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

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.

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.

The gene translation system possesses inherent complexity in distinguishing codons with degeneracy through repertoires of aminoacyl-tRNAs in the ribosome. Implementation of inosine nucleoside at the anticodon wobble-position in certain tRNAs, especially in eukaryotes, might be arisen to establish complex decoding systems. This report introduces the novel concept of “decoding tables”, which serve as concise summaries of codon-anticodon pairings provided in codon table-like format. Utilizing tRNA genome database information and a procedure based on compiled tRNA studies, the tRNA repertoire and the use of wobble pairings can be depicted for any organisms. The decoding table sheds light on the use of wobble pairings across diverse organisms.

RBF networks are used in a variety of real-world applications such as medical data or signal processing problems. The success of these parametric models lies in the successful adaptation of their parameters using efficient computational techniques. In the current work, a method of adjusting the parameters of these networks using Grammatical Evolution is presented. Grammatical Evolution will be used to successfully discover the most promising range of parameter values and then the training of the parameter set will be achieved using a Genetic Algorithm. The new method was applied to a wide range of data fitting and classification problems, and the results were more than promising.

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.

Seed germination and seedling growth represent two vulnerable stages in a plant life cycle and it is important to determine how they will be affected by environmental changes associated with climate change. This study examines the impact of salinity levels (0, 50, 100, and 150 mM) at each of three temperatures (15, 25, and 35˚C) on seed germination and radicle growth for three dormant and three non-dormant varieties of conventional, glyphosate resistant, or reduced lignin alfalfa. The genetic basis and phenotypic plasticity for seed germination and seedling growth in response to salinity and temperature were determined. Both traits were phenotypically plastic with respect to temperature and salinity. Seed germination was 87.0% ± 1.7 at 25˚C, 0mM (no salinity), but decreased to 33.9% ± 3.9 germination at 35˚C and 150mM. Radicle length went from 36.7 ± 1.5 mm after four days at 25˚C, 0mM, to 10.5 ± 0.7 mm at 35˚C, 150mM. The phenotypic response brought seed germination and radicle length away from their optimum, but we detected standing genetic variation for both seed germination and radicle length. Selection to increase both traits at high temperature and salinity would facilitate alfalfa establishment under climate change.

This article discusses how, in today’s world of disruptive and dramatic social change (DSC), non-sports related coaching, which includes a wide range of services such as life coaching, career coaching, executive coaching, and team coaching, can inadvertently fuel undesirable social dynamics. There is little or no awareness of this risk among coaches and coachees. The global, fast-growing, multi-billion-dollar industry aimed at supporting people and organisations to perform better and increase wellbeing while managing and adapting to change has been developed with limited sociological input. The article is based on 15 years of social constructionist-informed reflective practice by a sociologist-turned-coach, and uses a multi-layered autoethnographic account to argue for a sociologically informed paradigm shift in coaching, as well as relevant sociological knowledge and social and human sciences research methodology in coaches’ education. It presents the rationale and key features of a new coaching approach that places DSC-relevant sociological concepts at the heart of the coaching process, helps people develop psycho-sociological awareness, and uses a learning-to-develop through research design. A new definition of coaching to address DSC is derived. Coaching practitioners will find DSC-relevant sociological concepts, critical reflections, coaching questions, and procedures to expand coaching effectiveness. Interdisciplinary research topics combining coaching sociology and coaching psychology are suggested.

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

Guava (Psidium guajava L.) is a species is widely distributed in Córdoba, despite this, there are few studies that have been carried out to understand its genetic diversity. For this reason, the objective of this research was to evaluate the genetic diversity and variability of guava (Psidium guajava L) using microsatellite markers in Montería, Córdoba-Colombia. Forty-five accessions were evaluated. For DNA extraction, the CTAB 2x extraction protocol was used with modifications. The extracted DNA was amplified by the PCR technique using seven microsatellite markers. A total of 46 alleles were found with an average of 6.5 alleles per locus. A total of 28 private alleles were identified in the populations, possibly fixed by different evolutionary forces. The evaluated population presented an average expected heterozygosity of 0.572 and the observed heterozygosity was lower (0.058). The fixation index presented a total average of 0.906, indicating that in Montería there is an excess of homozygotes. The PIC values allowed us to determine that the markers mPgCIR9, mPgCIR11, mPgCIR13, mPgCIR16, mPgCIR19 and mPgCIR22 are highly informative, while mPgCIR23 is moderately informative. The guava population in Montería presented a low genetic diversity within the subpopulations, which could be related to inbreeding events such as self-pollination..

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

This study aimed to exploring the intra-species distribution of genetic characters that favor the persistence in the gastrointestinal tract (GIT) and host interaction of bacteria belonging to the species Lacticaseibacillus genus. These bacterial species comprise commercial probiotics with the widest use among consumers and strains naturally occurring in GIT and in fermented food. Since little is known on the distribution of genetic traits for adhesion capacity, polysaccharide production, biofilm formation, utilization of substrates critically important for survival in GIT, that influence probiotic characteristics, a list of genetic determinants involved in such functions was created by a search for specific genes involved in the above aspects in the genome the extensively characterized probiotic L. rhamnosus GG. The presence/absence and variability of each gene in other Lacticaseibacillus spp. genomes was assessed by alignment with the publicly available fully annotated genome sequences. Eighty-two gene loci were compared, and 49 of these were found to be absent in some genomes in a species or strain-specific mode. A set of genes was found to be conserved, indicating that all strains of the genus may exert some probiotic effects. Among the variable loci a taurine utilization operon and a α-L-fucosidase were examined for presence/absence in 26 strains isolated from infant feces by PCR based tests. Results were variable among the isolates, though their common origin indicated the capacity to survive in the intestinal niche. This study indicated that the capacity to exert probiotic actions of Lacticaseibacillus spp. depends on a conserved set of genes and is enhanced by variable genetic factors whose role is only in part elucidated. The selection of strains of the most promising probiotic candidates to be used in food is feasible by analyzing presence/absence of a set of variable traits.

Studies on the domestication, genetic differentiation, and crop evolution of foxtail millet are re-viewed. Several genetic studies were carried out to elucidate the genetic relationships among foxtail millet accessions originating mainly from Eurasia, based on intraspecific hybrid pollen semi-sterility, isozymes, DNA markers, and single-nucleotide polymorphisms. Most studies suggest that China is the center of diversity of foxtail millet, and landraces were categorized into geographical groups. Furthermore, the evolution of genes was reviewed (i.e., the Waxy gene conferring amylose content in the endosperm, the Si7PPO gene controlling polyphenol oxidase, the HD1 and SiPRR37 genes controlling heading time, the Sh1 and SvLes1 genes involved in grain shattering, and the C gene controlling leaf sheath pigmentation), and the variation and distribu-tion of these genes suggested complex patterns of evolution under human and/or natural selec-tion.

Software-Defined Networking (SDN) is a network implementation paradigm of great importance, as it has a profound impact on the pace of technological progress. While SDN doesn’t directly address the technical complexities of routing, congestion control, traffic engineering, security, mobility, reliability, or real-time communication, it paves the way for innovative solutions to emerge for these and similar challenges. Security is of utmost importance in SDN with Distributed Denial of Service (DDoS) being an attack which creates large scale problems. DDoS creates malicious traffic that resembles normal traffic in order to create service problems. As such, mechanisms that distinguish between benign and malicious traffic is essential, since this is the first step to mitigate the problem of DDoS. In this paper, we take a dataset onboard which exhibits benign and malicious traffic in SDN. There are 23 features that are used for classification purposes. Here we utilise classification procedure based on three methods based Grammatical Evolution applied on the aforementioned data. We provide results that show the efficiency of our approach and show that all three methods exhibits satisfactory results.

Artificial neural networks are widely established models of computational intelligence that have been tested for effectiveness in a variety of real-world applications. These models require fitting a set of parameters through the use of some optimization technique. However, an issue that researchers often face is finding an efficient range of values for the parameters of the artificial neural network. This paper proposes an innovative technique of generating a promising range of values for the parameters of the artificial neural network. Finding the value field is done by a series of rules for partitioning the original set of values or expanding it, which rules are generated using Grammatical Evolution. After finding a promising interval of values, any optimization technique such as a genetic algorithm can be used to train the artificial neural network on that interval of values. The new technique was tested on a wide range of problems from the relevant literature and the results were extremely promising.

In the last century, statistical process control has been considered a successful methodology for monitoring the variability and stability of a process over time. The analysis of variability using functional data analysis has become widespread during the early years of the 21st century. The present study proposes the implementation of a hybrid methodology called functional process control based on the functional data analysis methodology and combines its advantages with those of statistical process control, in order to provide a tool for detecting functional deviations. The phases are: (1) stabilization of processes through the identification and elimination of special causes of functional variability; (2) improvement of the process to be controlled by minimizing the common causes of functional variability; and (3) monitoring of the processes to ensure the maintenance or addition of further improvements.

Rice (Oryza sativa L.) is primary dietary source for half of the global population that comprising both essential nutrients and toxic heavy metal elements for human health. A number of nutrients are required within the diet and generally lacking in human diets, and need to biofortify into the rice grains, such as iron (Fe), zinc (Zn), calcium (Ca), potassium (K), sodium (Na), magnesium (Mg), phosphorus (P), copper (Cu), iodine (I), selenium (Se), and Sulphur (S). Meanwhile, some elements are toxic to human, including arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) which need to be eliminated from the rice grains. This article reviews the aspects of phenotypic variation of grain elemental concentration in the diverse rice genotypes, relationship of environmental conditions and rice grain elemental accumulation, correlation between rice grain elemental content and others agronomic traits, and also genetic basis of grain elemental concentration in rice. All of these aspects are important to develop rice varieties with a balanced elemental nutrients and lower toxic heavy metal elements. Enhancing the concentration of essential mineral elements and reducing the accumulation of toxic elements in the rice grain are important to improve the rice quality for human health in addressing mineral deficiency and toxicity that could be accomplished by using plant breeding, agronomic, and genetic engineering approaches.

Ploidy is a significant type of genetic variation, describing the number of chromosome sets per cell. Ploidy evolves in natural populations, clinical populations, and lab experiments, particularly in fungi. Despite a long history of theoretical work on this topic, predicting how ploidy will evolve has proven difficult, as it is often unclear why one ploidy state outperforms another. Here, we review what is known about contemporary ploidy evolution in diverse fungal species through the lens of population genetics. As with typical genetic variants, ploidy evolution depends on the rate that new ploidy states arise by mutation, natural selection on alternative ploidy states, and random genetic drift. However, ploidy variation also has unique impacts on evolution, with the potential to alter chromosomal stability, the rate and patterns of point mutation, and the nature of selection on all loci in the genome. We discuss how ploidy evolution depends on these general and unique factors and highlight areas where additional experimental evidence is required to comprehensively explain the ploidy transitions observed in the field and the lab.

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.

During the 1970s, Tunisian durum wheat landraces were replaced progressively by modern cultivars. These landraces are nowadays maintained by smallholder farmers in some ecological niches and are threatened gradually by extinction resulting on the narrowing of the genetic diversity. This study aims to investigate patterns of phenotypic variability using twelve quantitative traits in a panel of 189 durum wheat landraces and seven checks, based on farmer’s population name attribution and genetic structure. Our results showed high phenotypic variability among and within landraces and checks for the majority of the studied traits. The principal components analysis showed similar grouping using farmers name attribution and genetic structure using K = 6, which confirmed the identification of a new gene pool in the oases of Tunisia, represented by the sub-population Jenah Zarzoura and the robustness and high relationships between phenotypic and genome-wide genetic structure using DArTseq method. These findings will enhance the conservation efforts of these landraces and their use in breeding efforts at national and international levels to adapt to dry conditions.

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.

A surprising insight from the advent of genomic sequencing was that many genes are deeply conserved during evolution. With a particular focus on genes that interact with light in animals, I explore the metaphor of genetic toolkits, which can be operationalized as lists of genes involved in a trait of interest. A fascinating observation is that genes of a toolkit are often used again and again during convergent evolution, sometimes across vast phylogenetic distances. Such a pattern in the evolution of toolkits requires three different stages: origin, maintenance, and redeployment of the genes. The functional origins of toolkit genes might often be rooted in interactions with external environments. The origins of light interacting genes in particular may be tied to ancient responses to photo-oxidative stress, inspiring questions about the extent to which the evolution of other toolkits were also impacted by stress. Maintenance of genetic toolkits over long evolutionary timescales requires gene multifunctionality to prevent gene loss when a trait of interest is absent. Finally, the deployment of toolkit genes in convergently evolved traits like eyes sometimes involves the repeated use of similar, ancient genes but other times involves different genes specific to each convergent origin. How often a particular gene family is used time and again for the same function may depend on how many possible biological solutions are available. When few solutions exist and are maintained, evolution is constrained to use the same genes over and over. However, when many different solutions are possible, the innovative possibilities of evolution are often on display. Therefore, a focus on genetic toolkits highlights the combination of legacy plus innovation that drives the evolution of biological diversity.

Genetic diversity is the foundation of evolutionary resilience, adaptive potential, and the flourishing vitality of living organisms, serving as the cornerstone for robust ecosystems and the continuous evolution of life on Earth. The landscape of directed evolution, a powerful biotechnological tool inspired by natural evolutionary processes, has undergone a transformative shift propelled by innovative strategies for generating genetic diversity. This shift is fuelled by several factors, encompassing the utilization of advanced toolkits like CRISPR-Cas and base editors, enhanced comprehension of biological mechanisms, cost-effective custom oligo pool synthesis, and the seamless integration of artificial intelligence and automation. This comprehensive review looks into the myriad methodologies employed for constructing gene libraries, both in vitro and in vivo, categorized into three major classes: random mutagenesis, focused mutagenesis, and DNA recombination. The objectives of this review are threefold: firstly, to present a panoramic overview of recent advances in genetic diversity creation, secondly, to inspire novel ideas for further innovation in the genetic diversity generation, and thirdly, to provide a valuable resource for individuals entering the field of directed evolution.

With improved measurement and modelling technology, variability has emerged as an essential feature in non-equilibrium processes. While traditionally, mean values and variance have been heavily used, they are not appropriate in describing extreme events where a significant deviation from mean values often occurs. Furthermore, stationary Probability Density Functions (PDFs) miss crucial information about the dynamics associated with variability. It is thus critical to go beyond a traditional approach and deal with time-dependent PDFs. Here, we consider atmospheric data from the Whole Atmosphere Community Climate Model (WACCM) and calculate time-dependent PDFs and the information length from these PDFs, which is the total number of statistically different states that a system passes through in time. Time-dependent PDFs are shown to be non-Gaussian in general, and the information length calculated from these PDFs shed us a new perspective of understanding variabilities, correlation among different variables and regions. Specifically, we calculate time-dependent PDFs and information length and show that the information length tends to increase with the altitude albeit in a complex form. This tendency is more robust for flows/shears than temperature. Also, much similarity among flows and shears in the information length is found in comparison with the temperature. This means a stronger correlation among flows/shears because of a strong coupling through gravity waves in this particular WACCM model. We also find the increase of the information length with the latitude and interesting hemispheric asymmetry for flows/shears/temperature, a stronger anti-correlation (correlation) between flows/shears and temperature at a higher (low) latitude. These results also suggest the importance of high latitude/altitude in the information budge in the Earth's atmosphere, the spatial gradient of the information as a useful proxy for the transport of physical quantities.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

The European Fish Index EFI+ is the only fish-based multimetric index for the assessment of the ecological status of running waters validated and thus applicable across the European Union. Metrics of the index rely on several attributes of the species present in the fish assemblage, irrespective of their native/alien status. The abundance of alien fish, together with other anthropogenic impacts, is one of the most important threats to the conservation of native fish and ecosystem health and is also an indicator of degraded stream conditions. Therefore, to improve the performance and utility of the EFI+ in regions with high incidence of alien species, the EFI+ was adapted to include the alien fish pressure by averaging the two original metrics with a new metric that reflects the number of alien species as well as the proportional abundance of alien individuals. The application of the adapted index (A-EFI+) is illustrated with data from several Iberian Mediterranean basins and showed similar or stronger correlations than the original EFI+ with anthropogenic pressure (land-use variables) and with other regional fish indices. EFI+ has been invaluable to intercalibrate fish indices across Europe and A-EFI+ is similar but explicitly includes the alien pressure, thus helping to provide a more comprehensive assessment of ecosystem health and to communicate it to society.

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate set by the level of standing allelic diversity in a population. The process of speciation is driven by a combination of two evolutionary forces: genetic drift and ecological selection. Genetic drift takes place under conditions of relaxed selection, and results in a balance between rates of mutation and rates of genetic substitution. These two processes, drift and selection, are necessarily mediated by a variety of mechanisms guaranteeing genome stability in any given species. One of the outstanding questions in evolutionary biology concerns the origin of the widely varying phylogenetic distribution of biodiversity across the tree of life, and how the forces of drift and selection contribute to shaping that distribution. The following examines some of the molecular mechanisms underlying genome stability and the adaptive radiations that are associated with biodiversity and the widely varying species richness and evenness in the different eukaryotic lineages.

The physics–biology continuum relies on the fact that life emerged from prebiotic molecules. Here, I argue that life emerged from the physical coupling between the synthesis of nucleic acids and the synthesis of amino acid polymers. Owing to this physical coupling, amino acid polymers (or proto-phenotypes) maintained the physicochemical parameter equilibria (proto-homeostasis) in the immediate environment of their encoding nucleic acids (or proto-genomes). This protected the proto-genome physicochemical integrity (i.e., atomic composition) from environmental physicochemical stresses, and therefore increased the probability of reproducing the proto-genome without variation. From there, genomes evolved depending on the biological activities they generated in response to environmental fluctuations. Thus, a genome generating an internal environment whose physicochemical parameters guarantee homeostasis and genome integrity has a higher probability to be reproduced without variation and therefore to reproduce the same phenotype in offspring. Otherwise, the genome is modified by the imbalances of the internal physicochemical parameters it generates, until new emerging biological activities maintain homeostasis. In sum, evolution depends on feedforward and feedback loops between genome and phenotype, since the internal physicochemical conditions that a genome generates in response to environmental fluctuations in turn either guarantee the stability or direct the variation of the genome.

A novel coronavirus COVID-19 was first emerged in Wuhan city of Hubei Province in China in December 2019. The COVID-19, since then spreads to 213 countries and territories, and has become a pandemic. Genomic analyses have indicated that the virus, popularly named as corona, originated through a natural process and is probably not a purposefully manipulated laboratory construct. However, currently available data are not sufficient to precisely conclude the origin of this fearsome virus. Genome-wide annotation of thousands of genomes revealed that more than 1,407 nucleotide mutations and 722 amino acids replacements occurred at different positions of the SARS-CoV-2. The spike (S) glycoprotein of SARS-CoV-2 possesses a functional polybasic (furin) cleavage site at the S1-S2 boundary through the insertion of 12 nucleotides. It leads to the predicted acquisition of 3-O-linked glycan around the cleavage site. Although real-time RT-PCR methods targeting specific gene(s) have widely been used to diagnose the COVID-19 patients, however, recently developed more convenient, rapid, and specific diagnostic tools targeting IgM/IgG or newly developed plug and play methods should be available for resource-poor developing countries. Some drugs, vaccines and therapies have shown great promise in early trials, however, these candidates of preventive or therapeutic agents have to pass a long path of trials before being released for the practical application against COVID-19. This review updates current knowledge on origin, genomic evolution, development of the diagnostic tools and the preventive or therapeutic remedies of the COVID-19, and discusses on scopes for further research and effective management and surveillance of COVID-19.

Circular RNAs (circRNAs) served as covalently closed single-stranded RNAs have been proposed to influence plant development and stress resistance. Grapevine is the most economically valuable fruit crops cultivated worldwide and threaten by various abiotic stresses. Herein, we reported that a circRNA (Vv-circPTCD1) processed from the second exon of a pentatricopeptide repeat family gene PTCD1 was preferentially expressed in leaves and responded to salt and drought but not heat stress in grapevine. Additionally, the second exon sequence of PTCD1 was highly conserved but the biogenesis of Vv-circPTCD1 is species-dependent in plants. It was further found that the overexpressed Vv-circPTCD1 can slightly decreased abundance of the cognate host gene and the neighboring genes were barely affected in grapevine callus. Furthermore, we also successfully overexpressed the Vv-circPTCD1, and found that the Vv-circPTCD1 deteriorated the growth during heat, salt, and drought stresses in Arabidopsis. However, the biological effects on grapevine callus were not always consistent with that of Arabidopsis. Interestingly, we found that the transgenic plants of linear counterpart sequence also conferred the same phenotypes as that of circRNA during the three stress conditions, no matter what species. Those results imply that although the sequences are conserved, the biogenesis and functions of Vv-circPTCD1 are species-dependent. Our results indicate that the plant circRNA function investigation should be conducted in homologous species, which support valuable reference for further plant circRNA studies.

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.

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: 1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)], and 2) of bases in form of codons 3) direct – complement like codon/anticodon symmetry in the sixteen alternating boxes of the genetic code columns, 4) A+T rich and C+G rich alternate codons in the same row between both columns of the genetic code, 5) the same position between divided and undivided codon boxes in relation to horizontal mirror symmetry axes. The SSyGC table has a unique physicochemical purine – pyrimidine symmetry net which is as the core symmetry common for all, more than thirty different nuclear and mitochondrial genetic codes. This net is present in the SSyGC table of all RNA and DNA living species. None of these symmetries is present in the Standard Genetic Code (SGC) table which is constructed on the alphabetic horizontal and vertical U-C-A-G order of bases. Here we show that the free energy value of each codon incorporated as fundamentally mapping the “energy code” in the SSyGC table is compatible with mirror symmetry. On the other hand, in the SGC table the same free energy values of codons are dispersed and a mirror symmetry between them is not recognizable. At the same time the mirror symmetry of the SSyGC table and the DNA quadruplets together with our classification of codons/trinucleotides are perfectly imbedded in the mirror symmetry energy mapping of codons/trinucleotides and point out in favor of maintaining the integrity of the genetic code and DNA genome. We also argue that physicochemical symmetries of the SSyGC table in the manner of the purine – pyrimidine symmetry net, the quadruplet symmetry of DNA molecule and the free energy of codons have remined unchanged during all of evolution. The unchangeable and universal symmetry properties of the genetic code, DNA molecule and energy code are decreasing disorder between codons/trinucleotides and shed a new light on evolution. Diversity in all living species on Earth is broad, but the symmetries of the Supersymmetry Genetic Code as the code of life and the DNA quadruplets related to the” energy code” are unique, unchangeable and have the power of natural laws.

Bottom-up synthesis of porous NiMo alloy reduced by NiMoO₄ nanofibers was systematically investigated to fabricate non-noble metal porous electrodes for hydrogen production. The different annealing temperatures of NiMoO₄ nanofibers under hydrogen atmosphere reveal that the 950 °C annealing temperature is a key to produce bicontinuous porous NiMo alloy without oxide phases. The porous NiMo alloy as cathodes in electrical water splitting demonstrates not only almost identical catalytic activity with commercial Pt/C in 1.0 M KOH solution, but also superb stability for 12 days at an electrode potential of −200 mV (v.s. RHE).

The notion that there is a one to one mapping from genotype to phenotype was overturned a long time ago. Along with genotype and environment, ‘non-genetic changes’ orchestrated by altered RNA and protein molecules also guide the development of phenotype. The idea that there is a route through which changes in phenotype can lead to changes in genotype impinges on several phenomena of molecular, developmental, evolutionary and applied interest. Phenotypic changes that do not alter the underlying DNA sequence have been studied across model systems (eg: DNA and histone modifications, RNA editing, prion formation) and are known to play an important role in short term adaptation. However, because of their transient nature and unstable inheritance, the role of such changes in long term evolution has remained controversial. I classify and review three ways in which non-genetic changes can influence genotype and impact cellular fitness across generations, with an emphasis on the enticing idea that they may act as stepping stones for genetic adaptation. I focus on work from microbial systems and attempt to highlight recent experiments and models that bear on this idea. Overall, I review evidence which suggests that non-genetic changes can impact phenotype via their influence on the genotype, and thus play a role in evolutionary change.

The genetic code evolved by parallel tracks of chaotic and ordered processes. Liquid-liquid phase separation (hydrogels), a chaotic process, constructs diverse membraneless compartments within cells, resulting in regulated hydration and sequestration and concentration of reaction components. Hydrogels relate to chaotic amyloid fiber production. We propose that polyglycine and related hydrogels (i.e. GADV; G is glycine), phase separations, membraneless droplets and amyloid accretions organized protocell domains to drive the earliest evolution of the genetic code and the pre-life to cellular life transition. By contrast, evolution of tRNA, tRNAomes, aminoacyl-tRNA synthetases and translation systems followed highly ordered and systematic pathways, described by well-defined mechanisms and rules. The pathway of evolution of aminoacyl-tRNA synthetases, which tracked evolution of the genetic code, is clarified. Hydrogels and amyloids form a chaotic component, therefore, that complemented otherwise systematic processes. We describe with detail a pre-life world in which hydrogels and amyloids provided the selections of the first life.

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

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

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.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

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.

The burdens of malnutrition, protein and micronutrient deficiency, and obesity cause enormous costs to society. Crop nutritional quality has been compromised by the emphasis on edible yield and through the loss of biodiversity due to the introduction of high-yielding uniform cultivars. Heirloom crop cultivars are traditional cultivars grown for a long time (> 50 years), and whose heritage has been preserved by regional, ethnic or family groups. Heirlooms are recognized for their unique appearance, names, uses and historical significance. They are gaining in popularity because of their unique flavors and cultural significance to local cuisine, and their role in sustainable food production for small-scale farmers. As a contrast to modern cultivars, heirlooms may offer a welcome alternative in certain markets. Recently, market channels have emerged for heirloom cultivars in the form of farmer-breeder-chef collaborations and seed savers organizations. There is therefore urgent need to know more about the traits available in heirloom cultivars, particularly for productivity, stress tolerance, proximate composition, sensory quality and flavor. This information is scattered and the intention of this review is to document some of the unique characteristics of heirloom cultivars that may be channeled into breeding programs for developing locally adapted high value cultivars.

The major histocompatibility complex (MHC) genes are the most polymorphic genes in vertebrates, and their proteins play a critical role in adaptive immunity for defense against a variety of pathogens. MHC diversity was lost in many species after experiencing a decline in size. To understand the variation and evolution of MHC genes in the Siberian ibex, Capra sibirica, which has undergone a population decline, we analyzed the variation of the second exon of MHC class II DRB genes in samples collected from five geographic localities in Xinjiang, China, that belong to three diverged mitochondrial clades. Consequently, we identified a total of 26 putative functional alleles (PFAs) with 260 bp in length from 43 individuals, and found one (for 27 individuals) to three (for 5 individuals) PFAs per individual, indicating the presence of one or two DRB loci per haploid genome. The Casi-DRB1*16 was the most frequently occurring PFA, Casi-DRB1*22 came after found in only seven individuals, 14 PFAs occurred once (7 PFAs twice), implying high frequency of rare PFAs. Interestingly, more than half of the (15) PFAs were specific to clade I, only one and three PFAs were specific to clades II and III, respectively. So, we assume that the polygamy and sextual segregation nature of this species likely contributed to the allelic diversity of DRB genes. Genetic diversity indices showed that PFAs of clade II were lower in nucleotide, amino acid, and supertype diversity compared to those of the other two clades. The way of allele sharing and FST values between three clades were to some extent in agreement with pattern observed in mitochondrial DNA divergence. In addition, recombination analyses revealed no evidence for significant signatures of recombination events. Alleles shared by clades III and the other two clades diverged 6 million years ago, and systematic neighbor grids showed cross-species polymorphisms. Together with the PAML and MEME analyses, the results indicated that the DRB gene in C. sibirica evolved under balancing and positive selection. However, by comparison, it can be clearly seen that different populations were under different selective pressures. Our results are valuable in understanding the diversity and evolution of the DRB gene in a mountain living C. sibirica and in making decisions on future long-term protection strategies.

Microbial immune escape represents the primary cause of induced pathogenesis in humans, and it represents a pivotal method used by viral agents to increase their load and suppress key mechanisms of the innate and adaptive immune system. This phenomenon represents the primary factor that led to the onset of the 1918-1920 A(H1N1) Influenza and 2020-2022 COVID-19 pandemics, and it possibly played a major role in the onset of the AIDS pandemic as well. Moreover, repeated incidents of immune evasion could be associated with higher rates of cellular aging (Jackson et al., 2017), most likely due to the consequent increased demands of energy consumption. Highly developed viral immune evasion ultimately indicates the high inner intelligence of human immunity due to reflective and imitative characteristics of reactions that are produced against initial actions. Ribonucleic acid-based viral genomes contain open reading frames, which consist of genes producing sixteen non-structural proteins. Such proteins play a considerable role in desensitizing first-line immunity during cellular infection, and non-structural proteins 1, 10 and 16 have the strongest effects against a healthy expression rate of Type I and Type III Interferon-encoding genes. Type I Interferons consist of IFN-alpha, -beta, -delta, -epsilon, -omega, -tau and -zeta, whilst Type III Interferons consist of IFN-lambda1, -lambda2 and -lambda3, and they act as stimulators of intracellular signalling cascades that in turn lead to the activation and expression of interferon-stimulated genes (Brown et al., 2022). The earlier the interferon-stimulated genes are activated, the lower the extent of pro-inflammatory mediation and overall, the more effective the antiviral immune response will be, given the exponential nature of the viral load increase. Non-structural protein 16 methylates the 5’ cap of the virus, making the pathogen-associated molecular patterns less recognisable by pattern-recognition receptors, and it requires activation by bonding with non-structural protein 10. It is preserved in the S-Adenosyl-L-Methionine pocket of the SARS-CoV-2 genome. Non-structural protein 1 (NS1) directly cleaves the host cell mRNA producing Type I and possibly Type III Interferons, thereby preventing a translation process of the immune proteins. NS1 has recently been found to often be packaged into exosomes once secreted by the viral genome in the cytosol, meaning that exocytosis and paracrine signalling to neighbouring cells before their actual infection is possible. As a result, NS1 is highly capable of silencing the first-line immune responses of uninfected neighbouring cells as well, thereby highlighting the need to adjust the focus of therapeutics and vaccinology toward first-line immunity and further indicating its foundational importance in the support for the development of precise and balanced defenses against microbial agents of concern (EL SAFADI et al., 2022).

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

During the last 150 years, the trout-culture industry focused on enhancing trout populations by stocking, in response to the growing anglers’ demand and the habitat degradation associated to the rapid urbanization and hydropower development. The industrialized north of Italy, home to the Italian Alpine and subalpine trout populations, is the source of most of the revenues of the national trout-culture industry. Its rapid growth and the massive introduction of non-native interfertile trouts eroded the genetic diversity of native lineages, leading to harsh confrontations between scientists, institutions, and sportfishing associations. We review here the state of art of the taxonomy and distribution of the northern Italian native trouts, presenting both scientific results and historical documentation. We think the only native trouts in this region are Salmo marmoratus, widespread in this region, plus small and fragmented populations of S. ghigii, present only in the Southwestern Alps. We strongly recommend the interruption of stocking of domesticated interfertile non-native trouts in this area, and recommend the adoption of Evolutionary Significant Units for salmonid fishery management. We further propose future research directions for a sustainable approach to the conservation and ecosystem management of the fishery resources and inland waters of northern Italy.

Suitable measures of grazing impacts on ground cover, that enable separation of the effects of climatic variations, are needed to inform land managers and policy makers across the arid rangelands of the Northern Territory of Australia. This work developed and tested a time-series, change-point detection method for application to time series of vegetation fractional cover derived from Landsat data to identify irregular and episodic ground-cover growth cycles. These cycles were classified to distinguish grazing impacts from that of climate variability. A measure of grazing impact was developed using a multivariate technique to quantify the rate and degree of ground cover change. The method was successful in detecting both long term (> 3 years) and short term (< 3 years) growth cycles. Growth cycle detection was assessed against rainfall surplus measures indicating a relationship with high rainfall periods. Ground cover change associated with grazing impacts was also assessed against field measurements of ground cover indicating a relationship between both field and remotely sensed ground cover. Cause and effects between grazing practices and ground cover resilience can now be explored in isolation to climatic drivers. This is important to the long term balance between ground cover utilisation and overall landscape function and resilience.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

A temperate deep lake, Lake Kuttara, Hokkaido, Japan (148 m deep at maximum) was completely frozen every winter in the 20th century. However, unfrozen conditions of the lake over winter occurred four times in the 21st century, which is probably due to global warming. In order to understand how thermal regime of the lake responds to climate change, its heat storage change was calculated by estimating heat budget of the lake and monitoring water temperature at the deepest point for September 2012–June 2016. As a result, temporal change of the heat storage from the heat budget was very consistent with that from the direct temperature measurement (determination coefficient R² = 0.827). The 1978–2017 data at a meteorological station near Kuttara indicated that there are significant (less than 5% level) long-term trends for air temperature (0.024 °C/yr) and wind speed (−0.010 m/s/yr). A sensitivity analysis for the heat storage from the heat budget estimate and an estimate of return periods for mean air temperature in mid-winter allow us to conclude that the lake could be unfrozen once per about two year in a decade.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

Talker variability has been reported to facilitate generalization and retention of speech learning, but is also shown to place demands on cognitive resources. Our recent study provided evidence that phonetically-irrelevant acoustic variability in single-talker (ST) speech is sufficient to induce equivalent amounts of learning to the use of multiple-talker (MT) training. This study is a follow-up contrasting MT versus ST training with varying degrees of temporal exaggeration to examine how cognitive measures of individual learners may influence the role of input variability in immediate learning and long-term retention. Native Chinese-speaking adults were trained on the English /i/-/ɪ/ contrast. We assessed the trainees’ working memory and selective attention before training. Trained participants showed retention of more native-like cue weighting in both perception and production regardless of talker variability condition. The ST training group showed long-term benefit in word identification, whereas the MT training group did not retain the improvement. The results demonstrate the role of phonetically-irrelevant variability in robust speech learning and modulatory functions of nonlinguistic working memory and selective attention, highlighting the necessity to consider the interaction between input characteristics, task difficulty, and individual differences in cognitive abilities in assessing learning outcomes.

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

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

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

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

African locust bean (Parkia biglobosa (Jacq.) is a multi-purpose economic tree with genetic potentials in sub-Saharan Africa. Its cultivation and production is declining with increased aging and genetically threatened throughout its natural ranges. Research efforts are needed to change the present scenario to sustainable cultivation and utilization, hence this present study. This study was aimed at evaluating genetic diversity and geographical spread relationships of twenty landraces collected from different ecological zones of Nigeria using simple sequence repeat (SSR) markers. Ten SSR markers were screened and five primers (PbL02, PbL03, PbL04, PbL05 and PbL09) were selected based on clear amplification products and reproducible scorable bands. The SSR primers detected a total of 55 alleles ranged from 10 to 14 alleles with a mean of 11. The percentage polymorphisms were high and ranged from 68.75 % in PbL04 to 84.21 % in PbL05 with a mean of 74.16 %. The polymorphic information content (PIC) was in the range of 0.31 in PbL02 to 0.37 in PbL09. The genetic diversity and heterozygosity values ranged from 0.39 to 0.50 and 0.00 to 0.68 while the average genetic distance for all pair wise comparisons was 0.31.The first five Principal Component (PC) accounted for 70.20 % of the total variation out of which PC1 (31.50%) and PC2 (19.20%) extracted 49.70% molecular similarity. The dendrogram resulted in separation of the 19 landraces into three major clusters based on unweighted pair group method with arithmetic average. Cluster I comprised of five landraces: ABNo130 and BENo023; OYNo11, KANo125 and NiNo262 while cluster II had only one (BANo116). Cluster III was diverse comprising 13 landraces: ZANo188, KNNo162, KENo220, GMNo076 and EbNo260, ADNo64, EdNo164, KANo137, KENo217, KwNo270, NiNo241, OsNo206 and PLNo120. The homogeneity of alleles among the studied landraces suggested suspicion of loss of genetic intra-specific variation among the landraces of P. biglobosa which calls for concerted efforts toward better cultivation, conservation, management, utilization and genetic improvement of the species in Nigeria.

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.

Climate change, recognized as a global crisis, is not only altering our environment but also significantly impacting human health. Particularly, its influence on non-communicable diseases (NCDs), a leading cause of global mortality, is becoming increasingly evident yet underexplored. This review aims to synthesize current research on the impact of climate change on NCDs, addressing a critical gap in our understanding of how environmental changes affect human health. We examine the complex interplay between climate change and NCDs, drawing insights from recent studies that highlight the adverse effects of climate variables on chronic diseases, such as cardiovascular and kidney diseases, and the role of food and nutrition security in this nexus. Furthermore, the review explores the disproportionate impact on vulnerable regions and populations, particularly in Pacific Island countries and territories, underscoring the urgent need for context-specific solutions and a cross-sectoral approach. By integrating findings from various disciplines, this review aims to inform policy and public health interventions, highlighting the necessity of collaborative efforts to mitigate the burgeoning burden of NCDs in a rapidly changing climate.

Translation of the genetic code into proteins is the main process across all life and ribosomes are ancient cellular machines uniquely enabling this information transformation. We provide a brief overview of the recent advances in linking the ribosomal structure and evolution. Based on these insights into ribosomal organisation across time, we propose that early replication and protein biosynthesis functions were inseparable and in fact were performed by the same ancient RNA molecule, the riboreplisome. Riboreplisome hypothesis helps to address issues of non-Darwinian evolution and complicated starting point that are characteristic to the RNA world, protein world and RNA:protein mixed co-development theories. We suggest that the riboreplisome is the missing link and a molecular machine connecting chemical and biological evolution paths, by being capable of basic genetic and feature selection functions in a cell- or cell-free setting. The riboreplisome hypothesis allows ease of sequential, genetically uninterrupted emergence and sophistication of the genetic code and its decoding machinery, and provides plausible explanations to the origins of the three main RNA types involved in the decoding: the ribosomal, transfer and messenger RNA. Furthermore, riboreplisome can help explaining the co-evolution of aminoacylation machinery, the driving force behind selective gene transcription and expression, and the cell-like compartmentalisation. While we may never find the original riboreplisome again, we might continue to discover different molecular remnants of its prior existence across the existing biological RNA, which, once identified or resurrected, can be useful in synthetic biology applications.

There are no theorems (proven theories) in the biological sciences. We propose that the 3 31 nt minihelix tRNA evolution theorem be universally accepted as one. The 3 31 nt minihelix theorem completely describes evolution of type I and type II tRNAs from ordered precursors (RNA repeats and inverted repeats). Despite diversification of tRNAome sequences, statistical tests overwhelmingly support the theorem. Furthermore, the theorem relates the dominant pathway for the origin of life on Earth, specifically, how tRNAomes and the genetic code may have coevolved. Alternate models for tRNA evolution (i.e., 2 minihelix, convergent and accretion models) are falsified. In the context of the pre-life world, tRNA was a molecule that via mutation could modify anticodon sequences and teach itself to code. We relate the clearest history to date of the chemical evolution of life on Earth. From analysis of tRNA evolution, ribozyme-mediated RNA ligation was a primary driving force in evolution of complexity during the pre-life to life transition on Earth.

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.

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

Older adults in low-and middle-income countries experience a disproportionate burden of non-communicable diseases (NCDs). Unintentional injuries are among the major NCDs, and falls are the second leading cause of these injuries and deaths worldwide, including in Thailand. We aimed to culturally adapt the CDC’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) for Thai older adults and explore the feasibility, appropriateness, and acceptability of using STEADI in primary care via trained community health workers (CHWs) and care managers (CMs). STEADI takes a coordinated care approach that consists of three steps: screening, assessing, and intervening. In Step a, CHWs screened fall risk in 20 community-dwelling older adults using three key questions and found that all of them had fall risk, then CHWs screened with a Stay Independent questionnaire (range 0-14) and found that 100% have high fall risk (total scores 9.7± 2.4). In Step b, CMs assessed balance, vision, footwear, postural hypotension, medications, and CHWs assessed home hazards. They found that 50% had poor balance, 70% took 4+ medications,75% fell on the walkway, and 70% had no bathroom modifications. In Step c, individual participants received fall prevention interventions to mitigate their specific fall risk factors. CHWs and CMs indicated high acceptability (19.20±.1.31 of 20 total), appropriateness (18.80± 1.79 of 20 total), and feasibility (18.60±1.67 of 20 total) of the Thai-STEADI intervention. Our study showed that the community-based multifactorial Thai-STEADI delivered by CHWs and CMs is feasible and acceptable to prevent falls in older adults with limited access to health care.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

The overwhelming evidence supports the assertion that the climate is undergoing change. Understanding the perception of locals of the magnitude of climate change and its influence on non-timber forest products (NTFPs) challenge at a global scale. Although studies on climate change, value addition, and the multiple uses of NTFPs and their impact on local livelihoods have been conducted, locals' perceptions of these factors have not been fully explored. This study aims to assess various social factors, including education, gender, and religion, and their influence on locals' perceptions of the abovementioned factors. The research focused on five regions where NTFPs are prevalent in Ghana (Western North, Bono, Ahafo, Ashanti, and Eastern regions). To investigate the impact of social factors on local perceptions of climate change, value addition, and the multiple values of NTFPs within rural communities, a total of 732 interviews with a team of interviewers across these five regions in Ghana were carried out. We applied a logistic regression model to assess the social factors and their influencing locals’ perceptions of the mentioned variables. It was revealed that age, gender, education, and occupation did not significantly influence locals' perceptions of climate change. However, religion was found to influence locals' perceptions of climate change. Furthermore, the results demonstrated that gender (P<0.000328) and education (P<0.00426) strongly influenced locals' perceptions of value addition to NTFPs. In contrast, religion and constraints (related to time, finance, and skills) did not significantly influence locals' perceptions. Additionally, it was observed that gender (0.00132), education (0.00692), and religion (8.12e-05) significantly influenced how locals perceive and use NTFPs. In conclusion, this study provides valuable insights into the intricate interplay among local perceptions, climate change, value addition, multiple uses of NTFPs, and the capacity of NTFPs to enhance the well-being of forest fringe communities. These findings underscore the importance of comprehensive, tailor-made interventions that consider local perspectives and adhere to sustainable approaches, with the aim of optimising the positive impacts of NTFPs in poverty alleviation and overall community development.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

Advances in gene-specific therapeutics for patients with neuromuscular disorders (NMDs) have brought increased attention to the importance of genetic diagnosis. Genetic testing practices vary among adult neuromuscular clinics, with multi-gene panel testing currently being the most common approach; follow-up testing using broad-based methods, such as exome or genome sequencing, is less consistently offered. Here, we use five case examples to illustrate the unique ability of broad-based testing to improve diagnostic yield, resulting in identification of SORD-neuropathy, HADHB-related disease, ATXN2-ALS, MECP2 related progressive gait decline and spasticity, and DNMT1-related cerebellar ataxia, deafness, narcolepsy, and hereditary sensory neuropathy type 1E. We describe in each case the technological advantages that enabled identification of the causal gene, and the resultant clinical and personal implications for the patient, demonstrating the importance of offering exome or genome sequencing to adults with NMDs.

Daily rainfall data was collected for the arid district of Ananthapuramu, Andhra Pradesh state, India from 1981 to 2016 at the sub-district level and aggregated to monthly, annual and seasonal rainfall totals and the number of rainy days. The objective of this study is to evaluate the homogeneity, trend, and trend change points in the rainfall data. After quality checks and homogeneity analysis, a total of 27 rain gauge locations were considered for trend analysis. A serial correlation test was applied to all the time series to identify serially independent series. Non-Parametric Mann-Kendall test and Spearman’s rank correlation tests were applied to serially independent series. The magnitude of the trend was calculated using Sen’s slope method. For the data influenced by serial correlation, various modified versions of Mann-Kendall tests (Pre-Whitening, Trend Free Pre-Whitening, Bias Corrected Pre-Whitening and two variants of Variance Correction Approaches) were applied. A significant increasing summer rainfall trend is observed in 6 out of 27 stations. Significant decreasing trends are observed at two stations in the south-west monsoon season and at two stations in the north-east monsoon season. To identify the trend change-points in the time series, distribution-free Cumulative SUM test and sequential Mann-Kendall tests were applied. Two open-source library packages were developed in R language namely, ‘modifiedmk’ and ‘trendchange’ to implement the statistical tests mentioned in this paper. The study will benefit water resource management, drought mitigation, socio-economic development and sustainable agricultural planning in the region.

Rhododendron is well-known for the colorful corolla. Molecular marker systems have the potentials to elucidate genetic diversity as well as to assess the genetic fidelity in rhododendrons. In the present study, the reverse transcription domains of long terminal repeat retrotransposons were cloned from rhododendrons and used to develop inter-retrotransposon amplified polymorphism (IRAP) marker system. Subsequently, 198 polymorphic loci were generated from the IRAP and inter-simple sequence repeat (ISSR) markers, of which 119 were derived from the IRAP markers. It was justified that in rhododendrons, IRAP markers were superior to the ISSRs in some polymorphic parameters such as the average number of polymorphic loci (14.88 versus 13.17). In comparison with the single one, the combination of IRAPs and ISSRs systems was more discriminative for detecting 46 rhododendron accessions. Further, IRAP markers demonstrated more efficiency in genetic fidelity detection of in vitro R. bailiens, an endangered species just recorded in Guizhzhou Province, China. The available evidences revealed the distinct properties of IRAP and ISSR markers in the rhododendron-associated applications, and highlighted the availability of highly informative ISSR and IRAP markers in the genetic diversity evaluation and the genetic fidelity assessment of rhododendrons, which may facilitate the preservation and genetic breeding in rhododendron plants.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Rift valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an IFN-competent cell line as well as the production of IFN-β did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results unveil a new RVFV virulence marker highlighting the multiple ways of NSs protein to modulate viral infectivity.

Prokaryotic genomes are dynamic tapestries that are strongly influenced by mobile genetic elements (MGEs), including transposons (Tn’s), plasmids, and bacteriophages. Of these, miniature inverted-repeat transposable elements (MITEs) are undoubtedly the least studied MGEs in bacteria and archaea. This review explores the diversity and distribution of MITEs in prokaryotes and describes what is known about their functional roles in the host and involvement in genomic plasticity and evolution.

This paper introduces the implementation of a genetic programming (GP)-based procedure to the automatic design and tuning of process controllers. The proposed approach makes a significant contribution to the field of artificial intelligence (AI) in control engineering. Unlike other controller design methods, the GP-based program handles the entire design in the time domain, including differential operations like derivatives and integrals, without the need for intermediate inverse Laplace transformation. This approach not only simplifies the design process but also ensures that all generated controllers are implementable in physical systems. Furthermore, GP’s functions set includes various mathematical operations beyond basic arithmetic operators, such as trigonometric, exponential, and logarithmic operators. The performance and validity of the resulting controllers generated by the proposed GP-based approach are evaluated by verifying whether the generator can replicate the structure and performance of those produced by traditional controller design methods and, in some cases, achieve even better results. As a result, the GP-based approach presents a promising solution for automating the controller design process and addressing control problems in various engineering applications.

Exome sequencing has been commonly used in rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) to search for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to heritability in complex clinical traits. We have conducted a systematic review to find evidence supporting the use of EP strategies to search for rare variants in genetic studies of complex diseases, to highlight the contribution of rare variation to the genetic structure of multiallelic conditions. After performing the quality assessment of the retrieved records, we selected 19 genetic studies considering EP to demonstrate genetic association. All the studies successfully identified several rare variants, de novo mutations and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach in patients with an early onset of the disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.

This article presents and discusses analytical data on the scientific publication record from 1910 to 2020 on two topics: "climate" and "climate change/global warming/climate emergency". The goal is to visualize how the publication record on these two topics has evolved over time, from different classification perspectives (year, country, source and organization). Three hypotheses are tested using data collected from Web of Science and various graphical representations of the data. It is found that research output related to the Earth’s contemporary changing climate overtook that of general climate research in 2011, and the publication ratio has been expanding in the last decade. There are significant differences in the publication countries and sources between the two topics, and conversely less significant differences in terms of organizations publishing these works. Differentiation factors that affect the level of research output and engagement on the climate challenge include: island versus landlocked nations, specialized versus general scientific journals, academic versus institutional organizations. The future of the publication records is discussed, such as the emergence of new terms to refer to the climate challenge, such as “climate emergency”.

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.

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.

The objective of this study was to identify the factors determining a company’s corporate governance related to climate change. We analyzed the effect of various sustainability corporate governance variables on the disclosure level of climate change governance. These variables included facts such as having a dedicated sustainability executive and board committee, the mediating effect of female representation on the board of directors, number of reporting years according to TCFD, membership in a sustainability index, MSCI ESG rating, the existence of a corporate climate transition plan, a mention of the UN Global Compact and GRI, company location, as well as company size and profitability. By adopting a multi-theoretical framework that included stakeholder theory as well the legitimacy and agency theory, the underlying research study used a sample of 100 of the largest global companies by market capitalization and their reporting for the year 2020. Based on 1,400 observations for fiscal year 2020 and using correlation analysis, univariate and linear multiple regressions, we find a positive association between having a climate transition plan in place, being a leader in sustainability according to MSCI ratings, and being a DJSI constituent and the propensity to disclose information on governance for climate change. In addition, we find a company with a dedicated sustainability executive show an increased tendency to be transparent on climate governance issues. Furthermore, having a company location in a developed country is significantly and positively associated with climate change governance. Surprisingly, gender diversity in the corporate board or having a sustainability board committee did not show any significant correlation between a higher climate change governance level. The same was true for companies being active in either the extractive or non-extractive sector. Companies referring to the Global Reporting Initiative (GRI) or UN Global Compact also did not score higher in climate change governance. Neither did corporate profitability or size play a significant role. Our results are robust to variations and provide valuable insights for researchers, academics, executives, practitioners as well as regulators. As more and more companies are shifting towards a climate change reporting framework, it is of paramount importance that we are able to determine the contributing variables that lead to effective climate change corporate governance. Our results are inconsistent with stakeholder theory and are strongly suggesting that a diversified board and the existence of a sustainability committee that meets often/sufficiently may not necessarily lead to a higher level of transparency/quality regarding climate change. While more research is needed, knowing that a dedicated sustainability executive as well as having a climate plan in place can make a difference in climate change reporting, can be very beneficial to many corporate stakeholders. Given the current urgent climate change situation and the crucial role that corporation play in it, dedicated sustainability positions and committees need to be established. The findings could be useful for managers as well as governmental standards setter and regulators who are interested in improving corporate practices dealing with climate change. This study applies STATA software with various regression models to empirically test the relationship between CG and other variables and corporate climate change reporting.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

Bactrocera dorsalis Hendel is a highly invasive horticultural pest of major economic importance worldwide. In Burkina Faso, it is one of the main insect pests constraining the mango production and export. Understanding the biology and the genetic dynamics of this insect pest provide cru-cial information for the development of effective control measures. The aim of this study was to understand the distribution, diversity and genetic structure of B. dorsalis in Burkina Faso. Male flies were collected transversally in Burkina Faso and analyzed by PCR using 10 microsatellite markers. The results showed an abundance of B. dorsalis varying from 87 to 2986 flies per trap per day in the different sampling sites. Genetic diversity was high in all sites with an average Shan-non's Information Index (I) of 0.72 per site. Gene flow was high between study populations and ranged from 10.62 to 27.53 number of migrants. Bayesian admixture analysis showed no evi-dence of structure while Discriminant Analysis of Principal Components identified three weakly separated clusters in the population of B. dorsalis in Burkina Faso. The results of this study could be used to optimize the effectiveness of current control interventions and to guide the imple-mentation of new, innovative and sustainable strategies.

Background: There is a paucity of evidence on people with thoracic aortic aneurysm and dissection. We aimed to determine the prevalence of genetic variants and associations with phenotypes. Methods: In the current cross-sectional single centre cohort study of consecutive patients who underwent endovascular or open-surgical repair of thoracic aortic aneurysm and dissection, we applied genetic analysis using four-stage Next Generation Sequencing and confirmed findings with Sanger sequencing. We collected personal and family history on comorbidities, clinical examination, anthropometrics, skeletal deformities, joint function ophthalmological measures. Cardiovascular risk- and phenotype scores were calculated. Results: 95 patients were eligible (mean age 54±9 years, 70% males, 56% aortic dissection). One-fifth had a family history of aortic disease, 95% and 54% had a phenotype score of ≤5 and ≤2, respectively. There weren’t significant differences in the distribution of phenotype characteristics according to age, sex, aortic pathology, or performed invasive procedure. Genetic variants were detected in 40% of patients; classic variants comprised 18% of all variants. We observed no significant association with cardiovascular and phenotype score but with higher joint function scores (p=.015). Conclusion: Genetic variants are highly present in clinically-relevant aortic pathologies. Variants appear to play a larger role than previously described. The different variants don’t correlate with specific phenotypes, nor with age, pathology, sex, or family history.

In the present work we present a methodology for teaching the basis of the genetic code through music composition, with the aim to combine science and arts learning. The project was carried out by 155 students, the so-called MARGA Consortium, with ages comprised between 10 and 17 years from different public schools located in the Principality of Asturias, Spain. The different groups generated 8 different music works using a short genetic sequence obtained from the human notch1 gene, receptor of mutations leading to chronic lymphocytic leukemia.

Glaciation and mountain orogeny have generated new ecologic opportunities for plants, favoring an increase in the speciation rate. Moreover, they also act as corridors or barriers for plant lineages and populations. High genetic diversity ensures that species are able to survive and adapt. Gene flow is one of the most important determinants of the genetic diversity and structure of out-crossed species, and it is easily affected by biotic and abiotic factors. The aim of this study was to characterize the genetic diversity and structure of an alpine species, Festuca ovina L., in Xingjiang, China. A total of 100 individuals from 10 populations were analyzed using six amplified fragment length polymorphism (AFLP) primer pairs. A total of 583 clear bands were generated, of which 392 were polymorphic; thus, the percentage of polymorphic bands (PPB) was 67.24%. The total and average genetic diversities were 0.2722 and 0.2006 (0.1686-0.2225), respectively. The unweighted group method with arithmetic mean (UPGMA) tree, principal coordinates analysis (PCoA) and STRUCTURE analyses revealed that these populations or individuals could be clustered into two groups. The analysis of molecular variance analysis (AMOVA) suggested that most of the genetic variance existed within a population, and the genetic differentiation (Fst) among populations was 20.71%. The Shannon differentiation coefficient (G’st) among populations was 0.2350. Limited gene flow (Nm = 0.9571) was detected across all sampling sites. The Fst and Nm presented at different levels under the genetic barriers due to fragmentation. The population genetic diversity was significant relative to environmental factors such as temperature, altitude and precipitation.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.

The most widely distributed bla_CTX-M gene on a global scale is bla_CTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. This study aimed to review and describe the genetic environments of bla_CTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was done through PubMed, and Google Scholars electronic databases, 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of bla_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected associated with the genetic environment of bla_CTX-M-15 in Africa. Seven different genetic patterns were seen in bla_CTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the bla_CTX-M-15 gene while insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of bla_CTX-M-15 by insertion sequences IS26 and IS3. Class 1 integron (Intl1) was most reported to be associated with bla_CTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transfer bla_CTX-M-15 gene. Aminoglycoside modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with bla_CTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1and IncF plasmid in the mobilization and continental dissemination of the bla_CTX-M-15 gene in Africa.

Objetives: Adequate donor-recipient matching is necessary to achieve the best renal function after transplantation. The nephron load received from the donor, which can be reflected in variables such as age, sex and body mass index, may influence the evolution of the graft. Our objetive was develop a combined score according to the donor-recipient pairing in age, sex and body mass index, and assess its influence on the evolution of the renal graft. Materials and methods: Transplant patients between 2013 and 2020 who had at least 1 year of post-transplant follow-up. A ranking of 0 to 2 points was awarded according to the match between donor and recipient for sex, age and body mass index individually, with higher rank to greater mismatch. Subsequently, a Score with value of 0 to 6 points was created with the combined ranking of the indivudual variables, analyzing its influence on the evolution of the graft by multivariate linear regression. Results: 280 patients followed for 4.3 years of median. Worse renal function was observed at the end of follow-up as the range of each variable increased separately, and the Score created, with a worsening of renal function as the combined Score increased in the multivariate analysis: Coefficient B= -2.4 ml/min, p=0.018. Conclusions: An adequate match between donor and recipient in age, sex and body mass index using this combined Score can help achieve better kidney function after transplantation.

Background: Genetic factors are considered important risk factors for the occurrence of osteoarthritis (OA), which has received extensive attention. This study examined the research on the relationship between genetic factors and the pathogenesis of OA from a bibliometric perspective. Methods: We searched Web of Science Core Collection for original and review articles on genetic factors and OA. We used R package “bibliometrix” to perform statistical and visualization analysis of countries, institutions, authors, journals, and keywords. Results: A total of 1,127 articles met the inclusion criteria, with an average citation of 20.41 per article. From 2012 to 2022, the average annual growth rate of research in this field was 7.83%. The corresponding authors of the published articles were mainly from China, the USA, and the UK. Boston University emerged as the most active and important institution, while the Osteoarthritis and Cartilage published the most articles in this field. The keywords “polymorphism”, “genetic” and “mendelian randomization” indicate the future research directions. Conclusion: This bibliometric study provides an overview of the key topics and trends in genetic factors and OA pathogenesis research. The high-frequency keywords suggest the current and potential future focus of this field, involving methods, mechanisms, and populations.

MicroRNA plays a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5’-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP-isomiR pairs were identified. Of note, rs6505162 was significantly associated with both 5’-extension of hsa-miR-423-3p and 5’-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNA.

In recent years, several industries have registered an impressive improvement in technological advances such as Internet of Things (IoT), e-commerce, vehicular networks, etc. These advances have sparked an increase in the volume of information that gets transmitted from different nodes of a computer network (CN). As a result, it is crucial to safeguard CNs against security threats and intrusions that can compromise the integrity of those systems. In this paper, we propose a machine mearning (ML) intrusion detection system (IDS) in conjunction with the Genetic Algorithm (GA) for feature selection. To assess the effectiveness of the proposed framework, we use the NSL-KDD dataset. Furthermore, we consider the following ML methods in the modelling process: decision tree (DT), support vector machine (SVM), random forest (RF), extra-trees (ET), extreme gradient boosting (XGB), and naïve Bayes (NB). The results demonstrated that using the GA algorithm has a positive impact on the performance of the selected classifiers. Moreover, the results obtained by the proposed ML methods were superior to existing methodologies.

The concept of genetic improvement in relation to biological control involves the exploitation of natural genetic variation for the benefit of existing biological control agents (BCAs). Despite recent calls for this process to be adopted in biological control research, there is no clear overview of the current state of research into genetic variation within a biological control context, including quantifiable estimates such as narrow-sense heritability (h²). In this systematic review, we aim to determine the current state of research on the genetic variation of biological control traits in natural enemies. After the searching process, screening for papers that can deliver on our research question reduced the initial 2,927 search hits to only a mere 69 papers for data extraction. Of these, the majority (73.6%) did not report quantitative values for genetic variation. Extracting the traits measured in these papers, we categorized them according to two approaches; the first related to fitness components, and the second related to biological control importance. This systematic review highlights the need for more rigorous reporting of the quantitative values of genetic variation to enable the successful genetic improvement of biological control agents.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

Determining genetic and non-genetic sources of variation in a breed is vital for the formulation of strategies for its conservation and improvement. The present study was aimed at estimating the (co)variance components and genetic parameters of Mecheri sheep by fitting six different animal models in the restricted maximum likelihood method, with a preliminary investigation on the performance of animals for non-genetic sources of variation. A total of 2616 lambs were studied, and varying levels of significance were found for the effect of period, season, parity of dam and birth type on different body weight traits. Direct heritability estimates derived from the best animal model for body weight at birth, 3 months, 6 months, 9 months and 12 months were 0.21, 0.24, 0.10, 0.15 and 0.09, respectively, and maternal heritabilities of the corresponding traits were 0.12, 0.05, 0.04, 0.04 and 0.04, respectively. The genetic correlations between body weight traits were all positive and moderate to strong except for birth weight with the other body weight traits. The significance of non-genetic factors studied in this work demanded a correction to improve the accuracy of the direct selection of lambs for body weight traits. The estimated genetic parameters identified the weaning weight as a selection criterion for the improvement in body weight of Mecheri lambs at different ages. Inbred individuals accounted for approximately 13% of the total population in the Mecheri sheep population studied. There were 877 founders in the population, and the actual effective size of the population was 128.48. The population's mean generation interval was 3.26. The mean inbreeding values ranged from 0.005 to 0.010 across generations. The population's average relatedness ranged from 0.001 to 0.014 across generations. Individual inbreeding was found to be 0.45 per cent for the entire population and 3.4 per cent for the inbred population.

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.

The research identified norovirus genotypes that circulated among Gambian children less than five years of age with diarrhoea during 2007-2012. The study highlights the importance of continuous surveillance for detecting the emergence of new norovirus genotypes.

Interferons were the original prototype cytokine system discovered in 20th-century research. As the name implies, they were originally thought to be synthesised and secreted between cells. Thanks to technological advances, the processes involved in protein secretion can be explained comparatively more clearly at both the genetic and biochemical levels. The discovery of interferon (IFN) occurred when genetic research was still in its infancy. Franklin and Wilkins discovered the structure and function of deoxyribonucleic acid (DNA) at the same time as Crick and Watson; however, Isaacs and Lindemann, two scientists, described the first IFN in 1957. Mutations can be caused by inherent genetic protein synthesis and during infection as well as within IFN regulation pathways affecting cell proliferation. This remains central to host cell IFN synthesis and effects through IFN protein receptor subunits defined by 6 protein domains. Type II IFN is key to immune cell function secreted by a variety of immune cells, mainly natural killer (NK) as well as T cells. Single–stranded and/or double–stranded RNA/DNA viruses, as well as bacterial infections (e.g., Escherichia coli) and fungal infections (e.g., Aspergillus), also affect IFN regulation. Pathogenic proteins utilise intra/extracellular proteins that sense foreign antigens like Toll–like Receptors (TLRs), affected by mutations within the human cellular IFN transduction pathways. Since the discovery of the third IFN type in 2003, when immune cell phenotypes were further characterised, questions remain about the immunological mechanisms contributing to the regulation of the innate and adaptive host immune system. Alterations in the synthesis of type I/II/III host IFNs can differentially and beneficially alter homeostatic cellular pathways in pathological disease, with type I IFN being synthesised in cancer as well as by homeostatic cells. Therefore, considered here are the overall IFN molecular, cell regulatory mechanisms in the context of immune cell research developments.

A 52-y/o asymptomatic male with history of hypertension, was referred to our Heart Failure Clinic due to report of hypertrophic cardiomyopathy, TTE with an increased end-diastolic thick-ness (basal inferoseptal of 23 mm, and basal anteroseptal of 21 mm). CMR demonstrated late gadolinium enhancement at the septum, anterior, inferolateral, and inferior walls with a mid-myocardial distribution, T1 mapping which reported an average T1 of 929 ms. A next-generation sequencing panel was requested. Results demonstrated hemizygosis, in the ga-lactosidase alpha gene, consistent with Fabry Disease. The replacement of the enzyme was start-ed. Extended familial genetic counseling and testing were done.

Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to its high interindividual and interpopulation variability. The lipid ratios: atherogenic index of plasma (AIP=log TG/HDL-C) and the Castelli risk index 2 (CI2=LDL-C/HDL-C) have been proposed as better predictors of cardiovascular risk, but the genetic variability associated to these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n=426) included males (40%) and females (60%) aged 18-52 years (mean 39 years), the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1E-6) the three former previously associated to blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1E-7) the latter previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP and CI2, highlighting the relation between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.

Within microeukaryotes, genetic and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellies), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.

Bermudagrass (Cynodon spp.) is one of the drought-resistant warm-season turfgrasses adapted to the southern and transitional zones in the United States. Multiple hybrid varieties have been developed and released for use as a turfgrass and others are in pipeline. Increasing genetic di-versity of commercial varieties is vital to tackle stress tolerance. A DNA profiling study of 21 experimental selections from the Oklahoma State University (OSU) turfgrass breeding program and 11 cultivars was conducted using 51 simple sequence repeat (SSR) primer pairs that spread across the bermudagrass genome. Pairwise genetic relationship analysis among the genotypes using 352 polymorphic bands showed genetic similarity coefficients ranging from 0.59 to 0.89. Cluster analysis using the un-weighted paired group method with arithmetic average (UPGMA) method grouped the entries into six clusters. Correlation analysis identified different levels of pairwise genetic relationship among the entries that largely reflected parental relationship. Di-rectional breeding and selection for cold hardiness or drought resistance created progeny that had distinct genetic diversity in the tested bermudagrasses. It is evident that an increase in genetic diversity of the existing cultivar pool with the release of one or more of the experimental selec-tions for commercial use will strengthen and improve bermudagrass systems.