Missing observation is a common problem in scientific and industrial experiments, particularly in a small-scale experiment. They often present significant challenges when experiment repetition is infeasible. In this research, we propose a multi-objective genetic algorithm as a practical alternative for generating optimal mixture designs that remain robust in the face of missing observation. Our algorithm prioritizes designs that exhibit superior D-efficiency while maintaining a high minimum D-efficiency due to missing observation. The focus on D-efficiency stems from its ability to minimize the impact of missing observations on parameter estimates, ensure reliability across the experimental space, and maximize the utility of available data. We study problems with three mixture components where the experimental region is an irregularly shaped polyhedral within the simplex. Our designs have proven to be D-optimal designs, demonstrating exceptional performance in terms of D-efficiency and robustness against missing observations. We provide a well-distributed set of optimal designs derived from the Pareto front, enabling experimenters to select the most suitable design based on their priorities using the desirability function.

The genetic diversity of local coffee populations is crucial to breed new varieties better adapted to the increasingly stressful environment due to climate change and the evolving consumer preferences. Unfortunately, local coffee germplasm conservation and genetic assessment have not received much attention. Molecular tools offer substantial benefits in identifying and selecting new cultivars or clones suitable for sustainable commercial utilization. New annotation methods, such as chloroplast barcoding, are necessary to produce accurate and high-quality phylogenetic analyses. This study used DNA barcoding techniques to examine the genetic relationships among fifty-six accessions collected from the southern part of Saudi Arabia. PCR amplification and sequence characterization were used to investigate the effectiveness of four barcoding loci, namely atpB-rbcl, TrnL-TrnF, TrnT-TrnL, and TrnL. The maximum nucleotide sites, nucleotide diversity, and an average number of nucleotide differences were recorded for atpB-rbcl, while TrnT-TrnL had the highest variable polymorphic sites, segregating sites, and haploid diversity. Among the four barcode loci, TrnT-TrnL recorded the highest singleton variable sites, while TrnL recorded the highest parsimony information sites. Furthermore, the phylogenetic analysis clustered the Coffea arabica genotypes into four different groups, with three genotypes (KSA31, KSA38, and KSA46) found to be the most divergent genotypes standing alone in the cluster and remained apart during the analysis. The study demonstrates the presence of considerable diversity among coffee populations in Saudi Arabia. Furthermore, it also shows that DNA barcoding is an effective technique for identifying local coffee genotypes, with potential applications in coffee conservation and breeding efforts.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

Fluctuating stock prices make it difficult for investors to see investment opportunities. One tool that can help investors overcome this is forecasting techniques. Long Short-Term Memory (LSTM) is one of deep learning methods used in forecasting time series. The training and success of deep learning is strongly influenced by the selection of hyperparameters. This research uses a hybrid method between the Genetic Algorithm (GA) and LSTM to find a suitable model for predicting stock prices. GA is used in optimizing the architecture such as the number of epochs, window size, and the number of LSTM units in the hidden layer. Tuning optimizer is also carried out using several optimizers to achieve the best value. From method that has been applied, it shows that the method has a good level of accuracy with MAPE values below 10% in every optimizer used. The error rate generated is quite low, in case-1 with a minimum RMSE value of 93.03 and 94.40, & in case-2 with an RMSE value of 104.99 and 150.06 during training and testing. A fairly stable and small value is generated by setting it using the Adam Optimizer.

Mannheimia haemolytica is the main pathogen contributing to pneumonic pasteurellosis in sheep. The aim of this study was to investigate the antimicrobial resistance levels in M. haemolytica from the lungs of slaughtered sheep and the genetic resistance mechanisms involved. A total of 256 M. haemolytica isolates, 169 from lungs with pneumonic lesions and 87 without, were analyzed by the disk diffusion method for 12 antimicrobials, and the whole genome of 14 isolates sequenced to identify resistance determinants. Levels of phenotypic resistance ranged from <2 % for 10 antimicrobials (amoxicillin, amoxicillin-clavulanic, ceftiofur, cefquinome, lincomycin/spectinomycin, gentamicin, erythromycin, florfenicol, enrofloxacin, and doxycycline) to 4.3% for tetracycline and 89.1% for tylosin. Six isolates carried tetH genes and four carried, in addition, strA and sul2 genes in putative plasmid sequences. No mutations associated with macrolide resistance were identified in 23 rDNA sequences suggesting that M. haemolytica phenotypic results for tylosin should be interpreted with care in the absence of well-established epidemiological and clinical breakpoints. The identification of strains phenotypically resistant to tetracycline and of several resistance genes, some of which were present in plasmids, highlight the need for continuous monitoring of susceptibility patterns in Pasteurellaceae isolates from livestock

Alum sludge is a byproduct of water treatment plants and its use as a soil stabilizer has gained increasing attention due to its economic and environmental benefits. Its application has been shown to improve the strength and stability of soil, making it suitable for various engineering applications. However, to go beyond just measuring the effects of alum sludge as a soil stabilizer, this paper explores the use of artificial intelligence (AI) methods to predict the California bearing ratio (CBR) of soils stabilized with alum sludge. Three AI methods, including two black box methods (artificial neural network and support vector machines) and one grey box method (genetic programming), were used to predict CBR based on a database with nine input parameters. The results showed that all three AI models were able to predict CBR with good accuracy, with coefficient of determination (R2) values ranging from 0.94 to 0.99 and mean absolute error (MAE) values ranging from 0.30 to 0.51. In a novel approach, the genetic programming method was used to produce an equation to estimate CBR, which included seven inputs and accurately predicted CBR. The analysis of sensitivity and importance of parameters showed that the number of hammer blows for compaction was the most important parameter, while the parameters for maximum dry density of soil and mixture were the least important. This study suggests that AI methods can effectively predict the performance of alum sludge as a soil stabilizer, and the proposed equation using genetic programming can be a useful tool for predicting CBR.

Here we investigated the longer-term effect of Ncald-ASOs by additional i.c.v. bolus injection at PND28. Two weeks after injection of 500 µg Ncald-ASO in wild-type mice, NCALD was significantly reduced in brain and spinal cord and well tolerated. Next, we performed a double-blinded preclinical study combining low-dose SMN-ASO (PND1) with 2x i.c.v. Ncald-ASO or CTRL-ASO (100 µg at PND2, 500 µg at PND28). Ncald-ASO re-injection significantly ameliorated electrophysiological defects and NMJ denervation at 2 months. Moreover, we developed and identified a nontoxic and highly efficient human NCALD-ASO that significantly reduced NCALD in hiPSCs-derived MNs. This improved both neuronal activity and growth cone maturation of SMA MNs, emphasizing the additional protective effect of NCALD-ASO treatment.

Among the various complex systems that we experience each day, there is the physical phenomenon of infiltration. Infiltration is considered as the dynamics of water flow in the subsurface soil that in this work is framed for the context of civil construction. This issue is approached with the use of mathematical models and stochastic techniques, however, there are hardships in collecting the samples in the field, the adoption of a scale type, the influence in soil layers interfaces, the effects of soil anisotropic characteristics and so on. In this study, methodology is proposed to deal with the soil sampling input such as the retro model, constitutive model and optimization algorithms. Additionally, an automatic calibration is set forth to fix parameters from the mathematical model submitted. Especially among the existing Optimization Algorithms there are Genetic Algorithms and the Generalized Simulated Annealing Algorithm (GSA). This work presents an overview of these optimization methods and a proposal for a more efficient and faster algorithm called GSA-HYBRID based on convergence gradient technique. The applied strategy depends on the type of case study considering its physical properties and constraints. In this sense, it is found that while Genetic Algorithms are able to replicate the optimization surface, Generalized Simulated Annealing is much more adequate in characterizing the system at an extremely low computational cost. Nevertheless, the hybrid technique GSA-HYBRID performed the fastest. Further research is necessary to implement the novel GSA-HYBRID algorithm due to its flexibility and higher speed, also, studying its application at different case studies.

Shewanella spp. are gram-negative bacteria that thrive in aquatic niches and also cause infectious diseases as opportunistic pathogens. Chromosomal integrons (CI) and mobile integrons (MI) were previously described in some Shewanella isolates. Here, we evaluated the occurrence of integrase genes, the integron systems and their genetic surroundings in the genus. We identified 22 integrase gene types, 17 of which were newly described, in different Shewanella species, evidencing multiple gain and loss events. Phylogenetic analysis showed that most of them were strain-specific, except for Shewanella algae, which seem to have co-evolve within the host as typical CIs. Noteworthy, co-existence of up to 5 different integrase genes, as well as their wide dissemination to Alteromonadales, Vibronales, Chromatiales, Oceanospirillales and Enterobacterales was observed. Identification of novel MIs suggests that lateral genetic transfer may have occurred resembling the behavior of class 1 integrons. The constant emergence of determinants associated to antimicrobial resistance worldwide, concomitantly with novel MIs in strains capable to harbor several types of integrons may be an alarming threat for the recruitment of novel antimicrobial resistance gene cassettes in the genus Shewanella, and its evolution towards the multidrug resistance.

Computer network attacks are evolving in parallel with the evolution of hardware and neural network architecture. Despite major advancements in Network Intrusion Detection System (NIDS) technology, most implementations still depend on signature-based intrusion detection systems, which can’t identify unknown attacks. Deep learning can help NIDS to detect novel threats since it has a strong generalization ability. The deep neural network’s architecture has a significant impact on the model’s results. We propose a genetic algorithm based model to find the optimal number of hidden layers and the number of neurons in each layer of the deep neural network (DNN) architecture for the network intrusion detection binary classification problem. Experimental results demonstrate that the proposed DNN architecture shows better performance than classical machine learning algorithms at a lower computational cost.

: Using line × tester analysis, the current research analyses parental genotypes and their combinations in normal conditions and identifies the genes influencing yield characteristics. In the present study, 15 diverse genotypes, including 10 lines, 5 testers, and 50 F1s hybrids, were evaluated for 13 morphological and 2 biochemical traits. A suitable location was taken to study the effect of 15 characters. The results exposed that ability mean squares were significant for all studied additive and non-additive components. In this direction, the general combining ability of PBW-343, DBW-39, K-402, K-1317, KRL-210, and K-68 were higher than the remaining parents. For morphological traits like yield, the top five crosses were described based on SCA effects, namely, HD-3086 × HD-3171, K-402 × K-9107, K-1317 × K-9107, HD-2967 × K-0307 and K-402 × K-68 in F1 generation. In addition, the high value of heritability was estimated for plant height (77.32%), spike length (32.26%), biological yield/plant (59.52%), and grain yield/plant (68.76%). However, the moderate values of heritability were estimated for days to maturity (22.78%) and phenol color reaction (18.00%). The higher genetic advance was not found for recorded characters; however, a moderate genetic advance was recorded for grain yield per plant (13.15%) and harvest index (11.72%). High heritability coupled with moderate genetic advance was recorded for two characters grain yield per plant and harvest index in F1 and F2 generations.

Since its advent in the mid-twentieth century, the field of artificial intelligence (AI) has been heavily influenced by biology. From the structure of the brain to evolution by natural selection, core biological concepts underpin many of the fundamental breakthroughs in modern AI. Here, focusing specifically on artificial neural networks (ANNs) that have become commonplace in machine learning, we show the numerous connections between theories based on coevolution, multi-level selection, modularity and competition and related developments in ANNs. Our aim is to illuminate the valuable but often overlooked inspiration biologists have provided AI research and to spark future contributions at this intersection of biology and computer science. Although recent advances in AI have been swift, many significant challenges remain requiring innovative solutions. Thankfully, biology in all its forms still has a lot to teach us, especially when trying to create truly intelligent machines.

Clustered regularly interspaced short palindromic repeats or CRISPR, one of the major technological tools from nature's toolbox, has revolutionized the scientific world with its potential use in humans and plants. CRISPR Cas9 was first known as an adaptive immune system of bacteria. It is a system that cleaves foreign DNA. It has been exploited to be used as a genome editing tool for correcting genetic diseases in humans, for plants to create stress-resistant plants, and for a variety of different purposes. This review provides a basic overview of its applications in different areas of biological research. It has immense potential for a variety of researches, but it's still a mystery for science. It feels like scientists just know a tip of an iceberg.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the one of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

CRISPR-Cas9 technology allows the modification of DNA sequences in vivo at the location of interest. Although CRISPR-Cas9 can produce genomic changes that do not require DNA vector carriers, the use of transgenesis for stable integration of DNA coding for gene-editing tools into plant genomes is still the most used approach and it can generate unintended transgenic integrations, while Cas9 prolonged expression can increase cleavage at off-target sites. In addition, the selection of genetically modified cells from millions of treated cells, especially plant cells, is still challenging. These downfalls can be avoided with the delivery of preassembled ribonucleoprotein complexes (RNPs) composed of purified recombinant enzyme Cas9 and in vitro- transcribed guide RNA (gRNA) molecules in a protoplast system. We therefore aimed to develop the first DNA-free protocol for gene-editing in maize and introduced RNPs into their protoplasts with PEG 4000. We performed effective transformation of maize protoplasts using different gRNAs sequences targeting the inositol phosphate kinase gene and applying two different exposure times to RNPs. Using low-cost Sanger sequencing protocol, we observed an efficiency rate of 0.85 up to 5.85%, which is equivalent to DNA-free protocols used in other plant species. A positive correlation was displayed between exposure time and mutation frequency. Mutation frequency was gRNA sequence- and exposure time-dependent. In summary, we demonstrated the suitability of RNP transfection as an effective screening platform for gene-editing in maize. This efficient and relatively easy assay method for selection of gRNA suitable for editing of gene of interest will be highly useful for genome editing in maize, since genome size and GC-content are large and high in maize genome, respectively. Nevertheless, the large amplitude of mutations at target site requires scrutiny when checking mutations at off-target sites and potential safety concerns.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the most important of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. Through ubiquitination, this heterodimer has significant effects on individual proteins, enabling, among others, the destruction of damaged DNA fragments. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

Photogrammetry involves aerial photography of the earth’s surface and subsequently processing the images to provide a more accurate depiction of the area (Orthophotography). It’s used by the Spanish Instituto Geográfico Nacional to update road cartography but requires a significant amount of manual labor due to the need to perform visual inspection of all tiled images. Deep Learning techniques (artificial neural networks with more than one hidden layer) can perform road detection but it is still unclear how to find the optimal network architecture. Our system applies grammar guided genetic programming to the search of deep neural network architectures. In this kind of evolutive algorithm all the population individuals (here candidate network architectures) are constrained to rules specified by a grammar that defines valid and useful structural patterns to guide the search process. Grammar used includes well-known complex structures (e.g. Inception-like modules) combined with a custom designed mutation operator (dynamically links the mutation probability to structural diversity). Pilot results show that the system is able to design models for road detection that obtain test accuracies similar to that reached by state of the art models when evaluated over a dataset from the Spanish National Aerial Orthophotography Plan.

Bitter gourd is an important vegetable of the family Cucurbitaceae, cultivated mainly in humid and subtropical Asia. Bitter gourd is vegetable with immense health benefits due to the presence of medicinal compounds such as charatin, vicine, and polypeptide-p, which play an essential role in lessening the blood glucose levels. Moreover, bitter gourd fruits are particularly rich in vitamin C, minerals, and carotenes. Here, an effort has been made to critically evaluate the extent of achievements during the enhancement and enactment of bitter gourd breeding programs with the use of latest technologies. Broadening of the genetic base of cultivated bitter groud varieties as a result of enrichment of the existing resources by using the wild species in the breeding programs. Practical seed production technological know-how along with the use of the MS system (male sterility)/chemical-induced sterility procedure is nonetheless vital to cope up with the market demands. Superior yielding bitter gourd hybrids combining early maturity and resistance to biotic and abiotic stresses are regularly needed to cope up with the challenge of bitter gourd production.

Artemia franciscana, native to America, has recently colonized non-indigenous populations in Eurasia, Mediterranean regions and Australia. In present we sought to evaluate the potential effects of colonization of A. franciscana on genetic differentiation in the new environments in UAE. We used the COI marker to determine population genetic structure and identify the origins of exotic populations in UAE. Our findings have confirmed the colonization of both localities by A. franciscana. Genetic variation of invasive A. franciscana were exclusively lower than native population in Great Salt Lake and San Francisco Bay. Results have showed the studied population could not possibly have colonized directly from natural American localities, perhaps resulting from secondary introduction events from other non-indigenous populations. Genetic analysis have yielded different demographic patterns for invasive studied populations. Al Wathba Wetland Reserve (AWWR) population have represented demographic expansion. In contrast, Godolphin Lakes (GL) population was at demographic equilibrium. Neutrality tests have documented the excess of both recent and historical mutations in the COI gene pool of invasive AWWR Artemia throughout establishment in the new environment.

In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.

The ASCE-EWRI reference evapotranspiration (ETo) equation is recommended as a standardized method for reference crop ETo estimation. However, various climate data as input variables to the standardized ETo method are considered limiting factors in most cases and restrict the ETo estimation. This paper assessed the potential of different machine learning (ML) models for ETo estimation using limited meteorological data. The ML models used to estimate daily ETo included Gene Expression Programming (GEP), Support Vector Machine (SVM), Multiple Linear Regression (LR), and Random Forest (RF). Three input combinations of daily maximum and minimum temperature (Tmax and Tmin), wind speed (W) with Tmax and Tmin, and solar radiation (Rs) with Tmax and Tmin were considered using meteorological data during 2003–2016 from six weather stations in the Red River Valley. To understand the performance of the applied models with the various combinations, station, and yearly based tests were assessed with local and spatial approaches. Considering the local and spatial approaches analysis, the LR and RF models illustrated the lowest rate of improvement compared to GEP and SVM. The spatial RF and SVM approaches showed the lowest and highest values of the scatter index as 0.333 and 0.457, respectively. As a result, the radiation-based combination and the RF model showed the best performance with higher accuracy for all stations either locally or spatially, and the spatial SVM and GEP illustrated the lowest performance among models and approaches.

Oats represents a promising alternative to small-grain cereals from Triticeae group (wheat, barley, rye) for persons suffering from any form of gluten intolerance, especially celiac disease (CD), since oat-specific prolamins avenins reveal generally lower gluten content and immunoreactivity. Recent studies on avenin molecular structure revealed large genetic variability in avenin sequences affecting the spectrum of gluten peptides produced by hydrolases in human digestive tract. The aim of the present review is to summarise recent knowledge obtained in laboratory in vitro studies focused on the effect of avenin-derived peptides on reactivity of crucial components of human immune system such as dendritic cells (DC) and T-cells. The other part of the review summarises the results of clinical studies with CD patients including oat products in their diet. Since different clinical studies revealed contradictory results regarding potential safety of oats for CD patients, the focus has to be directed at genetic variability in oat avenins. Identification of avenin isoforms with minimum CD immunoreactivity will open up ways leading to designing novel oat cultivars suitable for CD patients. Knowledge on immunoreactivity of gluten peptides together with breeding new oat cultivars revealing minimum avenin immunoreactivity with respect to CD as well as application of food processing technologies leading to gluten content reduction should result in development of gluten-free oats safe for celiacs.

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

In the past, Unmanned Aerial Vehicles (UAVs) were mostly used in the military operations to prevent pilot losses. Nowadays, the fast technological evolution enables the production of a class of cost-effective UAVs which can service a plethora of public and civilian applications, specially when configured to work cooperatively to accomplish a task. However, designing a communication network among the UAVs is challenging task. In this article, we propose a centralized UAV placement strategy, where UAVs are used as flying access points forming a mesh network, providing connectivity to ground nodes deployed in a target area. The geographical placement of UAVs is optimized based on a Multi-Objective Evolutionary Algorithm (MOEA). The goal of the proposed scheme is to cover all ground nodes using a minimum number of UAVs, while maximizing the fulfillment of their data rate requirements. The UAVs can employ different data rates depending on the channel conditions, which are expressed by the Signal-to-Noise-Ratio (SNR). In this work, elitist Non-Dominated Sorting Genetic Algorithm II (NSGA-II) is used to find a set of optimal positions to place UAVs, given the positions of the ground nodes. We evaluate the trade-off between the number of UAVs used to cover the target area and the data rate requirement of the ground nodes. Simulation results show that the proposed algorithm can optimize the UAV placement given the requirement and the positions of the ground nodes in the geographical area.

This mini-review provides an overview of traditional, emerging, and future applications of lactic acid bacteria (LAB) and discusses how genome editing tools can be used to overcome current challenges in all these applications. It also describes currently available tools and how these can be further developed, and takes current legislation into account. Genome editing tools are necessary for the construction of strains for new applications and products, but can also play a crucial role in traditional ones, such as food and probiotics, as a research tool for understanding mechanistic insights and discovering new properties. Traditionally, recombinant DNA techniques for LAB have strongly focused on being food-grade, but they lack throughput and the number of genetically tractable strains is still rather limited. Further tool development in this direction will enable rapid construction of multiple mutants or mutant libraries on a genomic level in a wide variety of LAB strains. We also propose an iterative Design-Build-Test-Learn workflow cycle for LAB cell factory development based on systems biology, with “cell factory” expanding beyond its traditional meaning of production strains and making use of high-throughput genome editing tools to advance LAB understanding, applications and strain development.

This paper presents an alternative constraint handling approach within a specialized genetic algorithm (SGA) for the optimal reactive power dispatch (ORPD) problem. The ORPD is formulated as a nonlinear single-objective optimization problem aiming to minimize power losses while keeping network constraints. The proposed constraint handling approach is based on a product of sub-functions that represents permissible limits on system variables and that includes a specific goal on power loss reduction. The main advantage of this approach is the fact that it allows a straightforward verification of both feasibility and optimality. The SGA is examined and tested with the proposed constraint handling approach and the traditional penalization of deviations from feasible solutions. Several tests are run in the IEEE 30, 57, 118 and 300 bus test power systems. The results obtained with the proposed approach are compared to those offered by other metaheuristic techniques reported in the specialized literature. Simulation results indicate that the proposed genetic algorithm with the alternative constraint handling approach yields superior solutions when compared to other recently reported techniques.

Nowadays, we live in a world in which people are facing with a lot of data that should be stored or displayed. One of the key methods to control and manage this data refers to grouping and classifying them in clusters. Today, clustering has a critical role in information retrieval methods for organizing large collections inside a few significant clusters. One of the main motivations for the use of clustering is to determine and reveal the hidden and inherent structure of a set of data. Ensemble clustering algorithms combine multiple clustering algorithms to finally reach an overall clustering system. Ensemble clustering methods by lack of information fusing utilize several primary partitions of data to find better ways. Since various clustering algorithms look at the different data points, they can produce various partitions from such data. It is possible to create a partition with high performance by combining the partitions obtained from different algorithms, even if the clusters to be very dense from each other. Most studies in this area have examined all the initial clusters. In this study, a new method is used in which the most sustainable clusters are utilized instead of all primary produced clusters. Consensus function based on co-association matrixes used to select more stable clusters. The most stable clusters selection method is done by cluster stability criterion based on F-measure. Optimization functions are used to optimize the obtained final clusters. The genetic algorithm is the optimizer used in this article to find the ultimate clusters participated in a consensus. Experimental results on several datasets show that the output of proposed method is various clusters with high stability.

On-going intensification of rice production systems in Southeast Asia is causing devastating yield losses each year due to rice hoppers. Continuing development of immunity to resistant rice varieties and pesticide application further complicate this problem. Hence, there is a high demand for biological control agents. Egg parasitoid wasps are among the most important natural enemies of rice hoppers such as Nilaparvata lugens and Nephotettix spp. However, our knowledge on their diversity is still very limited due to their small size and the lack of available morphological information. Classifying these parasitoids is the first step to properly understand their role in the rice agroecosystem. We used traditional morphological identification as well as DNA sequencing of COI and 28S genes to investigate the diversity of four important hopper egg parasitoid genera in the Philippines. Parasitoids of the genera Anagrus spp., Oligosita spp., Gonatocerus spp. and Paracentrobia spp. were collected in eight study landscapes located in Luzon. We found discrepancies between the morphological and the molecular analysis. Morphological and molecular results were only valid for Paracentrobia spp. Anagrus spp. and Gonatocerus spp. showed more genetic diversity, than expected after the morphological analysis, indicating cryptic species. The sequences for Oligosita spp. revealed less variation than expected. This is the first study on molecular diversity of rice parasitoids in the Philippines. More research combining morphological, behavioural and genetic methods as well as the establishment of a comprehensive DNA database is urgently needed to assess the performance and suitability of these organisms as biocontrol agents.

Coxsackievirus A6 (CVA6) has become increasingly clinically relevant as a cause of Hand, Foot and Mouth Disease (HFMD) globally since 2008. However, most laboratories do not routinely determine the enteroviral type of positive samples. The non-pharmaceutical measures introduced to curb transmission during the SARS-CoV-2 pandemic may also have been perturbed CVA6 epidemiology. We thus aimed to determine the prevalence, clinical presentation and genetic relationship of CVA6 across three complete epidemic seasons: one pre- and two post-SARS-CoV-2-emergence in our regional healthcare setting. Surplus diagnostic nucleic acid from diagnosed enteroviral positives diagnosed between September to December 2018 and May 2021 to April 2023 was subject to VP1 gene sequencing to determine CVA6 cases and interrogate their phylogenetic relationship. Confirmed CVA6 cases were also retrospectively clinically audited. CVA6 infections were identified in 33 and 69 individuals pre- and post-pandemic respectively, with cases peaking in November of 2018 and 2022, but in October of 2021. HFMD was the primary diagnosis in 85.5% of post-pandemic cases, but only 69.7% pre-pandemic, where respiratory and neurological symptoms (45.5% and 12.1% respectively) were significantly elevated. Complete VP1 sequence was retrieved for 94% of CVA6 cases, revealing study infections were genetically diverse and suggestive of multiple local and international transmission chains. CVA6 presented a significant clinical burden in our regional UK hospital setting both pre- and post-pandemic and was subject to dynamic clinical and genetic epidemiology.

Stem cell-derived therapies have shown substantial promise in regenerative medicine for the treatment of degenerative diseases and injuries. Mesenchymal Stem Cells (MSCs) exhibit a remarkable capacity to differentiate into diverse cell types, modulate immune responses, and facilitate tissue repair. Nevertheless, concerns regarding their potential to induce tumors arise from their intrinsic properties, environmental factors, and genetic mutations that occur during handling. This review explores the intricate challenges associated with the tumorigenic potential of stem cell-derived therapeutic products and examines the underlying mechanisms contributing to this risk, such as oncogene activation, suppression of tumor suppressor genes, and the influence of the microenvironment on stem cell behavior. Furthermore, it delves into the role of epigenetic modifications and chromosomal aberrations in cell culture and expansion. This article provides an overview of strategies to mitigate tumorigenic risks, encompassing rigorous quality control measures, refined differentiation protocols, and advanced screening techniques. It also highlights innovative approaches, such as gene editing technologies and small-molecule modulation of stem cell behavior, as promising avenues to enhance safety. Despite these challenges, ongoing research and technological advancements are actively addressing these concerns to ensure safer and more effective utilization of stem cell-based therapies in clinical settings.

Apple-tree (Malus × domestica Borkh.) belongs to the genus Rosaceae. Due to its adaptability and tolerance to different soil and climatic conditions, it is cultivated worldwide for fresh consump-tion. Therefore, the priorities of apple growers are the high-quality of fruits and stable yield for high production. In total about 90 to 95 percent of fruits should fall or be eliminated from apple trees to avoid overcropping and poor-quality fruits. Several technologies such as handwork, me-chanically or chemical substances are used for fruit and bud elimination. The most profitable in commercial orchards is the use of chemicals for elimination, but due to the European Green Deal more environmentally sustainable solutions are required. Elimination of fruitlets is influenced by several factors. Additionally, the apple trees have the self-elimination mechanism. This is de-termined by apple genotype, physiological futures and genetics. This review focuses on the bio-logical factors and genetics mechanisms in apple yield self-regulation for better understanding the regulatory mechanism of fruitlets abscission for future breeding programs targeted on self-regulating yield apple varieties

Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution, and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.

This study explored the intricate nexus between public service provision and land use planning, with a specific focus on the conservation of local plant species in Tambon Khao Phanom, Amphoe Khao Phanom, Krabi Province. Rooted in commitment. The research framework encompasses three fundamental activities: resource survey and collection, resource conservation and utilization, and resource development planning for public services, emphasizing land use planning for local plant species conservation. This multidisciplinary approach integrates the one-map method and draws data from the Department of Land Development to formulate a comprehensive land utilization plan that optimizes land use for biodiversity conservation. This study underscores the critical synergy between public service delivery and land use planning, highlighting their collective potential to advance community well-being and sustainable development.

Infantile Neuroaxonal Dystrophy (INAD) is a rare neurodegenerative disorder, affecting 1:1,000,000 population. It results from pathogenic variants in the PLA2G6 gene located on chromosome (22q13.1). The onset of symptoms usually occurs between 6 to 18 months, causing developmental regression leading to debilitating symptoms such as muscle weakness, dementia, and loss of basic skills. Eventually, it progresses to life-threatening symptoms including breathing difficulties, which limits the life expectancy to 5-10 years. While potential genetic therapy for treatment is are being developed, they are yet to be approved for use, and management remains essentially supportive. This case report is of a 9-year-old Pakistani girl with INAD. She presented with recurrent chest infections, developmental regression, loss of speech, paralysis, hypertension, and eventually breathing difficulties. Brain magnetic resonance imaging and genetic testing con-firmed the diagnosis. This case posed diagnostic challenges in view of its overlapping clinical presentation. Through this report, we aim to raise awareness about the condition among practitioners, outline the importance of genetic counseling in susceptible couples and suggest potential areas of further research.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

One of the main factors that influence the fertility of cattle in grazing systems in hot tropical climates is heat stress. The objective of this study was to evaluate the effect of season, breed, hormonal and physiological condition on the quantity and quality of cumulus-oocyte complexes (COCs) and embryos produced in vitro, from Romosinuano (RM) and Tropical Milking (TM) donors. Three ovum pick-up and in vitro fertilization (OPU-IVF) were performed, one per season; hot dry (HD; 10, 10), hot humid (HH; 9, 9) and fresh dry (FD; 7, 10) in RM and LT donors. Serum levels of cortisol, insulin and glucose were measured, in addition to heart rate (HR), respiratory rate (RR) and rectal temperature (RT). Effect of season x genotype interaction (p≤0.05) was observed in all COCs variables and only in cleavage embryos (CLI) (p≤0.05). Body weight (BW) affected all COCs variables (p≤0.01), except unviable (UNV) although affected degenerated embryos (DEG) (p≤0.01) and total blastocysts (BLAST) (p≤0.01). Cow age only affected viable COCs (VIAB) (p ≤ 0.05), code one blastocysts (BC1) and BLAST (p≤0.01). Cortisol affected total COCs (COCsT), VIAB and total matured in vitro (TMIV) (p≤0.01), as well as CLI, BC1 (p≤0.01) and BLAST (p≤0.05). Insulin affected COCsT (p≤0.01), UNV (p≤0.05), denuded oocytes (DE) (p≤0.01), BC1 and code two blastocysts (BC2) (p≤0.01). Glucose affected all COCs variables (p≤0.01), except UNV and all embryo variables except BC2. HR affected COCsT, DE, TMIV (p≤0.01), CLI, BLAST and DEG (p≤0.05). RR affected COCsT, UNV, VIAB, CLI (p≤0.05), BC1, BLAST and DEG (p≤0.01). RT only affected DE, VIAB (p≤0.01) and BLAST (p≤0.05). The seasonal climatic year variation of Veracruz and changes in physiological and hormonal variables have diverse effects on the cumulus-oocyte complexes and embryos produced by RM and TM donors.

Juvenile Polyposis Syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knockout on the development of intestinal polyps using Collaborative Cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knockout mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knockout males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knockout, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-Nearest Neighbours and Linear Regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides a comprehensive understanding of the intricate genetic interplay in the context of Smad4 knockout, offering valuable insights into potential therapeutic targets for juvenile polyposis and related diseases.

Ajuga arabica is an essential medicinal plant found naturally in Saudi Arabia, recognized for its therapeutic characteristics. Nevertheless, research on the genetic diversity and population arrangement of this species in Saudi Arabia is deficient. In this study, we conducted a comparative examination of DNA and gene sequences to evaluate the genetic diversity and population configuration of Ajuga arabica in Saudi Arabia. Our findings demonstrate that there are high levels of genetic diversity within populations, but low levels of genetic differentiation among populations. Moreover, we discovered proof of gene flow among populations, suggesting that there are no significant genetic barriers to gene flow. Our results offer valuable insights into the genetic diversity and population structure of Ajuga arabica in Saudi Arabia, which can support conservation efforts and promote the sustainable use of this valuable medicinal plant.

Advancements in genomics and molecular biology have propelled our understanding of genetic information far beyond the iconic double helix structure of DNA. This comprehensive review delves into the intricate world of DNA and RNA networks, exploring the complexities that extend beyond the classical model. We investigate the dynamic interactions, regulatory mechanisms, and functional implications of the broader genetic landscape, encompassing both coding and non-coding elements. From chromatin architecture to the diverse array of non-coding RNAs, this exploration seeks to provide a holistic perspective on the multifaceted roles played by DNA and RNA in cellular processes. The three-dimensional organization of genetic material within the cell has emerged as a crucial determinant of cellular function. Chromatin architecture, comprising DNA, histones, and other associated proteins, plays a dynamic role in regulating gene expression. We delve into the intricate choreography of chromatin remodeling, deciphering the interplay between transcription factors, epigenetic modifications, and higher-order structures that modulate gene activity. The exploration of chromatin dynamics unveils a nuanced understanding of how the genome responds to environmental cues, cellular signals, and developmental processes. Moreover, the once-dismissed non-coding portion of the genome has emerged as a key regulator of cellular function. Various classes of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in diverse cellular processes, ranging from fine-tuning gene expression to modulating chromatin structure. The review critically examines the functional roles of these non-coding RNAs, shedding light on their involvement in cellular homeostasis, development, and disease. As I traverse this landscape beyond the double helix, our review synthesizes current knowledge on the intricacies of DNA and RNA networks. By exploring the regulatory mechanisms, functional implications, and emerging paradigms, we aim to inspire a deeper appreciation for the molecular choreography that underlies the cellular symphony of life. Furthermore, we discuss the implications of these findings in the context of disease, highlighting potential diagnostic and therapeutic avenues that arise from a comprehensive understanding of DNA and RNA networks. In doing so, this exploration not only broadens our theoretical understanding but also opens new frontiers for translational research in genetics and molecular medicine.

Certain Trichoderma isolates provide biofertilizer, biocontrol, and other plant-beneficial activities while inhabiting the soil or internal plant issues; and their use in agricultural systems could contribute to sustainable food production. It is thought that this colonization of soil and internal plant tissues is fundamental for biocontrol and biofertilizer applications. Our collective analyses of prior surveys, where the tef1 sequence was almost exclusively used to identify Trichoderma species, showed that isolates from the Harzianum Complex Clade, the T. asperellum/T. asperelloides group, T. virens, T. hamatum, and T. atroviride were prevalent in soil and/or as endophytes. Population structure and genetic diversity of these species were investigated, and new lineages with geo-graphic significance within T. atroviride, T. asperellum, T. hamatum, and T. virens populations were found. The nearest relatives of some species were also revealed. Choosing isolates from among more than 500 known Trichoderma species for use in non-targeted evaluation screens for biocontrol or biofertilizer applications is time-consuming and expensive. Preferentially selecting species from T. atroviride, T. asperellum/T. asperelloides, T. hamatum, species from the T. harzianum Complex Clade, T. virens, and possibly nearest relatives, may speed the identification of candidates for commercialization due to the demonstrated ability of these species to successfully inhabit the soil and endorhizosphere. To our knowledge, this is the first report where dominant soil- and en-dophyte-inhabiting Trichoderma species were identified from past survey data and population structure and genetic diversity analyses conducted.

The high prevalence of thyroid nodules and increased availability of neck ultrasound have led to an increased incidence of diagnostic thyroid fine needle aspirations, with approximately 20% yielding indeterminate results. The recent availability of molecular tests has helped guide the clinical management of these cases. This paper aims to review and compare three main commercially available molecular cytology platforms in the U.S. – Afirma GSC, Thyroseq GC, and ThyGeNEXT+ThyraMIR. Sequential improvements of the Afirma GSC and Thyroseq GC tests have led to higher positive and negative predictive values, sensitivity, and specificity. Comparative studies revealed similar diagnostic performance between these tests, with considerations for factors such as cost and processing time. Thyroseq GC provides detailed genomic information and specific management recommendations. ThyGeNEXT+ThyraMIR, though less studied, presents promising results, particularly in miRNA analysis for weak driver mutations. Challenges in interpreting results include variations in reporting and the evolving nature of testing platforms. Questions persist regarding cost-effectiveness and the utility of ultrasound characteristics in selecting candidates for molecular testing. While molecular testing has primarily served diagnostic purposes, advancements in understanding genetic alterations now offer therapeutic implications. FDA-approved options target specific genetic alterations, signaling a promising future for tailored treatments.

The escalating reliance of modern society on information and communication technology has rendered it vulnerable to an array of cyber-attacks, with distributed denial-of-service (DDoS) at-tacks emerging as one of the most prevalent threats. This paper delves into the intricacies of DDoS attacks, which exploit compromised machines numbering in the thousands or more to disrupt data services and online commercial platforms, resulting in significant downtime and financial losses. Recognizing the gravity of this issue, various detection techniques have been explored, yet the quantitative and prior detection of DDoS attacks has seen a decline in recent methods. This research introduces an innovative approach by integrating evolutionary optimization algorithms and machine learning techniques. Specifically, the study proposes XGB-GA Optimization, RF-GA Optimization, and SVM-GA Optimization methods, employing Evolutionary Algorithms Opti-mization with TOPOT-Genetic Programming. Datasets pertaining to DDoS attacks were utilized to train machine learning models based on XGB, RF, and SVM algorithms, and 10-fold cross-validation was employed. The models were further optimized using evolutionary algo-rithms, achieving remarkable accuracy scores: 99.99% with the XGB-GA method, 99.50% with RF-GA, and 99.99% with SVM-GA. Furthermore, the study employed TPOT to identify the optimal algorithm for constructing a machine learning model, with the genetic algorithm pinpointing XGB-GA as the most effective choice. This research significantly advances the field of DDoS attack detection by presenting a robust and accurate methodology, thereby enhancing the cybersecurity landscape and fortifying digital infrastructures against these pervasive threats.

Tomato is one of the most important vegetable crops grown worldwide. Tomato brown rugose fruit virus (ToBRFV), a seed-borne tobamovirus, poses a serious threat to tomato productions due to its ability to break the resistant genes (Tm-1, Tm-2, Tm-22) in tomato. The objective of this work was to identify new resistance source(s) of tomato germplasm against ToBRFV. To achieve this aim, a total of 476 accessions from 12 Solanum species were tested with the ToBRFV US isolate for their resistance and susceptibility. As a result, a total of 44 asymptomatic accessions were identified as resistance/tolerance, including 31 accessions of S. pimpinellifolium, one accession of S. corneliomulleri, four accessions of S. habrochaites, three accessions of S. peruvianum and five accessions of S. subsection lycopersicon hybrid. Further analysis using serological tests identified four highly resistant S. pimpinellifolium lines, PI 390713, PI 390714, PI 390716 and PI 390717. The inheritance of resistance in the selected lines was verified in next generation and confirmed by RT-qPCR. To our knowledge, this is a first report of high resistance to ToBRFV in S. pimpinellifolium. These new genetic resources will expand the genetic pool available for breeders to develop new resistant cultivars of tomato against ToBRFV.

In this work, we propose a Fog-enabled UAV-as-a-Service (FU-Serve) architecture to address the issues of data transmission delay for serving time-critical Internet of Things (IoT) applications. Traditionally, in a UAV-as-a-Service (UaaS) platform, different UAVs host heterogeneous sensors, which sense the physical phenomenon and transmit the sensed data to a centralized entity. Transmission of data from the sensors to the centralized entity and making any decision for an application consumes a significant amount of time. Consequently, the traditional UaaS architecture is unsuitable for serving time-critical IoT applications such as transportation, healthcare, and industries. To address these issues of service latency for time-critical IoT applications, we present the FU-Serve architecture by introducing the concept of fog computing in the UaaS platform. We discuss all the components of FU-Serve elaborately in this paper. Additionally, we architect optimal and dynamic fog node selection mechanisms for FU-Serve, which reduce the transmission delay in the networks. The simulation results show that the FU-Serve outperforms by $75\%$ compared to the traditional UaaS platform.

This study genetically identified the coat color in a small wild horses’ population and compared the correspondence with the visual coat color registrations. Individual DNA from 90 Sarcidano horses was used for the genetic assignment of the coat color, to explore the correspondence with the individual form containing phenotypical traits. By genotyping and sequencing analyses of the MC1R exon 1 and ASIP exon 3, e real image of the coat color distribution in this population has been obtained. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data, in relation to coat color emerged. Genetic results showed a clear prevalence of the Chestnuts (n=58), a quite large number of Blacks (n=28) and a very small presence of Bays (n=4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Greys (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses visually identified as Bays, were genetically Blacks. This discrepancy suggests the importance of a sure coat color identification to ensure an adequate features registration, reliable also to predict the offspring’s coat color.

Fat has a high energy density and excessive fatness has been recognized as a problem for egg production and the welfare of chickens. The identification of a genetic polymorphism controlling fat deposition would be helpful to select against excessive fatness in the laying hen. This study aimed to estimate genomic heritability and identify the genetic architecture of abdominal fat deposition in a population of chickens from a Dongxiang blue-shelled local breed crossbred with the White Leghorn. A genome-wide association study wase conducted on abdominal fat percentage, egg production and body weights using a sample of 1534 hens genotyped with a 600K Chicken Genotyping Array. The analysis yielded a heritability estimate of 0.19 ± 0.04 for abdominal fat percentage, 0.56 ± 0.04 for body weight at 72 weeks, 0.11 ± 0.03 for egg production and 0.24 ± 0.04 for body weight gain. The genetic correlation of abdominal fat percentage with egg production between 60 and 72 weeks of age was 0.35 ± 0.18. This implies a potential trade-off between these two traits related to allocation of resource. Strong positive genetic correlations were found between fat deposition and weight traits. A promising locus close to COL12A1 on chromosome 3, associated with abdominal fat percent, was found in the present study. The other region located around HTR2A on chromosome 1, where allele substitution was predicted to be associated with body weight gain, accounted for 2.9% of phenotypic variance. Another region located on chromosome 1, but close to SOX5, was associated with egg production. These results may be used to influence the balanced genetic selection for laying hens.

As the COVID-19 pandemic has caused enormous damage to society, economy and public health security, it is crucial to combat the epidemic and allocate social and health resources effectively. Global optimization algorithms are extensively used in many domains to find optimal solutions to complex problems. Thus, a survey of three typical global optimizations applied on the COVID-19 pandemic is timely. This article is structured into three typical global optimization algorithms - Genetic Algorithm, Particle Swarm Optimization, and Cat Swarm Optimization - and summarizes the framework models and practical applications, as well as other optimization methods that may be applied to COVID-19. Finally, current unresolved challenges and future research opportunities to be explored are summarized.

Ornamental kale (Brassica oleracea var. acephala) is an attractive ornamental plant with a range of leaf colors and shapes. Breeding new varieties of ornamental kale has proven challenging due to its lengthy breeding cycle and the limited availability of genetic markers. Microspore culture is an effective approach to generate new materials and genetic maps are a prerequisite for quantitative trait loci analysis, MAS, fine gene mapping, and genome sequence assembly. In this study, a F1DH ornamental kale population comprising 300 DH lines was constructed using microspore culture. A high-density genetic map was developed by conducting whole-genome sequencing on 150 individuals from the F1DH population. The genetic map contained 1,696 bin-markers with 982,642 single-nucleotide polymorphisms (SNPs) spanning a total distance of 775.81 cM on all nine chromosomes with an average distance between markers of 0.46 cM. The ornamental kale genetic map contained substantially more SNP markers compared with published genetic maps for other B. oleracea crops. The F1DH progenies provide an excellent resource for germplasm innovation and breeding new varieties of ornamental kale. The high-density genetic map provides crucial insights for gene mapping and unraveling the molecular mechanisms behind important agronomic traits in ornamental kale.

The need to find the global minimum in multi-dimensional functions is a critical problem in many fields of science and technology. Effectively solving this problem requires the creation of initial solution estimates, which are subsequently used by the optimization algorithm to search for the best solution in the solution space. In the context of this article, a novel approach to generating the initial solution distribution is presented which is applied to a genetic optimization algorithm. Using the k-means clustering algorithm, a distribution based on data similarity is created. This helps in generating initial estimates that may be more tailored to the problem. Additionally, the proposed method employs a rejection sampling algorithm to discard samples that do not yield better solution estimates in the optimization process. This allows the algorithm to focus on potentially optimal solutions, thus improving its performance. Finally, the article presents experimental results from the application of this approach to various optimization problems, providing the scientific community with a new method for addressing this significant problem.

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&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;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&gt;C(p.Met1Thr) and c.449+5G&gt;A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G&gt;A. An in vitro minigene assay demonstrated that variant c.449+5G&gt;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.

Background: Obesity and Type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity plays a key role in these diseases through biological mechanisms. This study examined the effect of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.

The development of transport infrastructure is a key element of economic growth, social connectivity, and sustainable development. Many countries have historically underinvested in transport infrastructure, necessitating more efficient strategic planning in transport infrastructure investment projects implementation. This article addresses the selecting and scheduling of transport infrastructure projects, specifically within the context of drawing available resources from pre-allocated funds within a multi-annual budget investment program. The current decision-making process is largely based on expert judgment, lacking quantitative decision support methods. The authors propose a genetic algorithm as a decision-support tool that frames the problem as an NP-hard 0-1 multiple knapsack problem. The proposed genetic algorithm is unique for its matrix-encoded chromosomes, specially designed genetic operators, and a customized repair operator, which is implemented to address the large number of invalid chromosomes generated during the GA computation. The goal is to maximize the impact of allocated funds over a seven-year programming period, while respecting constraints specified by the funding authorities. In computational experiments, proposed GA is compared to an exact solution and is proved to be efficient in terms of quality of obtained solutions and computational time, highlighting its potential for enhancing strategic decision-making in transport infrastructure development.

Tamil Nadu, a state in southern India, is bereft of any native milch or dual-purpose cattle breed and the state depends chiefly on crossbred cattle for milk production. As most (90 percent) of the milk production in the state was contributed by Jersey crossbred cattle, the genetic evaluation study was intended to assess the milk production traits viz., test-day milk yields (TDMYs), total milk yield (TMY) and 305-day milk yield (305MY) in these crossbred cattle reared under farmers’ rearing environment. Data on monthly TDMYs (TDMY1 to TDMY10) of Jersey crossbred cows (n=81,653) reared by the farmers over 24 years (1999-2022) were collected for evaluation. The influence of non-genetic factors viz., location (agroclimatic zones), period and season of calving, and parity on TDMYs, TMY, and 305MY were assessed, and the variance and covariance components for genetic parameters (heritability and genetic correlation) of the traits were estimated by the method of restricted maximum likelihood (REML) under multivariate animal model and by random regression model (RRM). The overall means of various TDMYs ranged from 4.98 (TDMY10) to 9.95 kg (TDMY2) and, for TMY and 305MY the means were 2480.33 and 2393.71 kg respectively. The heritabilities estimated by animal model for TDMYs were high and ranged from 0.39 ± 0.01 to 0.47 ± 0.01 and were fairly less variable throughout the lactation while the estimates obtained by RRM were medium to high and ranged between 0.28 ± 0.01 and 0.65 ± 0.02 for different days in milk (DIMs). The heritability estimated for TMY and 305MY were 0.48 ± 0.01 and 0.49 ± 0.01 respectively. The estimates of heritability in mid-lactation yields were comparatively little less than those at the beginning and the end of lactation. The high estimates of heritabilities for TDMYs, TMY, and 305MY obtained in the present study offered an ample scope for improving milk production through selective breeding. Genetic correlations between TDMYs estimated by animal model were positive and moderate to high, with a range between 0.47 ± 0.01 and 0.99 ± 0.00. Considerably higher estimates (0.97-0.99) were observed between adjacent TDMYs showing strong genetic associations. By RRM, genetic correlations estimated between DIMs were positive, except for a few estimates and the magnitude of genetic correlation decreased with an increase in the interval between the DIMs. The high genetic correlation observed between the TDMYs in early and mid stages of lactation with TMY and 305MY suggested that these test day yields could be used favorably for the early selection of cows for milk production which facilitates reduction in the generation interval and consequently increase the annual genetic gain for the milk production traits.

To improve the current density distribution and electromagnetic performance of air-core inductors, a structural optimization method combining BP neural network and genetic algorithm was proposed for the study of axial and radial spiral multi-winding inductors. The Monte Carlo method was used to extract the structural size samples of the inductors, and the training dataset was obtained through finite element calculation of electromagnetic fields. Based on BP neural networks, nonlinear mapping models between the inductance value, volumetric inductance density, current distribution non-uniformity coefficient, and inductor structural parameters were constructed. The sensitivity analysis of the inductor inductance value affected by structural parameters was conducted through the Sobol index calculation. Using the current distribution non-uniformity coefficient as the fitness function and the volumetric inductance density as the constraint condition, the genetic algorithm was applied to optimize the structural parameters of the inductor globally. The optimization results were verified through finite element comparison. The results show that, under the requirement of satisfying the volumetric inductance density, the current distribution non-uniformity coefficient of AHI type inductor was reduced by 4.57% compared with the best sample in the sampling, while that of RHI type inductor was reduced by 5.33%, demonstrating the practicality of the BP-GA joint algorithm in the structural optimization design of inductors.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants has evolved and some of them have shown higher transmissibility becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points including the early stages of the pandemic are very crucial for understanding the evolution and transmission patterns. Using whole genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon based whole genome sequencing of randomly selected SARS-CoV-2 isolates (n=38) collected between 2020-2022 at state level VRDL, ICMR-NIRTH, Jabalpur from 11899 RT-qPCR positive samples. We observed the presence of five lineages namely B.1, B.1.1, B.1.36.8, B.1.195 and B.6 in 19 genomes from the first wave cases and variants of concern (VOC) lineages i.e. B.1.617.2 (Delta), and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern of SRAS-CoV-2 strains from the second wave in contrast to the first wave. We have identified five immune escape variants in the S gene: P681R, P681H, L452R, Q57H, and N501Y in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%), and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India.

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&gt;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.

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.