In this study, the resource blocks (RB) are allocated to user equipment (UE) according to the evolutional algorithms for long term evolution (LTE) systems. Particle Swarm Optimization (PSO) algorithm is one of the evolutionary algorithms, based on the imitation of a flock of birds foraging behavior through learning and grouping the best experience. In previous work, the Simple Particle Swarm Optimization (SPSO) algorithm was proposed for RB allocation to enhance the throughput of Device-to-Device (D2D) communications and improve the system capacity performance. In simulation results, with less population size of M = 10, the SPSO can perform quickly convergence to sub-optimal solution in the 100^th generation and obtained sub-optimum performance with more 2 UEs than the Rand method. Genetic algorithm (GA) is one of the evolutionary algorithms, based on Darwinian models of natural selection and evolution. Therefore, we further proposed a Refined PSO (RPSO) and a novel GA to enhance the throughput of UEs and to improve the system capacity performance. Simulation results show that the proposed GA with 100 populations, in 200 generations can converge to suboptimal solutions. Therefore, with comparing with the SPSO algorithm the proposed GA and RPSO can improve system capacity performance with 1.8 and 0.4 UEs, respectively.

In this paper, a thermodynamic investigation is done on a Kalina-flash cycle. This work is initially validated with the Kalina cycle power plant, Wich is commissioned in Husavic. Low-temperature Kalina-flash is considered for this study. This cycle is working with the ammonia-water mixture. The Kalina-flash cycle was optimized in the view of exergy and thermal efficiency. A multi-objective genetic algorithm is used to accomplish optimization. The optimum values of the objective functions are observed to be 40.20 and 11.70% respectively. At last, The influence of the separator inlet dryness fraction, basic ammonia mass fraction, temperature and flash pressure ratio on the first and second law efficiencies are analysed.

Accurate and efficient battery modeling is essential to maximize the performance of isolated energy systems and to extend battery lifetime. This paper proposes a battery model that represents the charging and discharging process of a lead-acid battery bank. This model is validated over real measures taken from a battery bank installed in a research center placed at “El Chocó”, Colombia. In order to fit the model, three optimization algorithms (Particle Swarm Optimization, Cuckoo Search, and Particle Swarm Optimization+Perturbation) are implemented and compared, being the last one a new proposal. This research shows that the model with the proposed algorithm is able to estimate and manage the real battery characteristics as SOC and charging/discharging voltage. The comparison between simulations and real measures shows that the model is able to absorb reading problems, signal delays, and scaling errors. The approach we present can be implemented in other types of batteries especially those used in stand-alone systems.

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.

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.

Rhodes grass (Chloris gayana Kunth) is one of the most important forage grasses used throughout the tropical and subtropical regions of the world. Enhancing the conservation and use of genetic resources requires the development of knowledge and understanding about the existing global diversity of the species. In this study, 104 Rhodes grass accessions, held in trust in the ILRI forage genebank, were characterized using DArTSeq markers to evaluate the genetic diversity and population structure, and to develop representative subsets, of the collection. The genotyping produced 193,988 SNP and 142,522 SilicoDArT markers with an average polymorphic information content of 0.18 and 0.26, respectively. Hierarchical clustering using selected informative markers showed the presence of two and three main clusters using SNP and SilicoDArT markers, respectively, with a cophenetic correction coefficient of 82 %. Bayesian population structure analysis also showed the presence of two main subpopulations using both marker types indicating the existence of significant genetic variation in the collection. A representative subset, containing 21 accessions from diverse origins, was developed using the SNP markers. In general, the results revealed substantial genetic diversity in the Rhodes grass collection and the generated molecular information, together with the developed subset, should help enhance the management, use and improvement of Rhodes grass germplasm in the future.

The Late Heavy Bombardment Period (4.1 to 3.8 billion years ago) of heightened impact cratering activity on young Earth is likely the driving force for the origin of life. During the Eoarchean, asteroids such as carbonaceous chondrites delivered the building blocks of life and water to early Earth. Asteroid collisions created innumerable hydrothermal crater lakes in the Eoarchean crust which inadvertently became the perfect cradle for prebiotic chemistry. These hydrothermal crater lakes were filled with cosmic water and the building blocks of life. forming a thick prebiotic soup. The unique combination of exogenous delivery of extraterrestrial building blocks of life, and the endogenous biosynthesis in hydrothermal impact crater lakes very likely gave rise to life. A new symbiotic model for the origin of life within the hydrothermal crater lakes is here proposed. In this scenario, life arose around four billion years ago through five hierarchical stages of increasing molecular complexity: cosmic, geologic, chemical, information, and biological. During the prebiotic synthesis, membranes first appeared in the hydrothermal crater lakes, followed by the simultaneous origin of RNA and protein molecules, creating the RNA/protein world. These proteins were noncoded protein enzymes that facilitated chemical reactions. RNA molecules formed in the hydrothermal crater basin by polymerization of the nucleotides on the montmorillonite mineral substrate. Similarly, the initial synthesis of abiotic protein enzymes was mediated by the condensation of amino acids on pyrite surfaces. The regular wet-dry cycles within the crater lakes assisted further concentration, condensation, and polymerization of the RNAs and proteins. Lipid membranes randomly encapsulated amino acids, RNA, and protein molecules from the prebiotic soup to initiate a molecular symbiosis inside the protocells, this led to the hierarchical emergence of several cell components. As the role of protein enzymes became essential for catalytic process in the RNA/protein world, Darwinian selection from noncoded to coded protein synthesis led to translation systems and the genetic code, heralding the information stage. In this stage, the biochemical pathways suggest the successive emergence of translation machineries such as tRNAs, aaRS, mRNAs, and of ribosomes for protein synthesis. The molecular attraction between tRNA and amino acid led to the emergence of translation machinery and the genetic code. tRNA is an ancient molecule that created mRNA for the purpose of storing amino acid information like a digital strip. Each mRNA strand became the storage device for genetic information that encoded the amino acid sequences in triplet nucleotides. As information became available in the digital languages of the codon within mRNA, biosynthesis became less random and more organized and directional. The original translation machinery was simpler before the emergence of the ribosome than that of today. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and adaptive theory. We believe that these three theories are not mutually exclusive, but are compatible with our coevolution model of translations machines and the genetic code. We suggest biosynthetic pathways as the origin of the translation machine that provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machinery: GNC code with four codons and four amino acids during interactions of pre-tRNA/pre-aaRS /pre-mRNA, SNS code consisting of 16 codons and 10 amino acids appeared during the tRNA/aaRS/mRNA interaction, and finally the universal genetic code evolved with the emergence of the tRNA/aaRS/mRNA/ribosome machine. The universal code consists of 64 codons and 20 amino acids, with a redundancy that minimizes errors in translation. To address the question of the origin of the biological information system in the RNA/protein world, we converted letter codons into numerical codons in the Universal Genetic Code Table. We developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa, gaining insight into how translation might have worked in the RNA/protein world. We simulated the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. We used AnyLogic software to simulate and visualize the evolution of the translation machines and the genetic code. We conclude that the emergence of the information age from the RNA/protein world was a watershed event in the origin of life about four billion years ago.

Cervical cancer is the fourth common cancer amongst women worldwide. Environmental factors such as smoking and obesity, and recurrent infection by high-risk human papillomavirus subtypes are known to promote progression towards invasive cervical disease. Infection by high-risk HPV is necessary in most cases but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability of between 27-36%, known genetic susceptibility loci that may be tumorigenic or influence host response to infection, only account for a small fraction of heritable risk factors so far. Various biobank-driven population based studies and meta-analyses have found corroborative evidence for several risk variants at the 6p21.3 locus (HLA), while many reports of variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27cm for achondroplasia (12-40cm) and 17cm for hypochondroplasia (range 10-25cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by serial 4-segment lengthenings (64 patients; both femurs and tibias same time). Most patients also had bilateral humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17-43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to increase of height into the normal height range. Previous studies showed mean increases of height of up to 20cm, while this study consistently showed an average increase of 30 cm (range 15-40cm) for juvenile-onset and increase of 26cm (range 15-30cm) for adolescent-onset. This results in lower normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12-22cm). This long-term follow-up study shows ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While the majority of cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.

Nowadays industrial dryers are used instead of traditional methods for drying. In designing dryers suitable for controlling the process of drying and reaching a high quality product, it is necessary to predict the instantaneous moisture loss during drying. For this purpose, ten mathematical-experimental models with a neural network model based on the kinetic data of pistachio drying are studied. The data obtained from the cabinet dryer will be evaluated at four temperatures of inlet air and different air velocities. The pistachio seeds will be placed in a thin layer on an aluminum sheet on a drying tray and weighed by a scale attached to the computer at different times. In the neural network, data are divided into three parts: educational (60%), validation (20%) and test (20%). Finally, the best mathematical-experimental model using genetic algorithm and the best neural network structure for predicting instantaneous moisture are selected based on the least squared error and the highest correlation coefficient.

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

Germplasm is a long-term resource management mission and investment for civilization. For both food and nutritional health, the present changing environmental scenario has become an urgent universal concern. Multiple excellent studies have been previously performed, although the advancement and innovation of practices will require the exploration of the potentiality of crop germplasm. In this study, we emphasized (i) germplasm activates, current challenges and ongoing trends of the crop germplasm, and (ii) how the system biology will be helpful to understand the complex traits such as water use efficiency (WUE), and nitrogen use efficiency (NUE) to mitigate challenges for sustainable development under growing food requirement and climate change conditions. We focused on a vision for transforming PGR into a bio-digital resource system, for the development of climate-smart crops for sustainable food production. Moreover, this review attempted to address current challenges, research gaps and describe the advanced integrated strategies that could provide a platform for future crop improvement research.

Genetic diversity is inevitable in making any crop improvement program successful. DNA fingerprinting technology to assess the genetic relationship among the selected genotypes for identification and cataloging of different species and cultivars of roses is a promising tool for Rosa genomes. The inter-simple sequence repeats markers (ISSRs) were used to investigate the genetic diversity among twenty-one diverse Rosa genotypes belonging to two different species, Rosa hybrida and R. damascena, and three distinct groups of rose varieties, namely Hybrid Tea, Floribunda, and Damask roses. Twenty-four ISSR primers yielded a total of 280 scorable amplified fragments from 250-1800 bp in length, from which 244 were polymorphic, resulting in an average of 86.4% polymorphism. UPGMA cluster analysis based on Jaccard’s pairwise similarity coefficient values ranged from 0.264 to 0.818, clearly distinguished different species and genotypes, grouping them into three distinct clusters. The results confirmed a high degree of variation in the rose germplasm studied highlighting the potential of improvement in roses for the ornamental and perfume industry.

Water distribution networks are vital infrastructure, needed for providing consumers with sufficient water of appropriate quality. The cost of construction, operation, and maintenance of such networks is extremely large. The problem of optimization of a water distribution network is governed by the type of water distribution network and the size of pipelines placed in the distribution network. This problem of the optimal diameter allocation of pipes in a distribution network has been heavily researched over the past few decades. This study describes the development of a computer program, ‘Smart Optimization Program for Water Distribution Networks’ (SOP–WDN), which applies Genetic Algorithm to the problem of the least-cost design of water distribution networks. SOP–WDN demonstrates the application of an evolutionary optimization technique, Genetic Algorithm, linked with a hydraulic simulation solver EPANET, for the optimal design of water distribution networks. The developed program was applied to three benchmark water distribution network optimization problems and produced consistently good results. SOP–WDN can be utilized as a tool for guiding engineers during the design and rehabilitation of water distribution pipelines.

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.

In industrial environments, nesting consists in cutting or extracting pieces from a material sheet, with the purpose of minimizing the surface of the sheet used. This problem is present in different types of industries, such as shipping, aeronautics, woodworking, footwear, and so on. In this work, the aim is to find an acceptable solution to solve complex nesting problems. The research developed is oriented to sacrifice accuracy for speed so as to obtain robust solutions in less computational time. To achieve this, a greedy method and a genetic algorithm have been implemented, being the latter responsible for generating a sequence for the placement of the pieces, where each piece is placed in its current optimal position with the help of a representation system for both the pieces and the material sheet.

Forensic genetic genealogy, a technique leveraging new DNA capabilities and public genetic databases to identify suspects, raises specific considerations in a law enforcement context. Use of this technique requires consideration of its scientific and technical limitations, including the composition of current online datasets, and consideration of its scientific validity. Additionally, forensic genetic genealogy needs to be considered in the relevant legal context to determine the best way in which to make use of its potential to generate investigative leads while minimising its impact on individual privacy. This article presents these issues from an Australian perspective, with the observations and conclusions likely to be applicable to other jurisdictions.

Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and brain volumes and white matter integrity (FA and MD) with magnetic resonance imaging in the BrainSCALE cohort, consisting of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years of the twins. Genes influenced externalizing behavior and changes therein (h2 up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation rph up to +0.20) and lower MD (rph up to –0.20); with sizeable genetic correlations (FA ra up to +0.42; MD ra up to –0.33). Cortical gray matter (CGM; rph up to –0.20) and cerebral white matter (CWM; rph up to +0.20) volume were phenotypically but not genotypically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence from the same genetic factor.

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital and probably appeared during biogenesis four billion years ago. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and protein molecules, drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: tRNAs, aaRS, mRNAs, and ribosomes. When assembled in the right order, the translation machine created biosynthetic polypeptides, a process that transferred information from mRNAs to proteins. This was the beginning of the prebiotic information age. The molecular attraction between tRNA and amino acids led to different stages of the translation machines and the genetic code. tRNA is an ancient molecule that designed and built mRNA for storing the information of its cognate amino acid. Each mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional. The origin of the genetic code is enigmatic; herein we propose an evolutionary explanation: the demand for a wide range of specific enzymes in the peptide/RNA world was the main selective pressure for the origin of information-directed protein synthesis. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the adaptive theory. These three theories are compatible with our coevolution model of the translation machines and the genetic code. We suggest biosynthetic pathways as the origin of the specific translation machines which provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machines: GNC code developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to understand the prebiotic information system better, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the translation might have worked in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. Using AnyLogic software we were able to simulate and visualize the entire evolution of the translation machines and the genetic code. The results indicate that the emergence of the information age from the peptide/RNA world was a watershed event in the origin of life about four billion years ago.

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.

The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). “Superwobbling” or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

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

The 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.

The article shows materials to the question about algebraic features of the genetic code and about the dictatorial influence of the DNA and RNA molecules on the whole organism. Presented results testify in favor that the genetic code is an algebraic code related with a wide class of algebraic codes, which are a basis of noise-immune coding of information in communication technologies. Structural features of the genetic systems are associated with hypercomplex double (or hyperbolic) numbers and with bisymmetric doubly stochastic matrices. The received results confirm that represented matrix approaches are effective for modeling genetic phenomena and revealing the interconnections of structures of biological bodies at various levels of their organization. This allows one to think that living organisms are algebraically encoded entities where structures of genetic molecules have the dictatorial influence on inherited structures of the whole organism. New described algebraic approaches and results are discussed.

Parkinson’s disease (PD) is the most common cause of movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. It is increasingly recognized as a complex group of disorders presenting widely heterogenous symptoms and pathology. Except for the rare monogenic forms, the majority of the PD cases result from an interaction between multiple genetic and environmental risk factors. The search for these risk factors and the development of preclinical animal models are in progress hand in hand, providing mechanistic insights into the pathogenesis of PD. This review summarizes the studies that capitalize on modeling sporadic (i.e. non-familial) PD using Drosophila melanogaster and discuss their methodology, new findings and future perspective.

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.

There are many theories of carcinogenesis arguing against the orthodox mutation theory, debating on such as “epigenetic alteration” that is inheritable and yet, theoretically, reversible. Our integrated theory describes that any extracellular, intracellular, or intranuclear stressors, mutagenic or not, can initiate a lengthy tumorigenesis to engender a benign or malignant tumor, but the aberrations directly establishing cellular immortality and autonomy may be epigenetic or genetic alterations in the genomic DNA. A neoplasm is considered a semi-new organism with autonomy; it therefore should have genetic mutations to be “new”. We may be able to direct cancer cells towards differentiation as a remedy, because the extracellular milieu may control the phenotype of a cell and the tissue or organ made of the cell’s progenies, and the cytoplasm of a cell may override the nucleus in the phenotypic control. However, the nucleus retains the capacity to manifest itself if allowed by the microenvironment, which then allows the already reversed cells to revert back to tumor cells again. Neoplasms are malignant if they bear epigenetic or genetic anomalies in mutator genes defined as those whose alterations allow or accelerate alterations to occur in other genes, whereas neoplasms are benign if they bear epigenetic or genetic aberrations only in non-mutator genes. It is imperative to identify the immediate tumor-causing cellular alterations defined as those directly responsible for immortality and autonomy, and for treatment purposes to identify the extracellular and intracellular factors that control the phenotype of cancer cells.

Germplasm is a valuable natural resource in plant diversity that is crucial for its potential use. It provides knowledge about a species genetic composition. Germplasm protection strategies are not just planting hope threatened with extinction, they preserve medicinal and other essential plants on which survival rests. The successful use of genetic plant resources necessitates diligent collection, storage, analysis, documentation, and germplasm exchange. Slow growth cultures, cryopreservation, pollen and DNA banks, botanic gardens, genetic reserves and farmer’s fields are few conservation techniques. However, usage of an in vitro procedure with any chance of genetic instability leads to the destruction of the entire substance. Improved understanding of basic regeneration biology would, in turn, undoubtedly increase the capacity to regenerate plants from in vitro harvested explants, thus expanding selection possibilities. Germplasm conservation seeks to conserve endangered and vulnerable plant species worldwide for future proliferation and development; it is also the bedrock of agricultural production.

Wheat (Triticum aestivum L.) breeding programs can take over a decade to release a new variety. However, new methods of selection such as genomic selection (GS) must be integrated to decrease the time it takes to release new varieties to meet the demand of a growing population. The implementation of GS into breeding programs is still being explored, with many studies showing its potential to change wheat breeding through achieving higher genetic gain. In this review, we explore the integration of GS for a wheat breeding program by redesigning the traditional breeding pipeline to implement GS. We propose implementing a two-part breeding strategy by differentiating between population improvement and product development. The implementation of GS in the product development pipeline can be integrated into most stages and can predict within and across breeding cycles. Additionally, we explore optimizing the population improvement strategy through GS recurrent selection schemes to reduce crossing cycle time and significantly increase genetic gain. The recurrent selection schemes can be optimized for parental selection, maintenance of genetic variation, and optimal cross-prediction. Overall, we outline the ability to increase the genetic gain of a breeding program by implementing GS and a two-part breeding strategy.

The prevalence of algorithms and computational tools in the modern-day has intersected with nearly every field. Generative design, specifically those using genetic algorithms, is an increasingly effective, yet cost efficient way to generate architectural designs in modern engineering. Thus, we adopt a genetic algorithm model in pursuit of maximizing the durability of a structure when it is stressed while minimizing the material cost. After the model is formulated, the algorithm is able to approximate with high accuracy the load a small-scale structure is able to bear, as well as iterate upon its designs to maximize a fitness function.

Pig genetic resources in Africa originate from different regions. Genetic analysis has shown a strong phylogeographic pattern with the pigs on the eastern parts showing a high frequency of alleles from the Far East while the ones on the western parts show a strong European influence. This highlights the influence of trade routes on the genetic legacy of African pigs. They have, however, since adapted to the local environments to produce unique populations with unique attributes. Most of the pigs are now reared in resource-constrained smallholdings under free-range conditions. They are largely owned by women who spread ownership of the resource through kinship networks. Very little work has been done to characterize, conserve and sustainably utilize pig genetic resources in Southern Africa. The risk status of the breeds together with population numbers, distribution and other attributes are largely unknown. This paper proposes several strategies for the sustainable utilization of the pig genetic resources: a market-driven in situ conservation program and two complementary ex situ strategies. In addition, the possibility of community-based breed improvement programs is discussed.

Study in black rice has gain prominence in recent times due to its high nutritive value, curative effect, and anti-oxidant properties. However, its poor agronomic traits, including low yield necessitates the incorporation of the colour-grain trait into elite varieties through plant breeding techniques. SSR markers play an important role in plant identification and breeding. Here, the generation of reference-based transcriptome, annotation of transcriptome datasets, and a large set of simple sequence repeat (SSR) markers derived from Black rice have been described. In all 28664 SSRs were predicted in 34978 (48.59%) expressed transcripts. However, 7068 (20.20%) transcripts were found to have more than one SSR. The identified SSRs were dominated by tri-nucleotide and tetra-nucleotide repeats representing about 54.11% and 33.31% respectively, of total SSRs. Validation of selected markers associated with anthocyanin trait performed across different black rice accessions established the reliability of the process used for mining SSR markers. The SSR markers identified in this study could be used to select varieties with desired traits, and to investigate the genetic mechanism underlying anthocyanin accumulation in the pericarps of black rice. Furthermore, the findings from this study may prove beneficial in future genetic diversity studies, primer development, and selective breeding programs.

The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options for tested individuals and their family members. We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing with positive reports. We reviewed positive results with respect to the different levels of information provided in the reports; risk estimation and management, cascade family testing, information from secondary findings and actionable information for treatment decision-making. A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high (BRCA1, BRCA2, PALB2, PTEN, TP53), moderate (ATM, CHEK2, NBN), low (BARD1, BRIP1, CHEK2, MLH1, MSH2, MSH6, NF1, RAD51C) and with insufficient evidence for breast cancer risk genes (FANCA, FANCM, NBN, MRE11, PMS2, RAD50, RAD51B, XRCC2, MUTYH), respectively. 6.7% of individuals were double heterozygotes with two pathogenic variants. Germline findings in 92% of individuals are linked to evidence-based treatment information and receive risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.

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

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

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Epimutations are the cause of a considerable number of genetically inherited conditions in humans. All result from the mis-expression of genes due to epigenetic changes that are triggered by an underlying heritable mutation. The correction of these epigenetic defects in the context of epigenetically regulated diseases constitutes a good paradigm to probe the fundamental mechanisms underlying the development of these diseases, and the molecular basis for the establishment, maintenance and regulation of epigenetic modifications in general. Here, we review current applications of key editing tools to address the epigenetic aspects of these diseases by focusing on epimutations caused by, or relate to repetitive elements, primarily unstable noncoding repeat expansions. For each approach we summarize the efforts conducted to date, highlight their contribution to a better understanding of the molecular basis of epigenetic mechanisms, describe the limitations of each approach and suggest perspectives for further exploration in this field.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

Gas sensor arrays, also known as electronic noses, leverage a diverse set of materials to identify the components of complex gas mixtures. Metal-organic frameworks (MOFs) have emerged as promising materials for electronic noses due to their high-surface areas and chemical as well as structural tunability. Using our recently reported genetic algorithm design approach, we examined a set of 50 MOFs and searched through the over 1.125x1015 unique array combinations to identify optimal arrays for the detection of CO₂ in air. We found that despite individual MOFs having lower selectivity for O2 or N2 relative to CO₂, intelligently selecting the right combinations of MOFs enabled accurate prediction of the concentrations of all components in the mixture (i.e. CO₂, O₂, N₂). We also analyzed the physical properties of the elements in the arrays to develop an intuition for improving array design. Notably, we find that diversity among the surface areas in the MOFs leads to improved sensing. Consistent with the observation, we found that, as one might expect, the best arrays consistently had more structural diversity than the worst arrays.

Repeat-Induced Point mutations (RIP) serves as a genome defence mechanism that impedes the deleterious consequences of repeated motifs such as transposable elements in fungi. Genomic regions with RIP are biased for adenosine and thymine transitions and the cumulative influence of RIP is thought to have a considerable impact on genome composition. We investigated the impact of RIP on localized genomic regions and whole-genome sequences for representatives of the pine pathogen, Fusarium circinatum. We set out to determine the intraspecific variation in acquired RIP and the role of RIP in the development of diverse F. circinatum sub-genomic compartments. The results of the study show that the AT-enriched sub-genomic compartment accounts for ca. 97% of the calculated RIP and was further prominent in both core and accessory genomic regions. However, more extensive RIP was observed in the accessory sub-compartment and more variable regions of the genome. Regions with RIP indicated increased intrinsic curvature of the DNA which may influence DNA-protein interactions and may promote constitutive heterochromatin formation. The results show that RIP is an important source of functional novelty and genome variation. RIP contributes to the evolution of the genetic landscape and differentiation of diverse sub-genomic compartments of this important fungal pathogen.

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made on complex multicellular organisms, and then modified to fit a DNA-centric view. In this article, I argue that, based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that: i) natural selection plays a dominant role in evolution, and ii) the probability of mutations is independent of the generated phenotype. I will show that the adaptation of a phenotype to an environment does not correspond to organism fitness but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome, and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype, the phenotype ensuring the stability of the genotype in a cellular and environment physicochemical parameter-depending manner.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

A protocol was designed for plasmid curing using a novel counter-selectable marker, named pylSZK-pylT, in Escherichia coli. The pylSZK-pylT marker consists of the archaeal pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl) with modification, and incorporates an unnatural amino acid (Uaa), Nε-benzyloxycarbonyl-l-lysine (ZK), at a sense codon in ribosomally synthesized proteins, resulting in bacterial growth inhibition or killing. Plasmid curing is performed by exerting toxicity on pylSZK-pylT located on the target plasmid, and selecting only proliferative bacteria. All tested bacteria obtained using this protocol had lost the target plasmid (64/64), suggesting that plasmid curing was successful. Next, we attempted to exchange plasmids with the identical replication origin and an antibiotic resistance gene without plasmid curing using a modified protocol, assuming substitution of plasmids complementing genomic essential genes. All randomly selected bacteria after screening had only the substitute plasmid and no target plasmid (25/25), suggesting that plasmid exchange was also accomplished. Counter-selectable markers based on PylRS-tRNApyl, such as pylSZK-pylT, may be scalable in application due to their independence from the host genotype, applicability to a wide range of species, and high tunability due to the freedom of choice of target codons and Uaa’s to be incorporated.

Keyhole neurosurgery implies reaching a target area inside the brain through an entry point specified by the neurosurgeon. In order to avoid complications, a risk assessment procedure must be done to establish the minimum risk trajectory from the entry point to the target area. The neurosurgeon establishes the risk values for the brain structure according to the type of intervention. The preset brain structure risk value is used to assess the risk value for each voxel of the brain. This paper proposes an improved risk assessment methodology based on the sum of N maximum risk values for each voxel. Then, risk assessment for a trajectory is done by adding the risk of all voxels that are part of the path. The safest trajectory is defined as the trajectory with the lower risk. Our proposed search trajectory methodology includes a Genetic Algorithm (GA) for finding the safest trajectories. The use of a GA drastically reduces the number of trajectories to analyze, speeding up the planning procedure. The achieved results were qualified by expert neurosurgeons as satisfactory. Our proposed method allows neurosurgeons to calibrate the surgical planning system by allowing them to establish the risk brain structure and the risk value for each structure.

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response, and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular, comprehensive follow up is necessary.

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.

Saccharomyces cerevisiae are a phenotypically diverse species that adapt to a wide variety of environments by exploiting standing genetic diversity and selecting for advantageous mutations. Glyphosate and copper-based herbicides/ fungicides affect non-target organisms, these incidental exposures can impact microbial populations. In this study, glyphosate resistance was found in the historical collection of yeast which was collected over the last century, but only in yeast isolated after the introduction of glyphosate. The highest glyphosate-resistant yeasts were isolated from agricultural sites. However, herbicide application at these sites was not recorded. In an effort to assess glyphosate resistance and impact on non-target microorganisms, yeast were harvested from 15 areas with known herbicidal histories, including an organic farm, conventional farm, remediated coal mine, suburban locations, state park, and a national forest. Yeast representing 23 genera were isolated from 237 samples of plant, soil, spontaneous fermentation, nut, flower, fruit, feces, and tree material samples. Saccharomyces, Candida, Metschnikowia, Klyveromyces, Hanseniaspora, and Pichia were other genera commonly found across our sampled environments. Managed areas had less species diversity and at the brewery, only Saccharomyces and Pichia were isolated. A conventional farm growing RoundUp Ready™ corn had the lowest phylogenetic diversity and the highest glyphosate resistance. The mine was sprayed with multiple herbicides including a commercial formulation of glyphosate; however, the yeast did not have elevated glyphosate resistance. In contrast to the conventional farm, the mine was exposed to glyphosate only one year prior to sample isolation. Glyphosate resistance is an example of the anthropogenic selection of nontarget organisms.

Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or better as left ventricular apical balloon syndrome in the recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by the strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the reduced understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in the last years, and particularly correlated to SARS-CoV-2 pandemic, leads us to imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial form of TTS has been described. But a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we, here, conducted a systematic review of literature before June 2021, to contribute to identify potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but of reduced number and with diverse limitations. Consequently, we concluded further work is needed to address the gaps discussed, and probably a clear evidence may arrive using multi-omics investigations.

The Vehicle Routing Problem (VRP) and its variants are found in many fields, especially logistics. In this study, we introduced an adaptive method to a complex VRP. It combines multi-objective optimization and several forms of VRPs with practical requirements for an urban shipment system. The optimizer needs to consider terrain and traffic conditions. The proposed model also considers customers' expectations, shipper considerations as goals, and the common goal like transportation cost. We offered compromise programming to approach the multi-objective problem by decomposing the original multi-objective problem into a minimized distance-based problem. We designed a hybrid version of the Genetic algorithm with the Local Search algorithm to solve the proposed problem. We evaluate the effectiveness of the proposed algorithm with the Tabu Search algorithm, the original Genetic algorithm on the tested dataset. The results show that our method is an effective decision-making tool for the multi-objective VRP and an effective solver for the new variation of VRP.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

PEM fuel cell is a technology successfully used in the production of energy from hydrogen, allowing the use of hydrogen as an energy vector. It is scalable for stationary and mobile applications. However, the technology demands more research. An important research topic is fault diagnosis and condition monitoring to improve the life and the efficiency and to reduce the operation costs of PEMFC devices. Consequently, there is a need of physical models that let deep analysis. These models must be accurate enough to represent the PEMFC behavior and to allow the identification of different internal signals of a PEM fuel cell. This work presents a PEM fuel cell model that uses the output temperature in a closed loop, so it can represent the thermal and the electrical behavior. The model is used to represent a NEXA Ballard 1.2 kW; therefore it is necessary to fit the coefficients to represent the real behavior. Five optimization algorithms were tested to fit the model, three of them were taken from literature and two were proposed. Finally, the model with the parameters identified was validated with real.

Promoter is a small region of DNA sequence in response to various transcription factors, which initiates a particular gene expression. The promoter-engineered bio-sensor can activate or repress gene expression through transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids or redox molecule, however, the reported applications of promoter enhanced bio-sensor are not too much. This review paper highlights the strategies of construction of promoter-gene engineered bio-sensor with human and bacteria’s genetic promoter array for high-throughput screening (HTS) molecular drugs, study of membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factor, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These bio-sensors’s sensitivity and specificity can be further improved by proposed approaches of Mn²⁺ and Mg²⁺ added random Error-prone PCR and site-directed mutagenesis which is applied for construction of bacteria’s “mutant library”. It is expected to establish flexible HTS platform (Bio-sensor array) to large-scale screen transcription factor-acting drugs, reducing the toxicity of intermediate compounds, and constructing gene dynamic regulatory system in “push and pull” mode to effectively regulate the valuable medicinal product production. This proposed novel promoter-engineered biosensors aided synthetic genetic circuit construction will maximize the efficiency of bio-synthesis of medicinal compound, which will greatly promote the development of microbial metabolic engineering and biomedical science.

Genetic switches can be utilized for many purposes in synthetic biology including the assembly of complex genetic circuits to achieve sophisticated cellular systems and the construction of biosensors for real-time monitoring of intracellular metabolite concentrations. Although genetic switches have mainly been developed in prokaryotes to date, eukaryotic genetic switches are increasingly being reported as both rational and irrational engineering technologies mature. In this review, we describe genetic switches in yeast based on synthetic transcription factors and/or synthetic promoters. We also discuss directed evolution technologies for the rapid and robust construction of yeast genetic switches.

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market, and rapid analysis of the resulting genotype data can now have significant impact. We present a method for summarizing personal genotypes as ‘genotype fingerprints’ that meet these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism (SNP)-based assay, and remain comparable as chip designs evolve to higher marker densities. We demonstrate that they support distinguishing types of relationships among closely related individuals and closely related individuals from individuals from the same background population, as well as high-throughput identification of identical genotypes, individuals in known background populations, and de novo separation of subpopulations within a large cohort through extremely rapid comparisons. While fingerprints do not preserve anonymity, they provide a useful degree of privacy by summarizing a genotype in a way that prevents reconstruction of individual marker states. Genotype fingerprints are therefore well-suited as a format for public aggregation of genetic information to support ancestry and relatedness determination without revealing personal health risk status.

One of the most important subjects of hydraulic engineering is the reliable estimation of the transverse distribution in rectangular channel of bed and wall shear stresses. This study makes use of the Tsallis entropy, Genetic Programming (GP) and (ANFIS) methods to assess the shear stress distribution (SSD) in rectangular channel. To evaluate the results of the Tsallis entropy, GP and ANFIS models, laboratory observations were used in which shear stress was measured using an optimized Preston tube. This is then used to measure the SSD in various aspect ratios in the rectangular channel. To investigate the shear stress percentage, 10 data series with a total of 112 different data for were used. The results of the sensitivity analysis show that the most influential parameter for the SSD in smooth rectangular channel is the dimensionless parameter B/H, Where the transverse co-ordinate is B, and the flow depth is H. With the parameters (b/B), (B/H) for the bed and (z/H), (B/H) for the wall as inputs, the modeling of the GP was better than the other one. Based on the analysis, it can be concluded that the use of GP and ANFIS algorithms is more effective in estimating shear stress in smooth rectangular channels than the Tsallis entropy-based equations.

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 last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

Using morphological characteristics and SSR markers, we evaluated the morphological and genetic variation of 200 Perilla accessions collected from the five regions of South Korea and other region. In morphological characteristics analysis, particularly, leaf color, stem color, degree of pubescence, leaf size were found to be useful for distinguishing the characteristics of native Perilla accessions cultivated in South Korea. A total of 137 alleles were identified in the 20 simple sequence repeat (SSR) markers, and the number of alleles per locus ranged from 3 to 13, and the average number of alleles per locus was 6.85. The average gene diversity (GD) was 0.649, with a range of 0.290-0.828. From analysis of SSR markers, accessions from the Jeolla-do and Gyeongsang-do regions showed comparatively high genetic diversity values compared with those from other regions in South Korea. In the unweighted pair group method with arithmetic mean (UPGMA) analysis, the 200 Perilla accessions were found to cluster into three major groups and an outgroup with a genetic similarity of 42%, and did not showed a clear geographic structure from the five regions of South Korea. Therefore, it is believed that landrace Perilla seeds are frequently exchanged by farmers through various routes between the five regions of South Korea. The results of this study are expected to provide useful information for conservation of these genetic resources and selection of useful resources for the development of varieties for seeds and leafy vegetables of cultivated var. frutescens of Perilla crop in South Korea.

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-azacytidine (5azaC) is a potent mutagen for template-switching, dependent on DNA cytosine methylase (Dcm), implicating the trapped Dcm-DNA covalent complex as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require DSB repair via RecABCD. The ability to induce the SOS response is anti-mutagenic by an unknown mechanism. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.

The corrugated board is a versatile and durable material that is widely used in the packaging industry. Its unique structure provides strength and cushioning, while its recyclability and bio-degradability make it an environmentally friendly option. The strength of corrugated board depends on many factors, including the type of individual papers on flat and corrugated layers, the geometry of the flute, temperature, humidity, etc. This paper presents a new approach to analysis geometric features of corrugated boards based on the images. It allows for precise determination of the geometry of the corrugated layer, as well as the thickness of individual papers in all cardboard layers. The experimental set used in the work and the created software are characterized by high reliability and precision of measurement thanks to the use of an identification procedure based on image analysis and evolutionary algorithms. This allows to quickly find the main geometric characteristics of the corrugated board, which in turn leads to the possibility of performing numerical analyzes taking into account the real model of the corrugated board. Calculations made on a real (correctly mapped geometrically) model allow, for example, a more reliable analysis of the composition of the cardboard, and thus also to obtain greater savings in the optimization process.

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

Evaporation from surface water plays a key role in water accounting of basins, water resources management, and irrigation systems management, so simulating evaporation with high accuracy is very important. In this study, two methods for simulating pan evaporation under different climatic conditions in Iran were developed. In the first method, six experimental relationships (linear, quadratic, and cubic, with two input combinations) were determined for Iran’s six climate types, inspired by a multilayer perceptron neural network (MLP-NN) neuron and optimized with the genetic algorithm. The best relationship of the six was selected for each climate type, and the results were presented in a three-dimensional graph. In the second method, the best overall relationship obtained in the first method was used as the basic relationship, and climatic correction coefficients were determined for other climate types using the genetic algorithm optimization model. Finally, the accuracy of the two methods was validated using data from 32 synoptic weather stations throughout Iran. For the first method, error tolerance diagrams and statistical coefficients showed that a quadratic experimental relationship performed best under all climatic conditions. To simplify the method, two graphs were created based on the quadratic relationship for the different climate types, with the axes of the graphs showing relative humidity and temperature, and with pan evaporation was drawn as contours. For the second method, the quadratic relationship for semi-dry conditions was selected as the basic relationship. The estimated climatic correction coefficients for other climate types lay between 0.8 and 1 for dry, semi-dry, semi-humid, Mediterranean climates, and between 0.4 and 0.6 for humid and very humid climates, indicating that one single relationship cannot be used to simulate pan evaporation for all climatic conditions in Iran. The validation results confirmed the accuracy of the two methods in simulating pan evaporation under different climatic conditions in Iran.

Abstract: A large number of collecting expeditions were launched in regions of ‘centers of diversity’ and hundreds of thousands of sample have been collected and stored in gene banks as ‘genetic resources’. So far, only a small number of the samples have been evaluated for their biotic and abiotic stress tolerance. Now, their time to become useful has come. A new global phenomenon has arisen – climate change. The crop genetic resources and their wild progenitors that have survived countless years of changing environment during the last 11,000 years could harbor genes that may be useful under the new growing conditions and environmental factors thrown up by climate change and global warming. With the deployment of modern bio-engineering techniques selected genes or gene fragments can be transferred from genetic resources to modern varieties of crop plants to make them well-prepared to mitigate the effects of global warming and climate change. The latter is the most serious issue facing plant breeders today. New pests and diseases could affect crop production. These review paper discusses various impacts and issues as a result of this phenomenon and suggest ways to safeguard our most important crops through better management of crop plant genetic resources in the near future.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one “actionable” variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

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.

Gut protozoan parasites are neglected and not targeted by specific control initiatives and this have led to a knowledge gap concerning their regional diversity and epidemiology. The present study aims to explore Giardia duodenalis genetic diversity and assess the epidemiologic scenario of subclinical infections in different Brazilian biogeographic regions. Cross-sectional surveys (n=1,334 subjects) were conducted in the Amazon, Cerrado, Semiarid and Atlantic Forest. Microscopy of non-diarrheal feces and nucleotide sequencing of a β-giardin gene fragment were performed. Twenty-seven (52.9%) β-giardin sequences were characterized as assemblage A and 24 (47.1%) as assemblage B. In Amazon, assemblage B was the most frequently detected with 2 novel sub-assemblages. Assemblage A predominated in the extra-Amazon region, with 5 novel sub-assemblages. Prevalence rates reached 17.8% in Amazon, 8.8% in Atlantic Forest, 7.4% in Cerrado and 2.3% in the Semiarid. People living in poverty and extreme poverty presented significantly higher positivity rates, reaching 11.9% and 14.5%, respectively. Giardiasis tended to be more frequent in stunted (21.6%) than in eutrophic children (12.9%). In conclusion, subclinical giardiasis in endemic in Brazilian communities in different biogeographic regions, presenting high genetic diversity and a heterogeneous genotypic distribution.

The present cultivated enset clonal landraces in Ethiopia originated from few wild progenitors. However, enset has a mixed mode of reproduction in which, the wild enset reproduces sexually through seeds, while cultivated enset is generally propagated vegetatively. The objective of this study was to understand the genetic structures of enset cultivars and estimate their genetic variability by evaluating the morphological data generated from progenies of cultivated and wild enset clones. Hence, seeds collected from six cultivated and four wild enset genotypes were used for this study. Data on four qualitative and six quantitative morphological traits were recorded from the progenies of the 10 enset genotypes. Progenies of seven enset genotypes segregated with 3:1 genetic ratio while progenies of the remaining genotypes segregated differently for the qualitative traits considered. With regard to the quantitative traits, the progenies of the 10 enset genotypes differed significantly for five of the six traits except pseudostem length. Generally the cultivated clones performed better than the wild types. This study demonstrated the possibility of creating genetic variation through selfing of the existing clones of enset for traits of interest and makes improvements either through selection or crossing the elite types to develop novel cultivar

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

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 article explains how resistance alleles have become rare or have disappeared from honey bee populations in Europe (and probably also in North America). Honeybees have the highest recombination frequency of all animals, indicating that pathogenic bacteria, viruses, fungi and microsporidia are an important source of selection. To respond to new virulent strains of pathogens, honeybees need to have access to rare alleles that could foster immunity against a new pathogen. By mating in a large panmictic population, new rare alleles can be recruited, which can then be combined into new genotypes through recombination with useful alleles of other genes. Bee breeders, by selecting small samples from a large population tend to select common alleles and lose the rare ones. Rare alleles can become important when a new virulent pathogen arrives. The loss of rare alleles makes bees vulnerable to disease and parasites and explains, together with the problems caused by modern agriculture, why managed bees have high mortality rates.

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.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

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.

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

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.

The article studies the Venetsiansky (Hydropark) Island (the Dnipro River, Kyiv, Ukraine) landscape structure applying the genetic landscape science method and the European landscape classification (LANMAP) approach. The aim of the article is to determine the best way to study the river islands landscapes analyzing the Venetsiansky Island landscape structure by the both methods. Methodology. The genetic landscape science method consists in the next steps: 1) the island’s territory information collecting; 2) the preliminary landscape map creating; 3) field study; 4) the final landscape map creating. The LANMAP method consists on: 1) the climate study; 2) the altitude study; 3) the parent material study; 4) the land cover study. The results. The genetic landscape science method demonstrates that the Venetsiansky Island is not a landscape, but a structural part of the landscape – the tract. The LANMAP study reveals that the Venetsiansky Island is naturally homogeneous, but land cover differs. The conclusion. The both methods’ study shows that the river island cannot be the entire landscape by the natural criteria, but only the part of it. The genetic landscape science explores the landscape forming while the LANMAP reveals the current state of the landscape.

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.

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 current industrial landscape, increasingly pervaded by technological innovations, the adoption of optimized strategies for asset management is becoming a critical key success factor. Among the various strategies available, the “Prognostics and Health Management” strategy is able to support maintenance management decisions more accurately, through continuous monitoring of equipment health and “Remaining Useful Life” forecasting. In the present study, Convolutional Neural Network-based Deep Neural Network techniques are investigated for the Remaining Useful Life prediction of a punch tool, whose degradation is caused by working surface deformations during the machining process. Surface deformation is determined using a 3D scanning sensor capable of returning point clouds with micrometric accuracy during the operation of the punching machine, avoiding both downtime and human intervention. The 3D point clouds thus obtained are transformed into bidimensional image-type maps, i.e., maps of depths and normal vectors, to fully exploit the potential of convolutional neural networks for extracting features. Such maps are then processed by comparing 15 genetically optimized architectures with the transfer learning of 19 pre-trained models, using a classic machine learning approach, i.e., Support Vector Regression, as a benchmark. The achieved results clearly show that, in this specific case, optimized architectures provide performance far superior (MAPE=0.058) to that of transfer learning which, instead, remains at a lower or slightly higher level (MAPE=0.416) than Support Vector Regression (MAPE=0.857).

: Urinary schistosomiasis caused by the parasite Schistosoma haematobium is the most common form of schistosomiasis. This parasite has a high potential for genetic exchange within parasite populations giving rise to the genetic diversity that is important for its survival. Genetic differ-ences may lead to some parasite strains being more immunogenic which may have a negative impact on management and control of schistosomiasis. Therefore, understanding these genetic differences in the parasite may lead to better management of the disease. A literature search was done on PubMed, African Journals online and Google scholar using predefined search terms such as urinary schistosomiasis, S. haematobium, genetic diversity in sub-Saharan Africa in com-bination with Boolean operators (AND, OR). The search included studies published from 2000-2020 that emphasised on genetic diversity of Schistosoma haematobium in sub-Saharan Africa. Sixteen studies from 18 sub-Saharan African countries that met the inclusion criteria were se-lected. Most studies conducted in these countries showed a high genetic diversity of Schistosoma haematobium studies with microsatellite markers being the most commonly used method for ge-netic diversity determination. Fisher’s exact test showed that the distribution of genetic diversity in sub-Saharan African regions was not statistically significant (p=0.768). The highest number of studies on genetic diversity of Schistosoma haematobium were conducted in West Africa with Ni-geria and Zimbabwe in Southern Africa conducting the most studies, 4/36 (11%) each. Results obtained show the need for continued monitoring of genetic variations in Schistosoma haemato-bium in sub- Saharan Africa. This will aid in understanding the epidemiology of disease, ad-vancing novel treatment and vaccine strategies.

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

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.

Plankton monitoring by microscopy offers long-term ecological perspective of plankton communities but is biased towards those organisms that can be distinguished using the microscope. Genetic identification of marine plankton has become standard but is still not used. This study is a comprehensive study genetically measured taxa in the Western Channel of UK using a small-volume automated water sampler deployed on the CPR platform. The study present one year of high-throughput sequencing data focussing on smaller plankton and separate community to that measured by microscopy that can complement each other for a holistic view of plankton. Quantitative tests of two harmful algae show relatively high abundance of the Pelagophyte Aureococcus anophagefferens during 2011 with low nitrite levels. Three years of Pseudo-nitzschia delicatissima quantitative monitoring also shows a greater abundance of this potentially harmful taxa in 2011. Flow cytometry reveals distinct seasonal cycles with distinct timings.

Dalbergia sissoo (shisham), an important timber yielding multipurpose tree species of the Indian subcontinent, has been afflicted with large scale mortality due to wilt in natural forests and plantations, causing huge economic losses. Fusarium solani f. sp. dalbergiae (Fsd) has been identified as one of the causal organisms for wilt disease in D. sissoo. Present study comprises in vitro screening of ten selected genotypes of D. sissoo against two strains of Fsd in a dual culture set up under axenic condition. Callus and plantlets of ten genotypes of host plant were multiplied in vitro and were inoculated with conidial suspension of two strains of Fsd at three concentrations; 1× 10¹, 1× 10³, and 1× 10⁵ conidia/ml. Gnotobiotic evaluation of dual culture set up shows variations among D. sissoo genotypes in their response towards in vitro Fsd infection; and two genotypes (14 and 66) exhibited resistance against the pathogen strains. Callus of genotypes 14 and 66 significantly restricted the fungal mycelium growth whereas callus of remaining eight genotypes were completely infested by Fsd mycelium within 9 days. Similarly, plantlets of genotype 14 and 66, had lesser disease severity and remained green, and had fewer necrotic lesions in the roots whereas plantlets of remaining eight genotypes died within 15 days.

Understanding the mechanism, how entirely new (EntNew) gene/protein or the first ancestral gene/protein of a family was created, should be one of the most important issues in the biological sciences. However, the mechanism is totally unknown still now. On the other hand, it is well known that mature protein is generally rigid and one catalytic center exists on the protein. Creation of such a mature EntNew gene/protein should be, of course, carried out through random process, because it cannot be designed in advance. However, the EntNew gene/protein never be created by random polymerization of the respective monomeric units, because of the extraordinary large sequence diversities of ~10¹⁸⁰ and ~10¹³⁰, respectively. Protein 0^th-order structure or a specific amino acid composition, in which immature but water-soluble protein can be produced even through random process, holds the key for solving the difficult problem. As it was fragmentally described in the previous papers how and where EntNew gene/protein was created, I describe in detail in this review three processes generating EntNew gene/protein with some flexibility under three genetic codes, the universal genetic code, SNS primitive code and GNC primeval code, and discuss why the mature gene/protein could be created through the processes.

Plant height is significantly correlated with grain traits, which is a component of wheat yield. The purpose of this study is to investigate the main QTLs that control plant height and grain-related traits in multiple environments. In this study, we constructed a high-density genetic linkage map using the Wheat50K SNP Array to map quantitative trait loci (QTLs) for these traits in 198 recombinant inbred lines (RILs). The two ends of the chromosome were identified as re-combination-rich areas in all chromosomes except chromosome 1B. The middle area of the chro-mosomes was identified as the recombination-barren area. Both the genetic map and the physical map showed a significant correlation when p=0.001, with a correlation coefficient between 0.63 and 0.99. However, there was almost no recombination between 1RS and 1BS. In terms of plant height, 1RS contributed to the reduction of plant height by 3.43cm. In terms of grain length, 1RS contributed to the elongation of grain by 0.11mm. A total of 43 QTLs were identified, including 8 QTLs for Plant height(PH), 11 QTLs thousand grain weight(TGW), 15 QTLs for grain length(GL),and 9 QTLs for grain width(GW), which explained 1.36%–33.08% of the phenotypic variation. Seven were environment-stable QTLs, including two loci Qph.nwafu-4B and Qph.nwafu-4D that determined plant height. The explanation rates of phenotypic variation were 7.39%-12.26% and 20.11%-27.08%, respectively. One QTL, Qtgw.nwafu-4B, which influenced TGW, showed an explanation rate of 3.43%-6.85% for phenotypic variation, two co-segregating KASP markers were developed, the physical locations corresponding to KASP_AX-109316968 and KASP_AX-109519968 were 25.888344 MB and 25.847691 MB. Another QTL, Qgw.nwafu-4D, which determined grain width, had an explanation rate of 3.43%-6.85%. Three loci that affected the grain length were Qgl.nwafu-5A, Qgl.nwafu-5D.2 and Qgl.nwafu-6B, illustrating the explana-tion rates of phenotypic variation as 6.72%-9.59%, 5.62%-7.75%, and 6.68%-10.73%, respectively. Two QTL clusters were identified on chromosomes 4B and 4D.

Tick borne encephalitis virus (TBEV) is the causative agent of Tick borne encephalitis in humans, a severe zoonosis occurring in the Paleartic region mainly transmitted through ticks belonging to the genus Ixodes. In Italy, TBEV is restricted to few foci in the north-eastern part of the country. This report describes for the first time a case of clinical TBE in a roe deer, occurred in the Belluno province, Veneto region, an area highly endemic for the presence of the virus. The affected roe deer showed ataxia, staggering movements, muscle tremors and persistent teeth grinding causing hypersalivation. At necropsy, the macroscopic picture was inconclusive. RNA of TBEV was detected by real-time RT-PCR. Phylogenetic analysis revealed a close relationship to TBEV of the European subtype, and 100% similarity with a virus from the bordering Trento Province. The histological examination of the midbrain confirmed the viral etiology and specific immunofluorescence indicated the presence of a Flavivirus infection and characterized the pattern of infection in the neurons. This report underlines for the first time the occurrence of clinical encephalitic manifestations due to TBEV in a roe deer, thussuggesting to include this pathogen in the frame of differential diagnosis in this species.

The ability to directly look into genome sequences has opened great opportunities in plant breeding. Yet, the assembly of full-length chromosomes remains one of the most difficult problems in modern genomics. Genetic maps are commonly used in de novo genome assembly and are constructed on the basis of a statistical analysis of the number of recombination rather than physical distance in base pairs. This may affect the accuracy of the ordering and orientation of scaffolds within the chromosome, especially in the region of recombination suppression. Here we report the use of Tyr-FISH for validation of genetic and pseudochromosome maps. For probe design we developed a pipeline that is based on selection of a unique sequence with minimal potential fluorescent background arising from non-specific in situ hybridization. In total of 24 unique genes were located on physical chromosomes 2 and 6. The order of markers has been corrected by integration genetic and cytogenetic maps. Tyr-FISH mapping showed that the order of 23.1% (chromosome 2) and 27.3% (chromosome 6) of the tested genes differed between physical chromosomes and pseudochromosomes. Also the position of the mlh1 gene, which was not on the genetic map, was defined on physical chromosome 2. The results suggest the possibility of Tyr-FISH mapping of any gene that may not be neither on the genetic map nor in the assembly. Hence, Tyr-FISH provides valuable information for the improvement of the genome assembly.

Recent studies indicated that Plasmodium vivax can infect Duffy-negative individuals, but the varied diagnostic and methodological approaches have limited our ability to characterize P. vivax across Africa. Here, we utilized a standardized approach to compare epidemiological and genetic attributes of P. vivax from Botswana, Ethiopia, and Sudan, where Duffy-positive and Duffy-negative individuals coexist. Among 1,215 febrile patients, the proportions of Duffy negativity range from 20-36% in East Africa to 84% in Southern Africa. Considerable differences were observed in P. vivax prevalence among Duffy-negative populations ranging from averaged 9.2% in Sudan to 86% in Botswana. P. vivax parasite density in Duffy-negative infections is significantly lower than in Duffy-positive infections. Phylogenetic analyses of 229 PvDBP sequences indicated that Duffy-negative P. vivax were not monophyletic but occurred in multiple well-supported clades, suggesting independent origins. Duffy-negative Africans are clearly not resistant to P. vivax and the public health significance should no longer be neglected.

Bus operators around the world are facing the transformation of their fleets from fossil-fuelled to electric buses. Two technologies prevail: Depot charging and opportunity charging at terminal stops. Total cost of ownership (TCO) is an important metric for the decision between the two technologies, however, most TCO studies for electric bus systems rely on generalised route data and simplifying assumptions that may not reflect local conditions. In particular, the need to re-schedule vehicle operations to satisfy electric buses’ range and charging time constraints is commonly disregarded. We present a simulation tool based on discrete-event simulation to determine the vehicle, charging infrastructure, energy and staff demand required to electrify real-world bus networks. These results are then passed to a TCO model. A greedy scheduling algorithm is developed to plan vehicle schedules suitable for electric buses. Scheduling and simulation are coupled with a genetic algorithm to determine cost-optimised charging locations for opportunity charging. A case study is carried out in which we analyse the electrification of a metropolitan bus network consisting of 39 lines with 4748 passenger trips per day. The results generally favour opportunity charging over depot charging in terms of TCO, however, under some circumstances, the technologies are on par. This emphasises the need for detailed analysis of the local bus network in order to make an informed procurement decision.

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

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.

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

Densimetric Froude (Fr) is the minimum velocity required to prevent sediment deposition in pipes. Prediction of Fr is of utmost importance in numerous applications in civil engineering. In this paper through using a new hybrid method. Genetic Algorithm (GA) is used for optimum selection of membership functions of Adaptive Neuro-Fuzzy Inference System (ANFIS), and Singular Value Decomposition (SVD) method is used to compute the linear parameters of ANFIS’s results section (ANFIS-GA/SVD). Also, two different target functions are known as training error (TE) and prediction error (PE) by Pareto curve, the trade-off between these functions is selected as the optimal modeling point. First, different models will be presented using the parameters affecting Fr prediction, classifying them in different groups; then the Fr parameter will be predicted for all the different models through utilizing three different sets of data and the ANFIS-GA/SVD technique. The results of the models indicate that the best Fr prediction is obtained when independent parameters such as volumetric sediment concentration (CV), ratio of median diameter of particle size to pipe diameter (d/D), ratio of median diameter of particle size to hydraulic radius (d/R) and overall friction factor of sediment (λs) use as input variables in prediction of Fr. A sensitivity analysis is also conducted for the purpose of examining the effect of each of the dimensionless parameters on Fr prediction accuracy. Comparing the results of the suggested models with the existing regression-based equations shows that ANFIS-GA/SVD (R²=0.986, MAPE=4.397, RMSE=0.206, SI=0.053, ρ=0.026, BIAS=-0.025) is more accurate than the rest of the models.

leaf beetle (BLB) (Ootheca mutabilis) has emerged as an important bean pest in Uganda, leading to devastating crop losses. There is limited information on the population genetic structure of BLB despite their importance. In this study, novel microsatellite markers and the partial mitochondrial cytochrome oxidase subunit I (mtCOI) gene sequences were used to analyze the spatial population genetic structure, genetic differentiation, gene flow and haplotype diversity of 87 O. mutabilis samples from five populations. We identified 19,356 simple sequence repeats (SSRs) (mono, di, tri, tetra, penta, and hexa-nucleotides) of which 81 di, tri and tetra-nucleotides were selected for primer synthesis. Five highly polymorphic SSR markers (4-21 alleles, heterozygosi-ty 0.59-0.84, polymorphic information content (PIC) 50.13-83.14%) were used for this study. Analyses of the five O. mutabilis populations with these five novel SSRs found 89% of genetic variation occurring within individuals, 9% among individuals and 2% among populations. Genetic differentiation was low but significant for SSR and insignificant for mtCOI partial sequence data while gene flow was high across the populations. There was no evidence of isolation by distance between geographical and genetic distances. Bayesian clustering identified signature of admixture that suggests genetic contributions from two ancestral genetic lineages, and the median-joining haplotype network showed low differentiation of many different haplotypes from the most common haplotype. Low genetic differentiation and high gene flow indicates unrestricted migrations between populations. This information will contribute to the design of BLB control strategies.

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.

Lightning discharges in electric power networks generate voltage and current surges that are propagated through the electrical network causing damage and shutdowns in the electrical system. To protect the system against these phenomena, surge arresters are very effective and widely used by electrical utilities in their electric grids. This paper presents a methodology for optimized surge arrester allocation based on genetic algorithm (GA), creating a simulation environment in the software ATP (Alternative Transients Program) to implement the proposed methodology. The optimized allocation procedure is based on a fitness function that minimizes the cost of surge arresters and maximizes the number of protected equipment. To carry out this optimized arrester allocation procedure using ATP may demand too much processing time when running large distribution grids. To overcome this difficulty a procedure is proposed to obtain an overvoltage severity description of the grid and select the most critical electric nodes for the incidence of lightning discharges, in the GA allocation procedure. The case study is applied to the IEEE 123-bus electrical feeder to demonstrate the effectiveness of the proposed methodology.