceleration, but they are also sufficiently accurate. The relative error regarding the friction factor λ, in best case is up to 0.13% with only two logarithmic forms used. As the second logarithm can be accurately approximated by the Padé approximation, practically the same error is obtained also using only one logarithm.

Fungal endophytes are the most ubiquitous plant symbionts on earth and are phylogenetically diverse. Studies on the fungal endophytes in tobacco have shown that they are widely distributed in the leaves, stems, and roots, and play important roles in the composition of the microbial ecosystem of tobacco. Herein, we analyzed and quantified the endophytic fungi of healthy tobacco leaves at the seedling (SS), resettling growth (RGS), fast-growing (FGS), and maturing (MS) stages at three altitudes [600 (L), 1000 (M), and 1300 m (H)]. We sequenced the ITS region of fungal samples to delimit operational taxonomic units (OTUs) and phylogenetically characterize the communities. The result showed the number of clustering OTUs at SS, RGS, FGS and MS were greater than 170, 245, 140, and 164, respectively. At the phylum level, species in Ascomycota and Basidiomycota had absolute predominance, representing 97.8% and 2.0 % of the total number of species. We also found the number of unique fungi at the RGS and FGS stages were higher than those in the other two stages. Additionally, OTU richness was determined by calculating the Observed Species, Shannon, Simpson, Chao1, ACE, Goods coverage and PD_whole_tree indices based on the total number of species. Our results showed RGS samples had the highest diversity indices. Furthermore, we found that the diversity of fungal communities tended to decrease with increasing tobacco growth altitude. The results from this study indicated that the tobacco harbors an abundant and diverse endophytic fungal population, which provides new opportunities for exploration their potential utilization.

This paper proposes a method based on genetic algorithm (GA) for the security-constrained optimal dispatch of integrated natural gas and electricity networks, considering operating scenarios in both energy systems. The mathematical formulation of the optimization problem consists of a multi-objective function which aims to minimize both cost of thermal generation (diesel and natural gas) as well as the production and transportation of natural gas. The joint gas-electricity system is modeled by two separate groups of nonlinear equation, which are solved by the combination of Newton's method with the GA. The applicability of the proposed method is tested in the Belgian gas network integrated with the IEEE 14-bus test system and a 15-node natural gas network integrated with the IEEE 118-bus test system. The results demonstrate that the proposed method provides efficient and secure solutions for different operating scenarios in both energy systems.

Nearly 50 years ago, Francis Crick propounded the frozen accident scenario for the evolution of the genetic code along with the hypothesis that the early translation system consisted primarily of RNA. Under the frozen accident perspective, the code is universal among modern life forms because any change in codon assignment would be highly deleterious. The frozen accident can be considered the default theory of code evolution because it does not imply any specific interactions between amino acids and the cognate codons or anticodons, or any particular properties of the code. The subsequent 49 years of code studies have elucidated notable features of the standard code, such as high robustness to errors, but failed to develop a compelling explanation for codon assignments. In particular, stereochemical affinity between amino acids and the cognate codons or anticodons does not seem to account for the origin and evolution of the code. Here I expand Crick’s hypothesis on RNA-only translation system by presenting evidence that this early translation already attained high fidelity that allowed protein evolution. I outline an experimentally testable scenario for the evolution of the code that combines a distinct version of the stereochemical hypothesis, in which amino acids are recognized via unique sites in the tertiary structure of proto-tRNAs, rather than by anticodons, expansion of the code via proto-tRNA duplication and the frozen accident.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

In genetic conflicts, driver and killer elements achieve biased survival, replication, or transmission over sensitive and targeted elements through a wide range of molecular mechanisms, including mimicry. Driving mechanisms manifest at all organismal levels, from the biased propagation of individual genes, as demonstrated by transposable elements, to the biased transmission of genomes, as illustrated by viruses, to the biased transmission of cell lineages, as in cancer. Targeted genomes are vulnerable to molecular mimicry through the conserved motifs they use for their own signaling and regulation. Mimicking these motifs enables a selfish element to control core target processes, and can occur at the sequence, structure, or functional level. Molecular mimicry was first appreciated as an important phenomenon more than twenty years ago. Modern genomics technologies, databases, and machine learning approaches offer tremendous potential to study the distribution of molecular mimicry across genetic conflicts in nature. Here, we explore the theoretical expectations for molecular mimicry between conflicting genomes, the trends in molecular mimicry mechanisms across known genetic conflicts, and outline how new examples can be gleaned from population genomic datasets. We discuss how mimics involving short sequence-based motifs or gene duplications can evolve convergently from new mutations. Whereas, processes that involve divergent domains or fully-folded structures occur among genomes by horizontal gene transfer. These trends are largely based on a small number of organisms and should be reevaluated in a general, phylogenetically independent framework. Currently, publicly available databases can be mined for genotypes driving non-mendelian inheritance patterns, epistatic interactions, and convergent protein structures. A subset of these conflicting elements may be molecular mimics. We propose approaches for detecting genetic conflict and molecular mimicry from these datasets.

The study titled "Molecular Choreography of DNA: Insights and Innovations" explores the intricate dance of DNA, shedding light on its structure, function, and regulation. This comprehensive review delves into the historical significance of DNA research, from Watson and Crick's double helix discovery to recent innovations in genomics and molecular biology. The review highlights DNA's roles in replication, repair, gene regulation, and chromatin dynamics, emphasizing the precision and complexity of its molecular choreography. Innovations like CRISPR-Cas9 gene editing and advanced sequencing technologies have revolutionized our understanding of DNA, opening new avenues for scientific exploration. This study aims to provide readers with a deeper appreciation of DNA's central role in life's choreographed processes.

Climate change, growing world population and increasing food demand require higher yields and adaptability of crops, including spring bread wheat. Modern plant breeding based on achievements of genetics has a significant impact on plant resistance to diseases, climate variability and other factors. Genome wide association studies (GWAS) is one of genetics tools for mining of genome loci associated with economically important traits. In the current study, we applied GWAS to reveal QTL for spike productivity and grain quality using a panel of spring varieties of Triticum aestivum L. bred in different decades of the last century in Russia and Germany. The study has enabled to find new genetic markers associated with grain yield and quality. Studying genetic basis of grain yield and quality by comparison of wheat varieties from different breeding periods, including landraces preserved as the source of valuable genetic diversity for breeding and genetic studies, makes it possible not only to understand selection processes in the past, but also to develop strategies for future breeding work.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

Breadfruit [Artocarpus altilis (Parkinson) Fosberg] is recognized as a tropical fruit tree crop with great potential to contribute to food and nutrition security in the Caribbean and other tropical regions. However, the genetic diversity and identification of germplasm in the Caribbean and elsewhere is not well understood and documented. This hampers the effective conservation and use of the genetic resources of the tree crop for commercial activities. This study assessed the genetic identity, diversity, ancestry, and phylogeny of breadfruit germplasm existing in Caribbean and recently introduced accessions using 117 SNPs from 10 SSR amplicon sequences. The results showed that there was high genetic diversity in the breadfruit germplasm in the Caribbean, as well as the newly introduced breadfruit accessions based on nucleotide diversity (π_T) and nucleotide polymorphism (θ_W). Furthermore, based on these measures of genetic diversity, there were no significant differences between existing Caribbean breadfruit accessions and newly introduced breadfruit accessions which are known to be highly diverse. Ancestry and phylogeny analysis corroborated the genetic relatedness of these two groups with accessions of these groups being present in both main germplasm clusters. This suggests that the existing Caribbean breadfruit germplasm harbors a higher level of genetic diversity than expected.

The utilization of wild genera in sugarcane has been recognized as an important strategy to enhance the genetic base to impart biotic and abiotic stress tolerance in hybrid cultivars. A set of 15 Erianthus procerus derived hybrids along with five popular check varieties were evaluated for two years (2018–19 and 2019–20) for agro-morphological, quality, physiological traits and three years (2018–19, 2019–2020, and 2020–21 for winter sprouting potential. The E. procerus hybrid GU 12-19 recorded the highest winter sprouting potential with a winter sprouting index (WSI) of 10.6 and a percent superiority of 279 over best check (Co 0238) followed by GU 12-22 with WSI: 8.5 and % superiority over best check was 204. The other top-performing hybrids, GU 12-21 and GU 12-29, recorded the excellent winter sprouting potential with WSI of 7.2 and 6.9 respectively. The four E. procerus hybrids identified with higher WSI were also resistant to the prevalent races of red rot in both tropical and subtropical conditions. The association analysis revealed significant correlations between various traits, particularly fibre content with a maximum number of associations, which indicates its multifaceted impact on sugarcane characteristics. Principal component analysis (PCA) summarized the data, explaining 57.6% of the total variation for measured traits and genotypes, providing valuable insights into the performance and characteristics of the E. procerus-derived hybrids under subtropical climate. The anthocyanin content of E. procerus hybrids was better than the check varieties with a mean of 0.147 (2018–19) and 0.144 (2019–20) and range of 0.123–0.179 (2018–19) and 0.111–0.172 (2019–20), anthocyanin plays a vital role in mitigating the cold injury, acting as an antioxidant in cool weather conditions, particularly in sugarcane. Further, seven hybrids recorded more than 22% fibre threshold, indicating their industrial potential. These hybrids would be potential donors for cold tolerance and high ratooning ability along with red rot resistance under subtropical climate.

The article presents a hybrid method for calculating the chemical composition of steel with the required hardness after cooling from the austenitizing temperature. Artificial neural networks and genetic algorithms were used to develop the model. Based on 550 diagrams of continuous cooling transformation (CCT) of structural steels available in the literature, a dataset of experimental data was created. Artificial neural networks were used to develop a hardness model describing the relationship between the chemical composition of the steel, the austenitizing temperature, and the hardness of the steel after cooling. A genetic algorithm was used to identify the chemical composition of the steel with the required hardness. The value of the objective function was calculated using the neural network model. The developed method for identifying the chemical composition was implemented in a computer application. Examples of calculations of mass concentrations of steel elements with the required hardness after cooling from the austenitizing temperature are presented. The model proposed in this study can be a valuable tool to support chemical composition design by reducing the number of experiments and minimizing research costs.

Curdlan is a water-insoluble polymer that has structure and gelling properties useful in a wide variety of applications such as in medicine, cosmetics, packaging and the food and building industries. The capacity to produce curdlan has been detected in certain soil-dwelling bacteria of various phyla, although the role of curdlan in their survival remains unclear. One of the major limitations of the extensive use of curdlan in industry is the high cost of production during fermentation, partly because production involves specific nutritional requirements such as nitrogen limitation. Engineering of the industrially relevant curdlan-producing strain Agrobacterium sp. ATTC31749 is a promising approach that could decrease the cost of production. Here, during investigations on curdlan production, I found that curdlan was deposited as a capsule. Curiously, only a part of the bacterial population produced a curdlan capsule. This heterogeneous distribution appeared to be due to the activity of Pcrd, the native promoter responsible for the expression of the crdASC biosynthetic gene cluster. To improve curdlan production, Pcrd was replaced by a promoter (PphaP) from another Alphaproteobacterium, Rhodobacter sphaeroides. Compared to Pcrd, PphaP was stronger and only mildly affected by nitrogen levels. Consequently, PphaP dramatically boosted crdASC gene expression and curdlan production. Importantly, the genetic modification overrode the strict nitrogen depletion regulation that presents a hindrance for maximal curdlan production and from nitrogen rich, complex media, demonstrating excellent commercial potential for achieving high yields using cheap substrates under relaxed fermentation conditions.

Fusarium spp. are commonly associated with the root rot complex of soybean (Glycine max). Previous surveys identified six common Fusarium species from Manitoba, including F. oxysporum, F. redolens, F. graminearum, F. solani, F. avenaceum and F. acuminatum. This study aimed to determine their pathogenicity, assess host resistance and evaluate the genetic diversity of Fusarium spp. isolated from Canada. Pathogenicity was tested on two cultivars, ‘Akras’ (moderate resistance) and ‘B150Y1’ (susceptible), under greenhouse conditions. The virulence of the fungal isolates varied, with root rot severities ranging from 1.5 to 3.3 on a 0-4 scale. The six species were used to screen a panel of 20 Canadian soybean cultivars for resistance in a greenhouse. Cluster and principal component analyses were conducted based on the same traits as for the pathogenicity study. Two of the cultivars, ‘P15T46R2’ and ‘B150Y1’, were consistently found to be tolerant to F. oxysporum, F. redolens, F. graminearum and F. solani. To investigate the incidence and prevalence of Fusarium spp. in Canada, fungi were isolated from 106 soybean fields surveyed across Manitoba, Saskatchewan, Ontario and Quebec. Two-hundred twenty-one Fusarium isolates were identified, with phylogenetic analyses indicating diversity of the isolates in the major soybean production regions of Canada.

Zooplankton and ichthyoplankton community assessments depend on species diagnostics, yet morphological identifications are time consuming, require taxonomic expertise, and are hampered by lack of diagnostic characters –particularly for larval stages. Metabarcoding can identify multiple species in communities from short DNA sequences in comparison to reference databases. To evaluate species resolution across phylogenetic groups and food webs of zooplankton and ichthyoplankton, we compare five metabarcode mitochondrial (mt)DNA markers from gene regions of (a)cytochrome c oxidase subunit I, (b) cytochrome b, (c) 16S ribosomal RNA, and (d) 12S ribosomal RNA for DNA extracted from net tows in the Northeastern Pacific Ocean’s Salish Sea across seven sites and two seasons. Species resolved by metabarcoding are compared to invertebrate morphological identifications and biomass estimates. Results indicate that species resolution for different zooplankton and ichthyoplankton taxa can markedly vary among gene regions and markers, and in comparison to morphological identifications. Thus, researchers seeking “universal” metabarcoding should take caution that several markers and gene regions likely will be needed; all will miss some taxa and yield incomplete overlap. Species resolution requires careful attention to taxon marker selection and coverage in reference sequence repositories. In summary, combined multi-marker metabarcode and morphological approaches improve broadscale zooplankton diagnostics.

Machine Learning (ML) has brought about a transformative era in reactor operations, reshaping monitoring, control, and optimization strategies. This survey comprehensively explores the diverse spectrum of ML applications in industrial reactors. From real-time sensor analysis ensuring reactor functionality to adaptive control algorithms ensuring stability, ML's impact is profound and multifaceted. The benefits of ML are equally evident in optimization, encompassing performance trend prediction, proactive maintenance, and fine-tuning of operations for enhanced efficiency. This review identifies dominant ML techniques, operations stages receptive to ML integration, core data sources, and critical input-output parameters. Aimed at both academics and practitioners, this exploration enriches reactor technologies, unlocking their full potential through insights driven by ML.

Sarocladium and Fusarium species are commonly identified as causal agents of rice sheath rot disease worldwide. However, limited knowledge exists about their genetic, pathogenic, and toxigenic diversity in sub-Saharan African (SSA) countries, where an increasing incidence of this disease has been observed. This study aimed at identifying, characterizing, as well as assessing the genetic, pathogenic, and toxigenic diversity of the pathogens associated with rice sheath rot disease in Mali, Nigeria, and Rwanda. In this study seventy fungal isolates were obtained from rice plants displaying disease symptoms on research and farmer’s fields in Mali, Nigeria, and Rwanda. Thus, an extensive comparative analysis was conducted to assess their genetic, pathogenic, and toxigenic diversity. The Fusarium spp. were characterized using the translation elongation factor (EF-1α) region, while a concatenation of Internal Transcribed Spacer (ITS) and Actin-encoding regions were used to resolve Sarocladium species. Phylogenetic analysis revealed four Fusarium species complexes. The dominant complex in Nigeria was the Fusarium incarnatum-equiseti species complex (FIESC), comprising F. hainanense, F. sulawesiense, F. pernambucatum, and F. tanahbumbuense, while F. incarnatum was found in Rwanda. The Fusarium fujikuroi species complex (FFSC) was predominant in Rwanda and Mali, with species such as F. andiyazi, F. madaense, and F. casha in Rwanda, and F. annulatum and F. nygamai in Mali. F. marum was found in Nigeria. Furthermore, Fusarium oxysporum species complex (FOSC) members, F. callistephi and F. triseptatum, were found in Rwanda and Mali, respectively. Two isolates of F. acasiae-mearnsii, belonging to the Fusarium sambucinum species complex (FSAMSC) were obtained in Rwanda. Isolates of Sarocladium which were previously classified in three phylogenetic groups were resolved into three species which are: attenuatum, oryzae and sparsum. S. attenuatum was dominant in Rwanda, while S. oryzae and S. sparsum were found in Nigeria. Also, the susceptibility of FARO44, a rice cultivar released by Africa Rice Centre (AfricaRice) was tested against isolates from the four Fusarium species complexes and the three Sarocladium species. All isolates evaluated could induce typical sheath rot symptoms albeit with varying disease development levels. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine variation in the in vitro mycotoxins of the Fusarium species. Regional differences were observed in the in vitro mycotoxins profiling. Out of the forty-six isolates tested, nineteen were able to produce one to four mycotoxins. Notably, very high zearalenone (ZEN) production was specific to the two F. hainanense isolates from Ibadan-Nigeria, while Fusarium nygamai isolates from Mali produced high amounts of fumonisins. To the best of our knowledge, it seems this study is the first to elucidate genetic, pathogenic, and toxigenic diversity of Fusarium species associated with the rice sheath rot disease complex in selected countries in SSA.

When using meta-heuristic optimization approaches for optimization, a large number of samples are required. In particular, when generating subgeneration, the utilization of existing samples is low and the number of individuals is high. Therefore, surrogate-based optimization has been developed, which greatly reduces the number of individuals in the subgeneration and the cost of optimization. In complex air supply scenarios, single-objective optimization results may not be comprehensive; therefore, this paper developed a double-objective air supply optimization method based on the Kriging surrogate model and Non-dominated Sorting Genetic Algorithms-II. And proposed the infill criteria based on clustering to advance the Pareto Frontier. The method was validated by an inverse prediction case, and in particular, the problems when based on 3D steady-state simulations were analyzed. The results showed that the method can quickly achieve an approximate prediction of the boundary conditions (when prediction were made based on experimental data, the number of simulations was 82 and the average error was 6.8%). Finally, the method was used to optimize the air supply parameters of a dual-aisle, single-row cabin. The Pareto set suggested that an airflow organization with dual circulation may be optimal.

The genus Vigna is penta-tropical having more than 200 species with many desirable economically important traits. The aim of study was to validate the in-silico polymorphism of whole genome sequence developed mungbean specific SSR markers and their transferability among the different Vigna species. The present study utilized a set of 200 SSR markers developed from whole genome sequence of mungbean and validated using a diversity panel of 25 accessions which belongs to 13 Vigna species. Out of 200 SSR markers, 130 markers (65%) were polymorphic across the various Vigna species and the number of alleles amplified varied between 7 to24. The SSR markers showed more than 90 percent transferability across the different Vigna species accessions. Based on allelic data, the 25 Vigna accessions grouped into three clusters based upon the unweighted pair group method with arithmetic mean (UPGMA) phylogenetic tree. The principal co-ordinates analysis (PCA) biplot graph and UPGMA based neighbor joining clustering diagram showed similar pattern of Vigna accessions distribution. The population structure assessment has grouped the cultivated and wild species accessions into two sub-population. The estimated marker parameters such as polymorphic information content (0.09 – 0.84), marker index (0.091 – 3.342) and effective multiplex ratio (1.0 – 4.0) suggested their adequacy in several genetic studies such as parental selection, hybrid testing, genetic mapping and marker aided breeding programmes for genetic enhancement of species belonging to the Vigna genus.

Life is supported by metabolism, a vital physiological activity. It guarantees enough energy available to power every cellular activity. The primary cellular substrate, glucose, is where the majority of the energy needed by the cell to support all other life activities and the growth of living creatures is derived. The quality of life is greatly impacted by any disease or flaw that alters the metabolism of glucose. There is no known cure for the metabolic illness known as diabetes. As diabetes is so varied, the only effective treatments would be based on precision medicine and a molecular strategy. This review covers a wide range of topics, including the ability to recognize the various forms of diabetes, the anthropogenic and genetic influence of the cause of diabetes, the severity of the various forms of diabetes, its potential existential risk, the disease burden, and clinical methods for diagnosing them. The most recent research goes on to recommend ways to ameliorate the disease, including diet-based management, biotherapies, and other individual lifestyle choices. Futuristic therapy using molecular biology approach was suggested. Recent research found a direct correlation between an individual's lifestyle and the rate of gene mutation in diabetes. There is an existential risk associated with the sickness as the rate of the spread of the disease among population globally is faster than the world's population growth rate. It is possible to think of diabetes as a silent pandemic.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that TS 1100T>C polymorphisms increased disease susceptibility in several groups, while the TS 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

Background: Disorders of immunity are poorly recognised in some rare multisystem genetic con-ditions. We aim to describe syndromic features and immunological defects in children with syn-dromic primary immunodeficiencies (sPIDs). Methods: This is a retrospective descriptive study of children aged 0-18 years with sPIDs under the care of the paediatric immunology service at the Bristol Royal Hospital for Children, United Kingdom from January 2006 to September 2021. Results: sPIDs were identified in 36 patients. Genetic diagnoses which are not commonly associ-ated with PIDs and not included in the International Union of Immunological Societies classifica-tion were present in 7/36 (19%): Trisomy 22, Arboleda-Tham syndrome, 2p16.3 deletion syn-drome, supernumerary ring chromosome 20 syndrome, Myhre syndrome, Noonan syndrome, trichothiodystrophy/Cockayne syndrome complex. Recurrent and/or severe infections were the commonest clinical features (n=33, 92%). Approximately half had combined immunodeficiency or antibody deficiency. Commonest extra-immunological manifestations include dysmorphism (72%), disorders of nervous (78%), musculoskeletal (69%), haematology/lymphatic (58%), and gastrointestinal, hepatic/pancreatic (58%) systems. Conclusions: Patients with sPIDs often have multiorgan involvement and some are non-immunologically mediated. There should be low threshold to clinically assess and investi-gate for disorders of immunity in any patients with syndromic features especially when they pre-sent with recurrent/severe/opportunistic infections, features of immune dysregulation, autoin-flammation or lymphoproliferation.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.

We have performed the first comparative analysis of the potential of two physiologically-diverse model cyanobacteria, Synechococcus PCC 7002 (S.7002) and Synechococcus PCC 7942 (S.7942), for the photosynthetic production of four chemically-different high-value terpenes: two monoterpenes limonene and pinene, and two sesquiterpenes bisabolene and farnesene. We showed, for the first time, that S.7002 and S.7942 can produce farnesene and bisabolene, respectively. Both cyanobac-teria produced farnesene (S.7942 better than S.7002) more efficiently than the other tested terpenes (especially pinene the weakest produced terpene). S.7002 produced limonene better than bisabo-lene, whereas S.7942 produced bisabolene better than limonene. These findings suggest that S.7942 is better suited to produce sesquiterpenes than monoterpenes. Also interestingly, higher levels of terpenes were produced by S.7942 and S.7002 expressing a terpene-synthase gene from both a RSF1010-derived replicating plasmid and a neutral chromosomal site, as compared to ei-ther the plasmid alone or the chromosome alone. These results suggest that in both cyanobacteria the production of terpenes is more limited by the activity of terpene synthases than the abondance of terpene precursors. Finally, higher levels of terpenes were produced by S.7002 growing on urea (a frequent pollutant) as compared to nitrate (or ammonium) the standard nitrogen sources for cyanobacteria (more expensive than urea).

Inteins, often referred to as protein introns, are highly mobile genetic elements that invade conserved genes throughout the tree of life. Inteins have been found to invade a wide variety of key genes within actinophages. While in the process of conducting a survey of these inteins in actinophages we discovered that one protein family of methylases contained a putative intein, and two other unique insertion elements. These methylases are known to occur commonly in phages as orphan methylases (possibly as a form of resistance to restriction-modification systems). We found that the methylase family is not conserved within phage clusters and has a disparate distribution across divergent phage groups. We determined that two of the three insertion elements have a patchy distribution within the methylase protein family. We also found that the third insertion element is likely a second homing endonuclease, and that all three elements (the intein, the homing endonuclease, and what we refer to as the ShiLan domain) all have different insertion sites that are conserved in the methylase gene family. Furthermore, we find strong evidence that both the intein and ShiLan domain are partaking in long distance horizontal gene transfer events between divergent methylases in disparate phage hosts within the already dispersed methylase distribution. The reticulate evolutionary history of methylases and their insertion elements reveals high rates of gene transfer and within-gene recombination in actinophages.

Apis cerana and Apis mellifera, are very important honey species for agriculture in Asian countries. In recent decades, A. cerana populations have sharply declined in all Asian countries as a result of Sacbrood Virus infection and have now recovered to their original size. It can change the genetic structure of local populations of A. cerana. We used the nuclear gene Vitellogenin VG to assess the genetic structure of local populations of A. cerana and the signature of adaptive selection. We performed a population genetic analysis of the honey bees A. cerana from South Korea in comparison with A. cerana samples from Russia, Japan, Nepal, and China. The sequences of the gene VG of a closely related honey bee species, A. mellifera, from India and Poland were used as outgroup samples. A comparative analysis of northern and southern A. cerana populations was performed. The signatures of positive adaptive selection were found in the local population of A. cerana. We performed the Tajima's neutrality D test for A. cerana populations from different local populations based on the gene VG exon sequences. All A. cerana populations showed signs of population size expansion following the possible recent decline in population sizes. The local populations of A. c. koreana were subdivided according to their geographical distribution into southern, northern, and central Korean clusters. The gene VG exon sequences can be used as informative markers for monitoring the changes in genetic structure and adaptation to the environment processes in A. cerana populations.

Flood routing in flood forecasting issue, calculation the height of flood bands, determining the river boundaries, and estimation of protective facilities for flood –exposed building is applicable. In many cases, due to the lack of measuring stations, the status of the upstream flood generating hydrograph is not known. The purpose of this study is to present an integrated method comprising of an optimization model and a hydrodynamic numerical model for flood modeling to determine the upstream hydrograph using the provided hydrograph at the downstream measuring station of a river. The routing procedure consists of three steps: (1) generating a hypothetical upstream hydrograph using genetic algorithm method; (2) hydrodynamic modeling using a numerical simulation model for flood routing according to the hypothetical hydrograph which is generated in the first step; (3) compare the calculated and observed hydrograph in downstream by using a fitness function. This recommended procedure was named as Reverse Flood Routing Method (RFRM) and was then applied to Karun River, the largest river in Iran. Comparing the generated upstream hydrograph by the RFRM model with the corresponding measured hydrograph at Ahvaz hydrometric station, as an ungauged river location, shows the high accuracy of the recommended model in this study.

Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen frequently associated with acute diarrhea in children and travelers to endemic regions. EAEC was found the most prevalent bacterial diarrheal pathogen from hospitalized Bolivian children less than five years of age with acute diarrhea from 2007 to 2010. Here, we further characterized the epidemiology of EAEC infection, virulence genes, and antimicrobial susceptibility of EAEC isolated from 414 diarrheal and 74 non-diarrheal cases. EAEC isolates were collected and subjected to a PCR-based virulence gene screening of seven virulence genes and a phenotypic resistance test to nine different antimicrobials. Our results showed that atypical EAEC (a-EAEC, AggR-negative) was significantly associated with diarrhea (OR, 1.62, 95% CI, 1.25 to 2.09, P < 0.001) in contrast to typical EAEC (t-EAEC, AggR-positive). EAEC infection was most prevalent among children between 7 - 12 months of age. The number of cases exhibited a biannual cycle with a major peak during the transition from warm to cold season (April – June). Both typical and a-EAEC infections were graded as equally severe; however, t-EAEC harbored more virulence genes. aap, irp2, and pic were the most prevalent genes. Surprisingly, we detected 60% and 52.6% of multidrug resistance (MDR) EAEC among diarrheal and non-diarrheal cases. Resistance to ampicillin, sulfonamides, and tetracyclines was most common, being the corresponding antibiotics, the ones that are frequently used in Bolivia. Our work is the first study that provides comprehensive information on the high heterogenicity of virulence genes in t-EAEC and a- EAEC and the large prevalence of MDR EAEC in Bolivia.

Studies on evolution have made significant progress in multiple disciplines, but evolutionary theories remain scattered, complicated, elusive, and controversial. To address this issue, a novel evolutionary theory is deduced from thermodynamics in this article. As per the formula of Gibbs free energy, carbon-based entities (CBEs) on Earth tend to absorb more energy. This is the evolutionary driving force leading to organic synthesis of higher-hierarchy CBEs (HHCBEs). The organic synthesis raises the amount of HHCBEs and increases the structural complexity and hierarchy of CBEs. Increased structural complexity and hierarchy spontaneously offer complicated functions to HHCBEs. Genetic mutations, epigenetic changes, and uninheritable variations provide diversified HHCBEs for natural selection which is redefined as survival of the fit and elimination of the unfit, leading to increase of diversity and fitness of HHCBEs. Order in biology resulting from permanent natural selection is largely contrary to order in physics. Natural selection acts on the overall fitness involving all traits through the co-action of positive selection and negative selection. Natural selection can establish biological traits in short geological periods. Different combinations of traits can lead to sympatric speciation targeting the same niche. Altruism, collaboration, and obeying rules with balanced freedom are all important throughout the CBE evolution, which harbors three overlapping phases including chemical evolution (abiogenesis), biological evolution, and group evolution. Altogether, this theory termed the CBE evolutionary theory (CBEET) suggests that evolution which favors fitness and diversity is driven hierarchy-wise by energy. It reveals the driving force of evolution and reestablishes the key role of natural selection. It integrates with advances from multiple disciplines and provides simple and rational answers to some evolutionary conundrums. It removes several elusive or erroneous views including the one regarding negative entropy. It bridges natural sciences and social sciences and sheds novel insights into harmonious development of human society.

Owing to the time-varying characteristics and nonlinearities of industrial processes, control has higher difficulties and results in challenges for advanced technology. In this paper, a self-tuning controller that includes a nonlinear proportional-integral-derivative (NPID) control function as well as a self-tuning function is proposed for first-order plus time delay (FOPTD) process control. The NPID control function is implemented using the nonlinear PID controller whose optimum parameters are adapted by a neural network (NN). The self-tuning function is able to identify the process dynamics using a short period of process behavior and tune NPID parameters based on the identified parameters. The advantage of the proposed method is validated with a set of simulation works on three processes and the comparison results are presented.

Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However some critical issues related to ctDNA assays should be taken in consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC) qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of cfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensively resistant (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definition. Sub-lineage 4.3 (52%) was the most frequent genotype and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected 20 novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. Cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug-resistance prediction, presenting the best accuracy values to five of nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) and genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil, genetic and clinical data correlations and demonstrating its utility for surveillance efforts for spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

In this report we describe the case of a healthy, young, athletic woman who developed acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma (LBL) after receiving the second dose of the Pfizer/BioNTech modified mRNA (modRNA) COVID-19 genetic vaccine (marketed as Comirnaty^®). The first dose of the genetic vaccine did not appear to illicit any noticeable side effects, but within 24 hours of the second dose the patient suffered widespread and intensifying bone pain, fever, vomiting, and general malaise. Due to the persistence of the symptoms, the patient underwent a series of tests and examinations including a full laboratory workup, a consult with a clinical immunologist and rheumatologist, a Positron Emission Tomography (PET) imaging, as well as an osteomedullary biopsy. These together led to a definitive diagnosis of ALL. A time interval of 16 weeks from the second vaccination to the diagnosis of cancer was noted. Several similar cases with identical pathology which developed after the modRNA COVID-19 vaccination, are described in case reports in the scientific literature. The massive and indiscriminate use of genetic vaccines to fight COVID-19 is raising serious concerns about their safety and about the technology platform as a whole for this purpose. Growing evidence is accumulating regarding the biodistribution and persistence of the modRNA which can reach, thanks to the lipid nanoparticles, a multitude of tissues and organs of the body, including the bone marrow and other blood-forming organs and tissues. Moreover, there is evidence that the modRNA vaccines display a particular tropism for the bone marrow, influencing the immune system at multiple levels and being able to trigger not only autoimmune-based pathologies, but also neoplastic mechanisms. The aim of this article is to assess, on the basis of the available scientific literature, the risk of developing haematopoietic cancers after modRNA vaccination, and to investigate the potential genetic mechanisms involved in the pathogenesis of disease.

Efficient fixed crane position analysis is critical in precast buildings construction to maximize lifting efficiency for precast elements. The primary objective is to minimize the travel distances of fixed cranes, thereby enhancing operational efficiency and cost control. This involves strategically reducing the distances between the transport truck parking, where elements are stored, the fixed crane, and the construction installation point. Despite its significance, existing studies often overlook the dynamic movement efficiency of transport trucks, particularly when dealing with multiple transport trucks and various models of fixed cranes, rendering the opti-mization of this scenario a challenging NP-hard problem susceptible to combinatorial explosion. This study presents a novel mathematical model leveraging the Genetic Algorithm (GA). The model aims to solve optimal model and position of fixed cranes, along with identifying ideal positions for transport truck parking. The study's methodology is validated and demonstrated through a project case study. Comparative analyses between the proposed model and the original planning underscore a noteworthy 6% reduction in both duration and costs when lifting elements directly from transport trucks, as opposed to establishing an on-site stock yard. Furthermore, the developed GA exhibits a substantial improvement in final solutions, achieving a remarkable 30% reduction in both operational duration and costs. This research contributes valuable insights into fixed crane position analysis of precast building construction, providing foundation for enhanced operational efficiency and cost-effectiveness in the industry.

This review article delves into the pivotal role of DNA in advancing criminal investigations, presenting a comprehensive analysis of its impact on modern justice systems. DNA, as the genetic blueprint of individuals, has revolutionized forensic science, augmenting the accuracy and reliability of criminal investigations. This study explores the historical evolution of DNA analysis, from its initial discovery to the development of sophisticated techniques like polymerase chain reaction (PCR), short tandem repeat (STR) profiling, and next-generation sequencing (NGS). The article elucidates the intricate process of DNA collection, preservation, and analysis, highlighting its significance in establishing identity, proving guilt or innocence, and resolving cold cases. The utilization of DNA databases and international cooperation in cross-border investigations are also examined, emphasizing their contributions to solving complex criminal cases. Moreover, the ethical, legal, and privacy considerations surrounding DNA usage in criminal justice are critically evaluated. Through a comprehensive literature review, this article synthesizes empirical evidence showcasing how DNA evidence has exonerated wrongfully convicted individuals and provided closure to victims' families. It further elucidates how technological advancements have extended DNA analysis to trace evidence, touch DNA, and forensic genealogy, thereby broadening its application in criminal investigations.

Delve into the dynamic realms of neuroscience, neurology, and psychiatry with this groundbreaking editorial, unveiling the intricate mechanisms of brain function and dysfunction. Explore the latest advancements in molecular biology, genetics, epigenetics, pharmacology, and neuroimaging that are revolutionizing our understanding of neurological and psychiatric disorders. Uncover the challenges and gaps in translating cutting-edge research into practical clinical applications, aiming to enhance the lives of patients and their families. Discover the pivotal role of neuroplasticity in reshaping the brain's adaptability throughout life, alongside the promising potential of non-invasive brain stimulation techniques like transcranial magnetic stimulation and transcranial direct current stimulation. Embark on a journey of innovation and collaboration as researchers and clinicians strive to bridge the gap between bench and bedside, offering hope for improved diagnosis, prevention, and treatment of complex neurological and psychiatric conditions. Join us in this exploration of transformative ideas and novel interventions that hold the key to a brighter future for individuals and society.

Previous studies found high but very variable levels of tetranor-PGEM and PGD-M (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF), which correlated with the severity of the CF transmembrane receptor (CFTR) genetic alteration. This study aims to assess the potential role of cyclooxygenase (COX)-1 and COX-2 genetic polymorphisms in the variability of PG production, and determine the potential role of PG metabolites as markers of symptoms severity and imaging findings. Thirty healthy subjects and 103 pwCF were included in the study. Clinical and radiological CF severity was evaluated using clinical scoring methods and the extent of bronchiectasis and air trapping were assessed by chest computed tomography (CT). Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. The presence of variants in the COX-1 gen (PTGS1 639 C>A, PTGS1 762+14delA, and COX-2 gen: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were analysed. PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in healthy controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Taken together, the present study suggests that urinary PG level testing can be used as a biomarker of CF severity. We found no relationship between COX-1 and COX-2 genetic polymorphisms in the variability of PG production.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving liver, pancreas and brain in the con-text of cystic manifestations, while vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remain the main feature of the disease, thanks to new generation therapies, early diagnosis and better management of kidney related problems, a new wave of complications must be faced from clinicians who treated polycystic patients. Involvement of the liver represents the most prevalent extrarenal manifestation and grows importance in symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there’s still de-bate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset among polycystic patients leading to frequent cardiovascular complications. Although cardiac valvular abnormali-ties is a frequent complication, it rarely leads to relevant problems in the clinical history of polycystic pa-tients. One of the new relevant aspects concern bone disorders, that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of art” among extrarenal mani-festation of ADPKD.

Herein, we applied DNA Barcoding for the genetic characterization of Sideritis syriaca subsp. syriaca (Lamiaceae; threatened local Cretan endemic plant), using seven molecular markers of cpDNA. Five fertilization schemes were evaluated comparatively in a pilot cultivation in Crete. Chemical fertilizers (ChF), integrated nutrient management fertilizers (INM) and two biostimulants were utilized (foliar and soil application). Plant growth, leaf chlorophyll fluorescence and colour were assessed, and leaf content of chlorophyll, key antioxidants (carotenoids, flavonoids, phenols), and minerals were evaluat-ed. Fertilization regime did not affect leaf colour but induced distinct differences in leaf shape altering quality characteristics. INM-foliar and ChF-soil application promoted yield, without affecting tissue water content or biomass partitioning to inflorescences. ChF-foliar application was the most stimulato-ry treatment for enhanced antioxidant compound content, while INM-biostimulant was the least effec-tive one. In conclusion, adverse fertilization options appear as optimal when considering yield or anti-oxidant compound content. New DNA sequence datasets for the plastid regions of petB/petD, rpoC1, psbK-psbI and atpF/atpH have been deposited in the GenBank for S. syriaca subsp. syriaca while the mo-lecular markers rbcL, trnL/trnF, psbA/trnH were compared to those of another 15 Sideritis species re-trieved from the GenBank, constructing a phylogenetic tree to show their genetic relatedness.

The development of modern genomic tools has sped up the breeding program of food crops. More recently, genomic resources are being developed for tropical forages and will be key resources for developing climate resilient high yielding forage varieties. In this study, we present a genome-wide association study for biomass yield and feed quality traits in buffel grass (Cenchrus ciliaris L. aka Pennisetum ciliare L.,). Genome-wide markers generated using the DArTSeq platform and mapped onto the reference genome of Setaria italica were used for the genome-wide association study. The results revealed several markers associated with biomass yield and feed quality traits. A total of 78 marker trait associations were identified with R2 values ranging from 0.138 to 0.236. The marker trait associations were distributed across different chromosomes. Of these associations, the most marker trait associations (23) were observed on Chr9, followed by Chr5 with 12. The fewest number of marker trait associations were observed on Chr4 with 2. In terms of traits, 17 markers were associated with biomass yield, 24 with crude protein, 26 with TDN, 14 with ADF, 10 with NDF and six with DMI. Twenty of the identified markers were associated with at least two traits. The identified marker trait associations provide a useful genomic resource for future improvement and breeding of buffel grass.

In the context of globalization One Health enables and concurs to the achievement of Global Health. One Health approach involves wide knowledge and understanding of its critical factors, next to an adequate implementation, also in farm animal sector. Moreover, animal farming and breeding shows particularities depending on country. Therefore, well-defined and specific strategies are still needed to be developed and adapted to the current conditions found in various countries for ensuring a well implementation, thus driving to better and healthier global outcomes and security. This paper will explore the One Health status in Romania, highlighting the current progress registered until now and the future perspectives based on its potential, in the context of the livestock farming framework and challenges. Our findings may help to disclose the challenges of putting in practice One Health in Romania, alongside to the pathways showing potential to enhance sustainability in livestock farming.

The feasibility of recovering bioactive antioxidants from Phyllantus emblica leaves using ethanol -water mixture (0 – 100%) and heat-assisted extraction technology (HAE-T) was investigated in this present study. To this effect, the process parameter of operating temperature (OT: 30 -50 oC), solid -to-liquid ratio (S:L: 1:20 - 1:60 g/mL) and extraction time (ET: 45 - 180 min) were investigated on the extract total phenolic content (TPC, mg GAE/g d.w), yield (EY, %) and antioxidant activity (μM AAE/g d.w) by employing the Box-Behnken experimental design (BBD) available in response surface methodology (RSM). Multi-objective process optimization using the desirability function algorithm to determine set of process variables that simultaneously optimize process responses of TPC, EY and AA was also investigated. The recovery process was thereafter modeled with BBD-RSM and multi gene genetic programming (MGGP) algorithm and model reliability assessment via Monte Carlo simulation were conducted for the best performing set of models for predicting TPC, EY and AA values. The HPLC characterization of the recovered extract was carried out to ascertain the phenolic compound constituents of the Phyllantus emblica leaf extract. The 50% ethanol solution was found to be the best for the optimal extraction of antioxidants from Phyllantus emblica leaves. The HAE-T was suitable for recovering bioactive extract from Phyllantus emblica leaves and investigated process parameters have impacts on the recovery process. The process parameters that simultaneously gave the optimum EY of 21.6565%, TPC of 67.116 mg GAE/g and AA of 3.68583 µM AAE/g were OT of 41.61 oC, S:L of 1:60 g/mL and ET of 180 min. The HPLC extract profiling revealed that the bioactive constituents present in the recovered extract were betulinic acid, gallic acid, chlorogenic acid, caffeic acid, ellagic acid, and ferulic acid. Both the developed BBD-RSM and evolved MGGP-based models predicted the observed process response of TPC, EY and AA satisfactorily with BBD-RSM models marginally better in their predictions. The reliability results showed that the BBD-RSM models predicted TPC, EY and AA values with high certainty of 99.985%, 97.569% and 98.661%, respectively.

The cultivation of Hevea brasiliensis, the primary commercial source of natural rubber, is strongly impacted by South American Leaf Blight (SALB) disease, caused by the fungus Pseudocercospora ulei. Various management strategies have been implemented, including the selection of resistant genotypes and the identification of escape zones. This study evaluated the growth, early yield, and resistance to SALB of nine Colombian elite genotypes from the ECC-100 series and IAN 873 clone (control) in a large-scale clone trial in a low SALB pressure zone in the Colombian Amazon, 2017 - 2020. Favorable early performance was evident, although there was a significant increase in the severity and sporulation of P. ulei over time, especially in the ECC 35, ECC 60, and IAN 873 genotypes. However, these scores represented a low susceptibility. Genotypes with higher resistance to SALB demonstrated greater growth and early yield compared to higher susceptible genotypes. The ECC 64, ECC 73, ECC 90, ECC 25, and ECC 29 genotypes were more desirable in low SALB pressure zones due to their higher resistance and early performance. It is important to highlight that this research contributes to the selection of new SALB-resistant Colombian genotypes of H. brasiliensis in the growth stage. Therefore, it is necessary to evaluate their productivity in the mature stage and long-term resistance to SALB, before recommending and promoting their commercial adoption in the Colombian Amazon.

The advancement of technology and the availability of specialized digital signal processing chips have made digital filter design and implementation more feasible in a variety of fields, including biomedical engineering. This paper makes two key contributions. First, it uses a genetic algorithm to optimize the coefficients of Finite Impulse Response (FIR) filters. Second, it conducts a case study on using genetic algorithms to optimize FIR filters for electrocardiogram (ECG) biomedical signal noise removal. The goal of the proposed filter design approach is to achieve the desired signal bandwidth while minimizing the side lobe level and eliminating unwanted signals using a genetic algorithm. The results of the comprehensive analysis of the impact of different genetic operators show that the genetic algorithm-based filter outperforms conventional filter designs.

Scrub typhus (ST) is one of the most neglected tropical diseases, a leading cause of acute undifferentiated febrile illness in areas of the ‘tsutsugamushi triangle’, diagnosed frequently in South Asian countries. The bacteria Orientia tsutsugamushi is the causative agent of the disease, which enters to human body through the bite of trombiculid mite (Chigger) of the genus Leptotrombidium deliense.The diagnosis of the disease becomes challenging as its early symptoms mimic other febrile illnesses like dengue, influenza, and corona viruses. Lack of rapid, reliable, and cost-effective diagnostic methods further complicates the identification process. Northeast India, a mountainous region with a predominantly rural tribal population, has witnessed a resurgence of scrub typhus cases in recent years. Various ecological factors, including rodent population, habitat characteristics, and climatic conditions, influence its prevalence. Entomological investigations have confirmed the abundance of vector mites, highlighting the importance of understanding their distribution and the probability of transmission of scrub typhus in the region. Proper diagnosis, awareness campaigns, and behavioral interventions are essential for controlling scrub typhus outbreaks and reducing its impact on public health in Northeast India. Further research and community-based studies are necessary to accurately assess the disease burden and implement effective prevention strategies.

Bibliometric studies on inherited metabolic diseases(IMDs) didn't exist in the literature.Our research aims to conduct a bibliometric study to determine the current status,trending topics,and missing points of publications on IMDs.Between 1968-2023, we conducted a literature search with keyword "inherited metabolic disease" in the SCOPUS-database.We included research articles in medicine written in English,published in the final section.We created our data pool using VoSviewer, SciMAT, and Rstudio software programs for bibliometric parameters of the articles that met the inclusion criteria.We performed bibliometric analysis of the data with R-package "bibliometrix" and BibExcel programs.We included 2702 research articles published on IMDs.Top three countries that have written the most articles in this field are; USA(n= 501), United Kingdom(n=182), and China(n= 172).The most preferred keywords by the authors were;newborn screening(n=54), mutation(n=43), phenylketonuria(n=42), children(n=35), genetics(n= 34) and maple syrup urine disease(n=32).Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective showing that molecular and genetic studies in inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

In this work, we present a new way to study the genetic code mathematical and chemical structure, based on the use of mathematical computations involving some few recently designed Fibonacci-like sequences, the “seeds” (“initial conditions”) of which are chosen according to the chemical and physical data of the three amino acids serine, arginine and leucine, playing a prominent role in a recent symmetry classification scheme of the genetic code. It appears that these mathematical sequences, of the same kind as the famous Fibonacci series, apart from their usual recurrence relations, are highly interwinned by many useful linear relationships. Using these sequences and also various sums or linear combinations of them, we derive several physical and chemical quantities of interest, as the number of total coding codons, 61, obeying various degeneracy patterns, the detailed number of hydrogen atoms, the detailed number of atoms (H/CNOS) and the integer molecular mass (or nucleon number), in the side chains of the 61 “amino acids”, also in various degeneracy patterns, in agreement with those described in the literature. Also, unexpectedly but interestingly, we find, as a by-product, an accurate description of the very chemical structure of the four ribonucleotides uridine monophosphate (UMP), cytidine monophosphate (CMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP), the building blocks of RNA whose groupings, in three units, constitutes the triplet codons. In summary, we find a full mathematical and chemical connection with the “ideal sextet’s classification scheme” mentioned above as well as with several others, notably, the Findley-Findley-McGlynn symmetrical classification. We organize the content of the text in such a way that, besides the presentation of several new research results, it has also an educational dimension. The paper could therefore be read and the computations easily worked out, also by non-experts with mathematical background.

Lithium batteries are widely used due to their advantages such as high energy density, stable performance, low pollution, and long recyclable life. Accurate SOC estimation is important for the use of lithium batteries. To address the problem of low accuracy of SOC estimation by traditional methods, this paper proposes a joint method of fractional order robust unscented Kalman filter (FORUKF) and robust unscented Kalman filter (RUKF) to estimate SOC. The method is based on a fractional order model (FOM) that combines the unscented transformation (UT) technique, the H∞ observer and the joint estimator. Specifically, an adaptive genetic algorithm (AGA) was first used to identify the parameters of the FOM for lithium batteries and to verify the accuracy of the model. Estimation and updating of the ohmic resistance R0 and the capacity QN in the model in real-time by RUKF and then estimation of the SOC by FORUKF. Finally, the accuracy of FORUKF-RUKF was verified under the Federal Urban Driving Schedule (FUDS), US06 Highway Driving Schedule and Beijing Dynamic Stress Test (BJDST). According to the results, the FORUKF-RUKF estimated SOC was found to have better accuracy and robustness than the RUKF, FOUKF and EKF.

The winged bean is an underutilized legume that has the potential to contribute to nutrition and food security globally, especially in sub-Saharan Africa (SSA). However, very little research attention is paid to exploiting its full potential due to a lack of adequate knowledge of the existing genetic diversity in the available winged bean germplasm. To bridge this gap, seed morphometric and selected agro-morphological traits which are crucial for yield and seed quality determination in crop plants were used to assess the genetic diversity of thirty accessions of winged bean sourced from the Gene bank of the International Institute of Tropical Agriculture (IITA), Ibadan. The thirty winged accessions were evaluated under field trials at three agro-ecological zones in Nigeria. The agro-morphological data as well as the seed morphometric dataset obtained from a Multi-Spectral Imaging (MSI) system were subjected to Analysis of Variance (ANOVA), Principal Component (PC) analysis, cluster analysis, and correlation analysis. Significant differences (p &lt; 0.05) were observed among the accessions for all measured traits. The first three PCs accounted for 93% of the variation observed among the accessions for all measured traits. Accessions were grouped into three clusters based on the agro- morphological traits and three clusters under the MSI system. Seed yield per plant had the highest estimates of significant positive correlation with hundred seed weight, pod weight per plant, etc. at both phenotypic and genotypic levels. TPt-31 had the highest seed yield per plant, pod weight per plant, and early maturity while TPt-7 had an extended flowering and maturity period, the highest number of pods per peduncle and pods per plant as well as the lowest seed yield. These accessions could serve as a good resource for future winged bean improvement programs. The result also confirmed that the MSI system is an invaluable tool for discriminating among accessions of the same crop species.

The literature has well established prestressing in concrete beams and its calculation procedures. However, its use in composite steel-concrete beams has increased despite main normative codes lacking a specific approach for it. Designers must, in most cases, combine the available criteria to calculate the standards of steel and reinforced concrete structures. This study aimed to formulate this optimization problem and analyze CO2 emissions for the optimal design of composite steel-concrete beams with external prestressing. The design variables for the optimization problem include cross-section of laminated or welded profiles, slab height, characteristic strength of concrete to compression, and number of tendons. We obtained a solution for the optimization problem via a genetic algorithm (GA) and a particle swarm optimization one (PSO). Comparative analysis with experimental example and with optimization problem of prestressed steel beam are performed. An parametric analysis to several spams is performed, which enabled to evaluate the factors that most impact CO2 emissions. According to results, the chosen algorithms effectively obtained solutions for the problem, and PSO usually provided better results than GA. Regarding the final solution composition, steel contributes the most to emissions, welded profiles provided better solutions than laminated ones, and laminated spans of up to 17.5m and welded ones up to 27.5m dispensed with tendons.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

The contribution of genetic and environmental factors to the pathophysiology of cerebral aneurysms in monozygotic twins is under-reported and presents ambiguous arguments. The morphology and hemodynamics of neurovascular arteries in a pair of monozygotic twins (MTs) were investigated to reveal the underlying mechanisms. Four arterial models were reconstructed for the twin A-right brain and left brain, twin B-left brain, and B-left brain without anterior cerebral arteries based on preclinical scanned information. Subsequently, the dimensions, configurations and outlined curves of the three-perspective geometries were compared between the MTs. Adopting an in-vitro validated numerical cerebral aneurysm model, hemodynamic patterns were investigated and compared in the MT models, respectively. Morphological comparisons of the MTs show the size and shape of cerebral arteries exist significant differences, despite of the expected genetic similarities. These differences can be attributed to variations during embryological development and external environmental influences. Qualitatively and generally, numerical results indicate the MTs have some hemodynamic similarities (e.g., time-averaged pressure (TAP) distributions (~13400 Pa), and oscillatory shear index (0~0.49), but present significant differences in specific local arteries due to morphological variances. Specifically, the difference in the volumetric blood flow rate in corresponding arteries between the MTs is from 16% (smallest) in anterior choroidal artery (AChA) to 221% (largest) in the ophthalmic artery (OphA), varying with specific compared arteries. Also, the registered hemodynamic indicators, such as the maximum time-averaged wall shear stress (TWSS) (53.6 Pa vs. 37.8 Pa), and different local OSI distributions were observed between the MTs. The findings revealed that morphological variations in MTs could be generated by embryological and environmental factors, thus assuming they share the identical morphology in cardiovascular and neurovascular systems may lead to significant misevaluations in hemodynamics quantifications and further lesions.

The evolutionary systems (ES) include software applications that solve problems using heuristic methods instead of the deterministic ones. The classical computing used for ES development involves random methods to improve different kinds of genomes. The mappings of these genomes lead to individuals that correspond to the searched solutions. The individual evaluations by simulations serve for the improvement of their genotypes. Quantum computations, unlike the classical computations, can describe and simulate a large set of individuals simultaneously. This feature is used to diminish the time for finding the solutions. Quantum Petri Nets (QPNs) can model dynamical systems with probabilistic features that make them appropriate for the development of ES. Some examples of ES applications using the QPNs are given to show the benefits of the current approach.

Maize (Zea mays subsp. mays) is the staple food crop in the world. In this study, multi-layer perceptron (MLP), support vector machine (SVM), genetic algorithm-based multi-layer perceptron (MLP-GA), and genetic algorithm-based support vector machine (SVM-GA) hybrid artificial intelligence algorithms were used for the prediction of drought tolerance and stress tolerance indices in teosinte maize lines. Correspondingly, the gamma test technique was applied to determine efficient input and output vectors. The potential of developed models was evaluated based on statistical indices and graphical representation. Results of gamma test based on the least value of gamma and standard error indices show that day of anthesis (DOA), day of silking (DOS), yield index (YI), and gross yield per plant (GYP) information vector arrangements were determined as efficient information vector combination for drought-tolerant index (DTI) as well as the stress-tolerant index (STI). The results of MLP, SVM, MLP-GA, and SVM-GA algorithms were compared based on statistical indices and visual interpretation that have satisfactory for prediction of the drought-tolerant index and stress-tolerant index in maize crop. It has also seemed that genetic algorithm-based hybrid models (MLP-GA and SVM-GA) were found a better prediction of the drought-tolerant index and stress-tolerant index in maize crop. Similarly, the SVM-GA model has the highest potential to forecast the DTI and STI in maize crops as compared to MLP, SVM, MLP-GA models.

The global climate change mitigation efforts have increased the efforts of national government to incentivize local households in adopting individual renewable energy as a mean to help reduce the usage of electricity generated using fossil fuels and to gain independence from the grid. Since the majority of residential generation is made by PV panels that generate electricity at off-peak hours, the optimal management of such installations often considers local storage that can defer the use of locally generated electricity at later times. On the other hand, the presence of distributed generation can affect negatively the operating conditions of low-voltage distribution networks. The energy stored in batteries located in optimal places in the network can be used by the utility to improve the operation of the network. This paper proposes a metaheuristic approach based on a Genetic Algorithm that considers three different scenarios of using energy storage for reducing the losses in the network. Prosumer and network operator priorities can be considered in different scenarios inside the same algorithm, to provide a comparative study of different priorities in storage placement. A case study performed on a real distribution network provides insightful results.

Cancer is fundamentally a disease of perturbed genes. Although many mutations can be marked in the genome of a cancer or transformed cell, the initiation and progression were shown to be driven by only a few mutational events viz. driver mutations that progressively govern and execute the functional impacts. The driver mutations are thus believed to dictate and dysregulate the subsequent cellular proliferative function/decisions thereby producing a cancerous state. Therefore, identifying the driver events from the genomic alterations in a patient’s cancer cell gained large attention recently for designing better targeting therapies towards paving way for the precision cancer medicine. With rolling advancements in high-throughput omics technologies, analysis of genetic variations and gene expression profiles for cancer patients has become a routine clinical practice. However, it is anticipated that protein structural alterations resulting from such driver mutations can provide more direct and clinically relevant evidence of disease states than genetic signatures alone. This review comprehensively discusses various aspects and approaches that have been developed for the prediction of cancer drivers using genetic signatures and protein structures, and their potential application in developing precision cancer therapies.Keywords:

The method of doublet frequency distance (DFD-) maps was applied, here, for visualization of DNA sequence structures of yeast chromosomes. The colour scale “rainbow” of the Octave programming tool is well suited for such visualization. The DFD-maps are generated by comparison of the differences in the number of all base doublets in a shifting frame with all other positions of this frame in a regarded DNA sequence section. This procedure can be applied from DNA-sections of between a few hundred bases (bps) up to a complete chromosome with a million or more bps. An orthogonal DFD-map pattern dominates all chromosomes and its parts. It can be interpreted by a large number of successive mutation events during evolution. In contrast, diagonal patterns indicate duplications of sequence sections and multiple tandem repeats. These periodic structures are found in several chromosomes and are more or less regular or noised. The larger tandem repeat in the subtelomeric region of chromosome 12 presents a characteristic example of a nested multiple-repeat structure. Its pattern in the DFD-map illustrates obviously a temporal order of duplication and mutation events leading to a hierarchical sequence architecture.

We designed a novel growth controller regulated by feeding of an unnatural amino acid, Nε-benzyloxycarbonyl-L-lysine (ZK), using a specific incorporation system at a sense codon. This system is constructed by a pair of modified pyrrolisyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl). Although ZK is non-toxic for normal organisms, the growth of Escherichia coli carrying the ZK incorporation system was inhibited in a ZK concentration-dependent manner without causing rapid bacterial death, presumably due to generation of non-functional or toxic proteins. The extent of growth inhibition strongly depended on the anticodon sequence of the tRNApyl gene. Taking advantage of the low selectivity of PylRS for tRNApyl anticodons, we experimentally determined the most effective anticodon sequence among all 64 nucleotide sequences in the anticodon region of tRNApyl gene. The results suggest that the ZK-regulated growth controller is a simple, target-specific, environmental noise-resistant and titratable system. This technique may be applicable to a wide variety of organisms because the growth inhibitory effects are caused by “informational disturbance”, in which the highly conserved system for transmission of information from DNA to proteins is perturbed.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

This paper questions the potential shift of reproduction towards assisted reproductive technologies due to benefits provided by genetic manipulation of embryos. In order to examine the viability of such a shift and its implications from a regulatory perspective, we relied on two panels of experts from Israel and Spain, using the Delphi method and a series of in-depth interviews. We anticipate, at a first stage, a continuous-steady growth in the use of IVF, supplemented by preimplantation genetic diagnosis and the introduction of CRISPR/Cas. At a second stage, attracting a growing share of fertile people would require developments in genomics. While it is unclear whether these developments will fully materialize, they could be replaced by technoscientific imaginaries generating perceived benefits. We conclude that the regulation of reproductive genetics is becoming more critical and complex. The aim should be to ensure good practices and equity, while providing more information to the public. A broad and inclusive societal debate may overcome the difficulty of drawing a clear line between medical uses and non-medical uses of genetic selection and engineering and may contribute to finding the right balance between allowing autonomous decisions of patients and protecting the public interest.

In addition to the canonical loss-of-function mutations, mutations in proteins may additionally result in gain-of-function through the binary activation of cryptic ‘structural capacitance elements’. Our previous bioinformatic analysis allowed us to propose a new mechanism of protein evolution - structural capacitance – that arises via the generation of new elements of microstructure upon mutations that cause a disorder-to-order (DO) transition in previously disordered regions of proteins. Here we propose that the DO transition is a necessary follow-on from expected early codon-anticodon and tRNA acceptor stem-amino acid usage, via the accumulation of structural capacitance elements - reservoirs of disorder in proteins. We develop this argument further to posit that structural capacitance is an inherent consequence of the evolution of the genetic code.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

The current work addresses the control of two-input two-output (TITO) Wood and Berry model of a binary distillation column. The controller design problem is formulated in terms of multivariable H_∞ control synthesis. The controller structure takes the form of simplest static output feedback (SOF) control. The controller synthesis is performed using a hybrid approach of blending linear matrix inequalities (LMI) and genetic algorithm (GA). The performance of the static output feedback controller is compared with three other controllers designed for Wood and Berry model available in the literature. The first simulation study is performed for the case of tracking a unit step command in the presence of a step change in output disturbance. A second simulation study is performed for rejecting a change in sinusoidal output disturbance.

In order to improve the performance of the draft tube in hydraulic turbine, a multi–objective optimization method for the draft tube is developed by combining the design of experiment (DOE), the radial basis function (RBF) and the non–dominated sorting genetic algorithm (NSGA–II) in this paper. The geometrical design variables of the median section in the draft tube and the cross section in its exit diffuser are considered as design parameters in this optimization, which objective function is to maximize the pressure recovery factor (Cp) and minimize the energy loss coefficient (ζ). The limited numbers of design matrix required for the shape optimization of the draft tube is generated by optimal Latin hypercube (OLH) method of the DOE technique, of which performances are evaluated through computational fluid dynamic (CFD) numerical simulation. For reducing of the computational consumption, the approximate model is used based on the RBF. The Pareto optimal solutions are finally performed using the NSGA–II for obtaining the best geometrical parameters of the draft tube. The optimization result of the draft tube shows a marked performance improvement over the original, which verifies the theoretical validity and feasibility of the proposed method in this paper.

Ultrasound, as mechanical waves with frequencies exceeding 20 thousand hertz, has found wide applications in medicine, physiotherapy, and more recently in agriculture. This study aimed to investigate the impact of ultrasound on potato yield and its parameters, particularly on seed potato yield, quantity, mass, and multiplication coefficient of potato tubers. The research was based on a three-year field experiment, utilizing the randomized block design in a split-split-plot arrangement, in the central-eastern region of Poland. The primary factor were technologies: a) technology with employing ultrasonic pre-planting treatment, b) traditional cultivation without this treatment. The secondary factors were potato varieties. Sonication of tubers was conducted using a bath-type ultrasonic device equipped with piezoe-lectric transducers. Results revealed a significant influence of cultivation technology, cultivar, and weather conditions on seed tubers yield, quantity, and multiplication coefficient of potato tubers. However, genetic traits of the examined varieties and random factors significantly affected the individual seed tuber mass and the number of shoots emerging from a single tuber. Future Outlook: Future research could focus on further optimizing ultrasound application techniques in potato cultivation, considering diverse varieties and environmental conditions. Additionally, it would be worthwhile to analyze the long-term effects of ultrasound on tuber seed potato quality and their ability to adapt to changing climatic and soil conditions. Furthermore, studies investi-gating the impact of ultrasound on other plant species could broaden our understanding of po-tential benefits in agriculture.

Amid the swift progression of the global automobile industry, the aspiration for lightweight vehicle design has surfaced as a crucial approach to boost fuel efficiency and curtail environmental impact. The objective of this study revolves around achieving holistic optimization of vehicle structure via detailed scrutiny of vehicle process characteristics, amalgamated with a Back Propagation neural network (BPNN) optimized by a genetic algorithm (GA) and a topology optimization (TO) method.The process initiates with an examination of the vehicle's technical characteristics, succeeded by an optimization protocol that couples GA with BPNN. This exhaustive optimization procedure derives the best-fit values of design parameters and identifies the globally optimal lightweight design approach. Subsequently, a comprehensive structural optimization is actualized by modifying the topological distribution of the structure.A simulation experiment of the conceptual car body beam skeleton is conducted as a conclusive step, and the anti-collision capacity of the car body beam skeleton is assessed by measuring deformation intrusion. The findings reveal that in the vehicle topology optimization, a comparative analysis of pre and post-optimization results indicates an improved topological density across diverse sections. The topological density of the vehicle's frontal structure escalates from 0.75 to 0.8. Following optimization, the stiffness assessment records a marginal increase (within the range of 0.02–0.05), implying that the lightweight design does not compromise the general rigidity of the structure.The optimized body structure manifests superior crashworthiness in the crash test: the deformation intrusion diminishes by 27% in front-end collisions. In side impacts, the deformation and intrusion at critical points are reduced by 13.15% to 10% respectively. The comprehensive method proposed herein proves to be an efficient strategy to actualize the lightweight design of vehicles.

With the continuous update of gene editing technology, great progress has been made in livestock breeding, researchers have produced gene edited pigs, cattle, sheep and other improved livestock. Gene editing technology is a genetic means to knock in, knock out, delete, inhibit, activate or replace specific bases of DNA or RNA sequences at the genome level to achieve accurate modification, and can edit genes at a fixed point without the need for DNA templates. In recent years, although regular clusters of interspaced short palindromic repeats (CRISPR)/Cas9 system mediated gene editing technology has been widely used in animal genetic breeding research, but so far, the system's precise insertion efficiency of foreign genes is not high enough, and there are certain off-target effects, and it is not enough to be used in genome editing of large livestock such as cashmere goats. In this paper, the development status, challenges, application prospects and look into the distance of CRISPR/ Cas9-mediated precisiongene editing technology in livestock breeding were reviewed, in order to provide theoretical reference for livestock gene function analysis, genetic improvement and livestock breeding with local economic characteristics.

In this study, a design of Morlet wavelet neural networks (MWNNs) is presented to solve the prediction differential model (PDM) using the global approximation capability of genetic algorithm (GA) and local quick interior-point algorithm scheme (IPAS), i.e., MWNN-GAIPAS. The famous PDM is known as a variant of functional differential system that works as an opposite of the historical delay differential models. A fitness function is optimized using the mean square error by applying the GA-IPAS for solving the PDM. Three PDM examples have been presented numerically to check the authenticity of the MWNN-GAIPAS. For the perfection of the designed MWNN-GAIPAS, the comparability of the obtained results and exact results is performed. Moreover, the neuron analysis is performed by taking the 3, 10 and 20 number of neurons. The statistical observations have been performed to authenticate the reliability of the MWNN-GAIPAS for solving the PDM.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, Xanthogranuloma Juvenile, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nefroblastoma in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play crucial roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are crucial for improving outcomes in these individuals.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and few disease-targeted therapies exist. To identify, focal, spatially restricted alterations in transcriptional pathways and reveal novel therapeutic targets, we performed a spatial transcriptomic analysis of areas of focal myocyte disarray compared to areas of normal tissue, using a commercially available platform (GeoMx, nanoString). We analyzed surgical myectomy tissue from four patients with HCM and control interventricular septum tissue from two unused organ donor hearts that were free of cardiovascular disease. Histological sections were reviewed by an expert pathologist and 72 focal areas with varying degrees of myocyte disarray (normal, mild, moderate, severe) were chosen for analysis. Areas of interest were interrogated with the Human Cancer Transcriptome Atlas designed to profile 1800 transcripts. Differential expression analysis revealed significant changes in gene expression between HCM and Control tissue, and functional enrichment analysis indicated these genes were primarily involved in interferon production and mitochondrial energetics. Within HCM tissue, differentially expressed genes between areas of mild and moderate disarray were enriched for genes related to mitochondrial energetics (moderate disarray) and response to oxygen/cytokine levels (mild disarray). The comparison between areas of moderate and severe disarray were enriched for genes related to the c-Jun N-terminal kinase (JNK) cascade in severe disarray. Analysis of ligand-receptor pair gene expression revealed that HCM tissue exhibited downregulation of platelet-derived growth factor (PDGF), NOTCH, junctional adhesion molecule, and CD46 signaling, while showing upregulation of fibronectin, CD99, cadherin, and amyloid precursor protein signaling. A deconvolution analysis utilizing the matched single nuclei RNA-sequencing (snRNA-seq) data to determine cell type composition in areas of interest revealed significant differences in fibroblast and vascular cell composition in areas of severe disarray when compared to normal areas in HCM samples. Cell composition in normal areas from control tissue was also divergent from normal areas in HCM samples, which was consistent with the differential expression results. Overall, our data identify novel and potential disease-modifying targets for therapy in HCM.