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.

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.

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.

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.

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.

We find that the degeneracies and many peculiarities of the DNA genetic code may be described thanks to two closely related (fivefold symmetric) finite groups. The first group has signature $G=\mathbb{Z}_5 \rtimes H$ where $H=\mathbb{Z}_2 . S_4\cong 2O$ is isomorphic to the binary octahedral group $2O$ and $S_4$ is the symmetric group on four letters/bases. The second group has signature $G=\mathbb{Z}_5 \rtimes GL(2,3)$ and points out a threefold symmetry of base pairings. For those groups, the representations for the $22$ conjugacy classes of $G$ are in one-to-one correspondence with the multiplets encoding the proteinogenic amino acids. Additionally, most of the $22$ characters of $G$ attached to those representations are informationally complete. The biological meaning of these coincidences is discussed.

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.

Genetic code expansion has emerged as an enabling tool to provide insight into functions of understudied proteinogenic species such as small proteins and peptides, and to probe protein biophysics in the cellular context. Here we discuss recent technical advances and applications of genetic code expansion in cellular imaging of complex mammalian protein species, along with considerations and challenges upon using the method.

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.

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

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

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

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.

Aminoacyl-tRNA synthetases (aaRSs) originated from an ancestral bidirectional gene (mirror symmetry) and through the evolution of the genetic code the twenty aaRSs exhibit a symmetrical distribution in a 6-dimensional hypercube of the Standard Genetic Code. In this work, we assume a primeval RNY code, and the Extended Genetic RNA code type II which includes codons of the type YNY, YNR and RNR. Each of the 4 subsets of codons can be represented in a 4-dimensional hypercube. Altogether these 4 subcodes constitute the 6-dimensional representation of the SGC. We identify the aaRSs' symmetry groups in each of these hypercubes. We show that each of the four hypercubes contains the following sets of symmetries for the two known Classes of synthetases: RNY: dihedral group D2; YNY: binary group Z2; YNR: amplified octahedral group Oh; and RNR: binary group Z2. We demonstrate that for each hypercube, the group of symmetries of Class 1 is the same as the group of symmetries of Class 2. The biological implications of these findings are discussed.

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

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

The Kummer surface was constructed in 1864. It corresponds to the desingularisation of the quotient of a 4-torus by 16 complex double points. Kummer surface is kwown to play a role in some models of quantum gravity. Following our recent model of the DNA genetic code based on the irreducible characters of the finite group G5:=(240,105)≅Z5⋊2O (with 2O the binary octahedral group), we now find that groups G6:=(288,69)≅Z6⋊2O and G7:=(336,118)≅Z7⋊2O can be used as models of the symmetries in hexamer and heptamer proteins playing a vital role for some biological functions. Groups G6 and G7 are found to involve the Kummer surface in the structure of their character table. An analogy between quantum gravity and DNA/RNA packings is suggested.

In this study, we once again use a set of Fibonacci-like sequences to examine the symmetries within the genetic code. This time, our focus is on the physiological state of the amino acids, considering them as charged, in contrast to our previous work where they were seen as neutral. In a pH environment around 7.4, there are four charged amino acids. We utilize the properties of our sequences to accurately describe the symmetries in the genetic code table. These include Rumer’s symmetry, the third-base symmetry and the "ideal" symmetry, along with the "supersymmetry" classification schemes. We also explore the special chemical structure of the amino acid proline, presenting two perspectives—shCherbak’s view and the Downes-Richardson view, which perspectives are included in the description of the above-mentioned symmetries. Our investigation employs also elementary modular arithmetic to precisely describe the chemical structure of proline, connecting the two views seamlessly. Finally, our Fibonacci-like sequences prove instrumental in quickly establishing the multiplet structure of non-standard versions of the genetic code. We illustrate this with an example, showcasing the efficiency of our method in unraveling the complex relationships within the genetic code.

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.

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.

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.

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

The 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.

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.

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.

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.

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.

Pregnancy planning and genetic testing (PPGT) has emerged as a tool in reproductive healthcare, offering parents-to-be insight in their risks of having a child with a genetic disorder. This paper reviews the advantages, drawbacks and challenges associated with PPGT, providing some practical guidance for health care professionals. Advantages include identification of genetic risks, a possibility to informed reproductive decision-making, and the potential to reduce the parents-to-be risk for an affected child. Challenges and drawbacks include provision of service, ethical considerations, genetic counselling complexities, and the need to increase public and professional awareness by comprehensive education and accessibility. Practical guidance involves considerations for selecting appropriate candidates, counselling strategies, and how to integrate PPGT into existing healthcare frameworks. By addressing these factors, PPGT can offer an increased reproductive informed choice for the individual and the couple reducing the burden of disease in the family.

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.

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..

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.

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.

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.

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 generation of forensic DNA profiles consisting of single nucleotide polymorphisms (SNPs) is now being facilitated by wider adoption of next-generation sequencing (NGS) methods in casework laboratories. At the same time, and in part because of this advance, there is an intense focus on the generation of SNP profiles from evidentiary specimens for so-called forensic or investigative genetic genealogy (FGG or IGG) applications. However, FGG methods are constrained by the algorithms for genealogical database searches, which were designed for use with single-source profiles, and the fact that many forensic samples are mixtures. To enable the use of two-person mixtures for FGG, we developed a workflow, MixDeR, for the deconvolution of mixed SNP profiles. MixDeR, a flexible and easy to use R package and Shiny app, processes ForenSeq Kintelligence® (QIAGEN, Inc.) SNP genotyping results and directs deconvolution of the profiles in EuroForMix (EFM). MixDeR then filters the EFM outputs to produce inferred single-source genotypes in reports formatted for use with GEDmatch® PRO. An optional MixDeR output includes metrics that assist with testing and validation of the workflow. As the Shiny app provides a graphical user interface and the software is designed to be run offline, MixDeR should be suitable for use by any laboratory developing FGG capabilities, no matter their bioinformatic resources or expertise.

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 Amazonian shrub Myrciaria dubia (Kunth) McVaugh, known as "camu-camu", produces vitamin C-rich fruits of growing commercial interest. However, sustainable utilization requires assessment and protection of the genetic diversity of the available germplasm. We hypothesized that the ex situ M. dubia germplasm bank assembled from eight river basins across the Peruvian Amazon would harbor substantial genetic diversity and have a genetic population structure. This study aimed to (1) develop new polymorphic microsatellite markers, (2) characterize genetic diversity and validate the hypothesis in the ex situ germplasm, and (3) construct a core subset representing maximum allelic variability. Sixteen polymorphic microsatellite loci were developed using an enrichment approach. The evaluation of 336 genotypes from 43 accessions originating from eight river basins of the germplasm bank corroborated this hypothesis, revealing high gene diversity, with observed heterozygosity ranging from 0.468 to 0.644 and expected heterozygosity from 0.684 to 0.817 at the river basin level. Analysis of molecular variance showed a higher genetic variation within accessions and river basins, at 73% and 86%, respectively, than among accessions and river basins, at 27% and 14 %, respectively. Bayesian clustering detected the presence of ten genetic clusters, with several degrees of admixture among river basins. The Putumayo River basin showed a clear genetic homogeneity. A core collection of 84 genotypes was constructed, thus covering 86.7% of the global allelic diversity. These results have important implications for M. dubia conservation strategies and breeding programs, in demonstrating a need for genetic connectivity between populations but preserving unique genetic resources in isolated basins. These results validate the expected levels of diversity and population subdivision in a crop and stress the need to secure genetically diverse germplasms, underscoring the importance of thorough genetic characterization for ex situ germplasm management.

Clustering is a crucial at the same time challenging task in several application domains. It is important to incorporate the optimum feature finding into our clustering algorithms for getting better prediction accuracy but this is difficult when there is no or little information about the importance or relevance of features. To tackle this task in an efficient manner we employ the natural evolution process inherent in genetic algorithms (GA) to find the optimum features for clustering for the healthy aging dataset. In order to empirically verify the findings, genetic algorithms were combined with a number of clustering algorithms including parti-tional, density based as well as agglomerative. A variant of the popular KMeans algorithm, named KMeans++ gave the best performance on all performance metrics when combined with GA.

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.

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

Due to the fact that to date, the question of the origin of SARS-CoV-2 has not been resolved yet, the author analyzed the main advances in the development of genetic engineering of viruses that took place before the onset of the COVID-19 pandemic. The first artificial genetically modified viruses could appear in nature in the mid-1950s. The technique of nucleic acid hybridization was developed by the end-1960s. In the late 1970s, a method called the "reverse genetics" emerged to synthesize RNA and DNA molecules. In the early 1980-s, it became possible to combine the genes of different viruses and insert the genes of one virus into the genome of another virus. Since that time, the production of vector vaccines began. Currently, by modern technologies one can assemble any virus based on the nucleotide sequence available in the virus database or designed by a computer as a virtual model.Scientists around the world are invited to answer the call of Neil Harrison and Jeffrey Sachs of Columbia University, for a thorough and independent investigation into the origin of SARS-CoV-2. Only a full understanding of the origin of the new virus can minimize the likelihood of a similar pandemic in the future.

A total of 27 microsatellites markers , scattered all over the genom of barley, were used for characterization,and diversity analysis in 33 barley (Hordeum vulgare L.) accessions and cultivars of Algeria.Over the 27 genetic loci studied, 110 alleles were identified with a mean of 4.1 alleles per locus and the average polymorphism information content (PIC) of 0.46,the marker Ebma0806 showed the greatest value of PIC with 0.83.Genetic diversity at 27 microsatellite loci varied from 0 to 0.84 (Mean=0.50) for 33 Algerian cultivars. The genetic distance among the cultivars ranged from 0.2 to 0.85. Cluster analysis and principal coordinate analysis (PCoA) based on the SSR data clearly differentiate the all genotypes studied.

Bananas, a staple food globally and a key agricultural commodity, face a severe threat from the fungus Fusarium oxysporum form specialis cubense (Foc), significantly impacting production. Genetic improvement to develop resistant cultivars stands out as a crucial strategy to mitigate this disease. This study focused on assessing and recommending enhanced diploid banana varieties for resistance against Foc subtropical race 4 (ST4) and Foc race 1 (R1). Twenty-five improved diploids developed by Embrapa, Brazil, underwent evaluation. Utilizing a scale for internal symptoms at 90 days post-inoculation, genotypes were categorized from highly resistant to highly susceptible based on the internal symptom index. The diploid M53 exhibited high resistance to R1 and resistance to Foc ST4, while only the diploid CNPMF 0534 demonstrated complete resistance to both R1 and ST4, with resistance to the latter likely associated with penetration. These findings provide valuable insights for banana and plantain breeding programs, offering selected diploids for crossbreeding with commercial cultivars to develop new, resistant genotypes against Foc.

In T. gondii, as well as in other model organisms, gene knock-out using CRISPR-Cas9 is a suitable tool to identify the role of specific genes. The general consensus implies that only the gene of interest is affected by the knock-out. Is this really the case? In a previous study, we have generated knock-out (KO) clones of TgRH88_077450 (SRS29B; SAG1) which differed in the numbers of integrated dihydrofolate-reductase-thymidylate-synthase (MDHFR-TS) drug-selectable marker. Clones 18 and 33 had a single insertion of MDHFR-TS within SRS29B. Clone 6 was disrupted by the insertion of a short unrelated DNA-sequence, but the marker was integrated elsewhere. In clone 30, the marker was inserted into SRS29B and several other MDHFR-TS copies were found in the genome. KO and wild-type (WT) tachyzoites had similar shape, dimensions and vitality. This prompted us to investigate the impact of the genetic engineering as such on the overall proteome patterns of the four clones as compared to the respective WT. Comparative shotgun proteomics of the five strains was performed. Overall, 3236 proteins were identified. Principal component analysis of the proteomes revealed five distinct clusters corresponding to the five strains by both iTop3 and iLFQ algorithms. Detailed analysis of the differentially expressed proteins revealed that the target of the KO, srs29B, was lacking in all KO clones. Besides this protein, twenty other proteins were differentially expressed between KO clones and WT or between different KO clones. The protein exhibiting the highest variation between the five strains was srs36D encoded by TgRH_016110. The deregulated expression of SRS36D was further validated by quantitative PCR. Moreover, the transcript levels of three other selected SRS genes, namely SRS36B, SRS46, and SRS57 exhibited significant differences between individual strains. These results indicate that knocking out a given gene may affect the expression of other genes. Therefore, care must be taken when specific phenotypes are regarded as a direct consequence of the KO of a given gene.

Hand gesture recognition has many valuable applications in engineering and health care. This study proposes a novel model which can accurately distinguish hand gestures using forearm muscles' surface electromyogram (sEMG) signals. A deep learning algorithm with hyper parameters impacting the final model’s accuracy and a convolutional neural network (CNN) were employed in the recognition stage. The number of convolutional layers, kernels per layer, and neurons in the dense layer were selected for optimization, while the remaining parameters, such as the learning rate, batch size, and number of epochs, were chosen based on trial and error and prior knowledge. The optimal values for the selected hyperparameters were obtained using a genetic algorithm to achieve maximum recognition accuracy. The UC2018 Dual-Myo database was used for training and testing the model based on EMG signals characterizing the activity of eight different hand gestures. The final structure of the model consisted of two convolutional layers with 131 and 28 kernels, a dense layer with 111 neurons, and a softmax layer with eight neurons. Upon optimizing the hyperparameters using the genetic algorithm, the accuracy of the proposed model increased from 91.86% to 96.4% at best and 95.3% on average in real-time applications and 99.6% in an offline mode. Future work is warranted towards improving the architecture and the computational cost.

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

Capirona (Calycophyllum spruceanum Benth.) belongs to subfamily Ixoroideae, one of de major lineages in the Rubiaceae family, and is an important timber tree, with origin in the Amazon Basin and has widespread distribution in Bolivia, Peru, Colombia, and Brazil. In this study, we obtained the first complete chloroplast (cp) genome of capirona from department of Madre de Dios located in the Peruvian Amazon. High-quality genomic DNA was used to construct librar-ies. Pair-end clean reads were obtained by PE 150 library and the Illumina HiSeq 2500 platform. The complete cp genome of C. spruceanum has a 154,480 bp in length with typical quadripartite structure, containing a large single copy (LSC) region (84,813 bp) and a small single-copy (SSC) region (18,101 bp), separated by two inverted repeat (IR) regions (25,783 bp). The annotation of C. spruceanum cp genome predicted 87 protein-coding genes (CDS), 8 ribosomal RNA (rRNA) genes, 37 transfer RNA (tRNA) genes and 01 pseudogene. A total of 41 simple sequence repeats (SSR) of this cp genome were divided into mononucleotides (29), dinucleotides (5), trinucleotides (3), and tetranucleotide (4). Most of these repeats were distributed in the noncoding regions. Whole chloroplast genome comparison with the other six Ixoroideae species revealed that the small single copy and large single copy regions showed more divergence than invert regions. Finally, phylogenetic analysis resolved that C. spruceanum is a sister species to Emmenopterys henryi, and confirms its position within the subfamily Ixoroideae. This study reports for the first time the genome organization, gene content, and structural features of the chloroplast genome of C. spruceanum, providing valuable information for genetic and evolutionary studies in the genus Calycophyllum and beyond.

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

Rajasthan is a state located in the north-western part of India and it has been cited as a major route of human migration since ancient times. The present study was conducted to find out the genetic affinity of Rajasthani population with the population living in its east and the west. In particular, we compared them with the population of Pakistan which shares the common geographical boundary with the Rajasthan while also having a look at their inter and intra population affinities with the population belonging to other Indian states. We investigated the genetic structure and population parameters of Rajasthani populations obtained for twenty polymorphic autosomal STR loci from 669 unrelated individuals belonging to its three population groups including Mina, Gujjar and the admixed population of Rajasthan. The studied populations showed a wide range of genetic diversity and besides the genetic structure of the studied populations, it was found that the average heterozygosity value was highest among the populations of Rajasthan, possibly, because of gene flow from different directions. Various statistical analyses suggested that the Rajasthani populations had a higher affinity with the North Indian populations rather than with the Pakistani population.

Bemisia tabaci (Gennadius) is a polyphagous, highly destructive pest capable of vectoring viruses in most agricultural crops. Currently, information on the distribution and genetic diversity of B. tabaci in South Sudan is not available. The objectives of this study were to investigate the genetic variability of B. tabaci infesting sweet potato and cassava in South Sudan. Field surveys were conducted between August 2017 and July and August 2018 in 10 locations in Juba County, Central Equatoria State, South Sudan. Sequences of mitochondrial DNA cytochrome oxidase I (mtCOI) were used to determine the phylogenetic relationships between sampled B. tabaci. Six distinct genetic groups of B. tabaci were identified including three non-cassava haplotypes (Mediterranean (MED), Indian Ocean (IO) and Uganda) and three cassava haplotypes (Sub-Saharan Africa 1 sub-group 1 (SSA1-SG1), SSA1-SG3 and SSA2). MED predominated on sweet potato and SSA2 on cassava in all the sampled locations. The Uganda haplotype was also widespread, occurring in five of the sampled locations. This study provides important information on the diversity of B. tabaci species in South Sudan. A comprehensive assessment of the genetic diversity, geographical distribution, population dynamics and host range of B. tabaci species in South Sudan is vital for its effective management.

Human genetic studies have long been vastly Eurocentric, raising a key question about the generalizability of these study findings to other populations. Because humans originated in Africa, these populations retain more genetic diversity, and yet individuals of African descent have been tremendously underrepresented in genetic studies. The diversity in Africa affords ample opportunities to improve fine-mapping resolution for associated loci, discover novel genetic associations with phenotypes, build more generalizable genetic risk prediction models, and better understand the genetic architecture of complex traits and diseases subject to varying environmental pressures. Thus, it is both ethically and scientifically imperative that geneticists globally surmount challenges that have limited progress in African genetic studies to date while meaningfully including African investigators, as greater inclusivity and enhanced research capacity affords enormous opportunities to accelerate genomic discoveries that translate more effectively to all populations. We review the advantages and challenges of studying the genetic architecture of complex traits and diseases in Africa. For example, with greater genetic diversity comes greater ancestral heterogeneity; this higher level of understudied diversity can yield novel genetic findings, but some methods that assume homogeneous population structure and work well in European populations may work less well in the presence of greater diversity and heterogeneity in African populations. Consequently, we advocate for methodological development that will accelerate studies important for all populations, especially those currently underrepresented in genetics.

Drought and arsenic contamination pose a serious threat to global rice crop yield. Existing solutions focus on either heavy metal or drought remediation, but not both. Examination of the Oryza sativa metagenome via the National Center for Biotechnology Information (NCBI) database revealed promising candidates within the aquaporin gene family capable of efficiently mitigating both arsenic toxicity and drought stress. Rice cotyledons were genetically augmented with arsenic-resistant OsNIP2;1 and OsNIP3;2 genes, and drought-resistant OsPIP2;2 genes. In moderate drought conditions and 25 ppm arsenic-contaminated soil, transgenic plants showed drought tolerance and reduced translocation of arsenic from root to shoot. Soil arsenic levels plummeted from 25 ppm to 5 ppm, demonstrating the strategy's efficacy. Statistical significance was confirmed using T tests. Thus, aquaporin-augmented Oryza sativa offers a promising solution to mitigate both arsenic and drought stress in rice plants improving crop yield and facilitating soil decontamination.

The advancement of sequencing technology and molecular breeding methods have provided technical support and assurance for accurate breeding. Genomic Selection (GS) utilizes genomic information to improve livestock breeding and, it is more accurate and more efficient than traditional selection methods. GS has been widely applied in domestic animals breeding, especially in cattle. However, there is still limited study on the application and research of GS in sheep and goat. In this paper, we outlined the principle, analysis methods, the influential factors of GS, and elaborated on the research progress, challenges, and prospects of applying GS in sheep and goat breeding. Through the review of these aspects this paper is expected to provide valuable references for the implementation of GS in the field of sheep and goat breeding.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

it has been just over three years since SARS-CoV-2 viral infection was first known as causing severe acute and highly transmissible respiratory syndrome coronavirus. During one of the worst global pandemics of the last century, caused by the COVID-19 disease, under the persistent immune pressure exerted by the newest vaccines, the SARS-CoV-2 virus is fastly mutating and becoming less severe, but more contagious. On the other hand, some studies [1,2,3] indicate that the elderly COVID-19 patients or those who have reported a virulent episode of this infection, experience some long-lasting neurological complications, including encephalopathy, encephalitis, cerebrovascular disease, Parkinson’s disease (PD), Alzheimer’s disease (AD) and prion disease (PrD). So, there are several recent reports of patients [4,5] developing PrD following the SARS-CoV-2 infection, but, to the best of our knowledge, this is the first case reported in Italy on an association of the PRNP E200K somatic mutation with gCJD. The rising global prevalence neurodegenerative complications following COVID-19 disease adds urgency to the study of this potential relationship.

The COVID-19 pandemic has emphasized the crucial role of ventilation systems in mitigating cross-infections, especially in infectious disease hospitals. This study introduces a dual-design operation ventilation system that can operate under two sets of ventilation conditions for normal and epidemic times. A challenge is optimizing duct diameters for required airflow while maintaining hydraulic balance. We design a genetic algorithm with adaptive penalty factor, the velocity constraint and the improved crossover and mutation probability. The improved genetic algorithm is suitable for ventilation system networks, which can find a better air duct diameters combination to improve the hydraulic balance rate, and reduce the usage of air valves, resulting in efficient hydraulic balancing commissioning. Compared with the traditional genetic algorithm, it has a faster search speed and a better global search ability, which is effective for the optimal design of ventilation system networks.

Perceptual and statistical evidence has underlined voice characteristics of individuals affected by genetic syndromes different from that of normophonic subjects. In this paper we propose a procedure for the systematic collection of such pathological voices and the development of AI-based automatic tools to support differential diagnosis. Guidelines are provided concerning most suitable recording devices, vocal tasks and acoustical parameters, in order to simplify, speed up and make the whole procedure homogenous and replicable. The proposed procedure was applied to a set of 56 subjects, affected by Costello syndrome (CS), Down syndrome (DS), Noonan syndrome (NS) and Smith-Magenis syndrome (SMS). The whole database has been divided into three groups, respectively called: paediatric subjects (PS, individuals &lt; 12 years of age), female adults (FA) and male adults (MA) subjects. In line with literature results, the Kruskal-Wallis test and post-hoc analysis with Dunn-Bonferroni test highlighted several significant differences in acoustical features not only between healthy subjects and patients, but also across syndromes within PS, FA and MA groups. Machine learning provided for the PS group a k-nearest neighbour classifier with 75% accuracy, for the FA group a support vector machine (SVM) model with 84% accuracy and for the MA group a SVM model with 97% accuracy. These preliminary results suggest that the proposed procedure, based on acoustical analysis and AI, might be helpful for an effective non-invasive automatic characterization of genetic syndromes.

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder caused by hemizygous microdeletion of the long arm of chromosome 22. It is now known to have a heterogenous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioral phenotypes and psychiatric illness. The purpose of our paper is to present the case of a fetus diagnosed with a rare and complex cardiac malformation (interrupted aortic arch (IAA) type B, large malalignment-type ventricular septal defect (VSD), pulmonary valve dysplasia, aberrant right subclavian artery (ARSA). The result of the genetic testing revealed 22q11.2 deletion and after genetic counselling the patient decided to continue the pregnancy. She was regularly followed until delivery which took place in Germany so that neonatal cardiac surgery could be performed in an experienced center for cardiac malformations. We emphasize on the ultrasound aspects regarding the cardiac anomaly and specific features of 22q11.2DS in a continuous manner from diagnosis until delivery.

This study is focused on an optimal sizing method based on genetic algorithms (GA) in order to design a high-performance photovoltaic system that would be installed in the Alioune Diop University of Bambey, Senegal. The multi-objective optimization allowed us to find a better trade- off between the Total Life Cycle cost (TLCC) and the Loss of Power Supply Probability (LPSP). The goal is to minimize the TLCC while maintaining a good satisfactory of the system with a desired LPSP, under certain constraints. The expressions of the TLCC and the LPSP are established according to the total photovoltaic energy and the battery capacity. The toolbox of Matlab software is used to implement the optimization problem with twelve blocks of the site and its different corresponding loads. The obtained results have led to a several combinations of the photovoltaic and battery capacities of which the best one is selected based on the lowest LPSP, that guaranteed a better load coverage during the night. The results of this proposed method are compared with intuitive method that has been firstly applied. For the block with the lowest load demand, the proposed optimization model leads to a reduction a reduction of 70% and 48% in the storage capacity and the TLCC respectively for a LPSP of 0.007 %.

Strawberry is produced in tropical regions using imported cultivars adapted to temperate and subtropical climates. These cultivars, under tropical conditions, produce below their genetic potential. Through multivariate analyses, the objective was to evaluate and select short-day strawberry genotypes based on intraspecific crosses, product characteristics, and fruit quality. The genotypes were obtained from the cross between 'Camino Real' (female parent) and the first-generation genotypes RVCA16, RVCS44, RVFS06, RVFS07, and RVDA11 (male parent), obtained in previous selections. The experimental design consisted of augmented blocks with standard controls, consisting of first-generation genotypes and commercial cultivars. The fruits were harvested and evaluated for productivity and post-harvest characteristics: Total Fruit Mass (MTF); Total Number of Fruits (TFN); Average Fruit Mass (AFM); Commercial Fruit Mass (CFM); Fruit Commercial Number (CFN); Average Commercial Mass of Fruits (ACFM); Total Soluble Solids (TSS); Firmness (F); Brightness (L); Hue Angle (°Hue); Chroma (C). The selection index of Mulamba and Mock (1978) was used with an intensity of 3% to obtain superior genotypes and submitted to multivariate analysis for comparative purposes. Of the 1500 genotypes evaluated, it was possible to select 44 genotypes with characteristics superior to the 13 controls. The RVDA11CR59 genotype showed better values for the attributes of interest, but the RVCS44CR population, from the cross between 'Camino Real' × RVCS44 ('Camarosa' × 'Sweet Charlie'), obtained the highest number (16) of individuals among those selected. Significant traits had high heritability but were not necessarily reflected in high selection gain. Coefficients of genetic variation were high, indicating sufficient genetic variability to select genotypes for these traits. When multivariate analyses were used, it was possible to group the selected genotypes into the same cluster according to the similarity and balance in the responses to the evaluated variables, demonstrating that these analyses help other parameters choose superior genotypes. The multivariate analysis allowed the selection of more balanced genotypes for production and post-harvest traits for tropical climates.

Andalusia is a Spanish region that is home to numerous minority varieties due to its diversity and territorial extension, offering the local viticulture the possibility of diversifying its wine production. The molecular identification of 98 specimens from six areas with a winemaking tradition in Andalusia was carried out between the years 2020 and 2022. Thirteen microsatellite markers were used in this study, including the nine recommended by the OIV. 31 different genotypes were obtained, 20 of which corresponded to profiles of already described varieties (11 of them are of minority cultivation in Andalusia: 'Rojal Tinto', 'Beba', 'Zurieles', 'Rome', 'Hebén', 'Mollar Cano', 'Listán Prieto', 'Listán del Condado', 'Jarrosuelto', 'Negra Dorada' and 'Mantúo de Pilas'), while the other 11 profiles did not match with previously identified varieties. This profiles were integrated into the database of the IFAPA “Rancho de la Merced” Germplasm Bank. The eco-geographical groups of the new identified genotypes were determined through analysis of genetic diversity. The presence of the Grapevine Fanleaf Virus, the Grapevine Fleck Virus and the Grapevine Leafroll associated Viruses was also analyzed using an ELISA test due to the necessity of having certifiable clones of the new varieties for their potential interest in being authorized for its cultivation in Spain.

Different types of disasters, whether natural or human character, lead to the significant loss of human lives. In the latter case, the quick action of identification of corpses and human remains is mandatory. There are a variety of protocols to identify victims, however, genetics is one of the tools that allow an exact identification of the victim. However, several factors may interfere with this identification, from the biological samples’ degradation not allowing the analysis of nuclear information, to failure to dispose of biological samples from family members. Access to certain family members could be a determinant of the proper choice of genetic markers that allow the identification of the victim, or his/her inclusion in a given genetic maternal or paternal lineage. With the new advances in the genetic field, it is expected to allow soon the identification of victims from disasters only with his/her biological postmortem samples, being possible to draw a robot portrait and its most likely physical characteristics. In all cases, genetics is the only modern tool with universal character and can be used in essentially all biological samples, giving and identification of more or less accurate statistical character, depending on whether nuclear or lineage markers are used.

Japanese encephalitis virus (JEV) causes acute viral encephalitis in humans and reproductive disorders in pigs. JEV emerged during the 1870s in Japan and since that time, JEV has been transmitted exclusively throughout Asia, according to known reporting and sequencing records. A recent JEV outbreak occurred in Australia which affected commercial piggeries across different temperate southern Australian states and caused confirmed infections in humans. A total of 47 human cases and seven deaths were reported. The recent evolving situation of JEV needs to be reported due to its continuous circulation in endemic regions and spread to non-endemics areas. Here, we reconstructed the phylogeny and population dynamics of JEV using recent JEV isolates for the future perception of disease spread. Phylogenetic analysis shows the most recent common ancestor occurred about 3120 years ago (YA) (95% Highest posterior density [HPD], 2680 to 3715). Our results of the Bayesian skyline plot (BSP) demonstrates that JEV demography lacks fluctuations for the last two decades, but it shows that JEV genetic diversity has increased during the last ten years. This indicates the potential JEV replication in the reservoir host, which is helping it to maintain its genetic diversity, and to continue its dispersal into non-endemic areas. The continuous spread in Asia and recent detection from Australia further support these findings. Therefore, an enhanced surveillance system is needed along with precautionary measures such as regular vaccination and mosquito control to avoid future JEV outbreaks.

Herbivores have evolved several strategies to cope with plant defences. Some herbivores are able to resist toxic compounds, while others can manipulate host immunity. Previously it was found that spider mites collected from non-solanaceous wild host plants consist mostly of individuals that induce tomato defences, but also at low frequencies of individuals that can suppress these defences. Also, it has been shown that mites collected from non-solanaceous plants can adapt to tomato by evolving traits that allow them to suppress defences. Hence, we wanted to know if this trait is also common among mites naturally occurring on tomatoes. Here, we compared three T. urticae populations sampled from tomato at three field sites, and also an outbred population created from them through controlled crosses. We then assessed their fecundity on wild-type (WT) tomato plants and def-1 mutants impaired in inducible JA-defences. We also assessed the magnitude of JA defences they induce in WT plants to discriminate between resistant types (high induction and high performance) and those that can suppress defences (low induction, high performance). We then aligned these data with data on variation in mitochondrial DNA cytochrome oxidase I (COI) and effector 84 (a suppressor of JA-defences in planta), in order to compare genetic diversity patterns among mite lines that induce or suppress defences. We found that suppression is the dominant phenotype in mite strains collected from field-grown tomatoes and that inducers and suppressors predominantly cluster in distinct effector 84 clades. We speculate that effector allelic diversity may be subject to natural selection when these mites colonize a novel host plant, promoting traits to cope with plant resistance, such as defence suppression, which facilitates adaptation.

The mutation databases have vital importance in detecting genetic mutation and their corresponding phenotypes. The emergence of next generation sequencing genetic technologies has accelerated this process, and the growth of genetic disease identification has created a need for quality control and documentation of mutation-related information. Ethnic-specific mutation databases offer valuable information for researchers, and the article evaluates the homogeneity and effectiveness of these databases. The aim to raise awareness of NEMDBs to healthcare professionals, the general public, and researchers studying genetic disorders. The article also recommendations to improve the effectiveness of these databases.

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide one suicide occurs every 40 seconds, making it a major health problem. Studies in families have suggested that suicide has a genetic component, around the world studies have been carried out in search of genetic variants associated with suicidal behavior, these variants could be useful as potential biomarkers to identify people at risk of suicide. In this area in Mexico, some studies of variants in genes related to neurotransmission and other important pathways have been carried out and a possible association of variants located in genes has been suggested: SLC6A4, SAT-1, TPH-2, ANKK1, GSHR, SCARA50, RGS10, STK33, COMT, and FKBP5. This systematic review shows the genetic studies on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, said variants in the future could be used as potential biomarkers to identify people at risk of suicide.

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

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

Non-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damages throughout the cell cycle, and is specifically important for homeostasis of post-mitotic neurons and developing lymphocytes. Neuronal apoptosis increases in the mice lacking NHEJ factors Ku70 and Ku80. Inactivation of other NHEJ genes, either Xrcc4 or Lig4, leads to massive neuronal apoptosis in the central nervous system (CNS) that correlates with embryonic lethality in mice. Inactivation of either Paxx, Mri or Dna-pkcs NHEJ gene results in normal CNS development due to compensatory effects of Xlf. Combined inactivation of Xlf/Paxx, Xlf/Mri and Xlf/Dna-pkcs, however, results in late embryonic lethality and high levels of apoptosis in CNS. To determine the impact of NHEJ factors on early stages of neurodevelopment, we isolated neural stem and progenitor cells from mouse embryos and investigated proliferation, self-renewal and differentiation capacity of these cells lacking either Xlf, Paxx, Dna-pkcs, Xlf/Paxx or Xlf/Dna-pkcs. We found that XLF, DNA-PKcs and PAXX maintain the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models.

Nuclear pollution is an urgent environmental issue as a consequence of rapid industrialization and nuclear accidents in the past. Remediation of nuclear polluted sites using microbial vital activity (bioremediation) is a promising approach to recover contaminated areas in an environmentally friendly and cost-saving way. At the same time, the number of known bacterial and archaeal species able to withstand extremely high doses of ionizing radiation is steadily growing every year, together with growing knowledge about mechanisms of radioresistance. This opens up new opportunities for developing new biotechnological solutions. However, these data are often not systemized and it can be difficult to access. Here, we present the Determinants of Radioresistance Database, or DetR DB (http://extremebiolab.com/detr-db/), gathering a comprehensive catalog of radioresistant microbes and their molecular and genetic determinants of enhanced ionizing radiation tolerance. The database provides search tools including taxonomy, common gene name, and BLAST. DetR DB will be a useful tool for research community by facilitating the extraction of the necessary information to help further analysis of radiation-resistant mechanisms.

The rapid spread of the coronavirus disease 2019 (COVID-19) is a serious threat to public health systems globally and is subsequently, a cause of anxiety and panic within human society. Understanding the mechanisms and reducing the chances of having severe symptoms from COVID-19 will play an essential role in treating the disease, and become an urgent task to calm the panic. However, the COVID-19 test developed to identify virus carriers is unable to predict symptom development in individuals upon infection. Experiences from other plagues in human history and COVID-19 statistics suggest that genetic factors may determine the compliance with the virus, i.e., severe, mild, and asymptomatic. Here, a hypothesis is put forward based on the epidemiological characteristics and traits of COVID-19, and our gene expression analysis. It proposes that COVID-19 inactivation in the blood by blocking virus entry into other internal organs for reproduction through the blood circulation after lung cell invasion prevents severe symptoms. Additionally, we investigated a genetic connection between candidate genes and severe COVID-19 symptoms through the utilization of strategies combining hypothesis and data-driven approaches. A list of genes and important SNPs that require further investigation to aid the screening of individuals who may suffer severe illness if exposed to the virus is present. Those individuals should be intensively safeguarded and prioritised for treatment. Concurrently to further research on the COVID-19 pathogenesis, our results also offer a new research strategy for pandemic prevention and health maintenance.

Dioscorea praehensilis Berth is one of the wild yam species resistance to many yam disease (yam anthracnose disease and yam mosaic virus) grow in Ghana especially in the cocoa grown regions of the country. It is a crucial crop that has been known to contribute to poverty reduction and food gap. Genetic diversity in this yam species has been discovered to be eroding and neglected. In this study we evaluated the genetic diversity among 43 D. praehensilis collected from Ghana using simple sequence repeat (SSR). Using 11 SSR marker, a total of 99 number of alleles were generated with an average of 8.48 alleles per locus. The mean gene diversity was 0.81, mean polymorphism information content was 0.82 while mean Shannon information index was 1.94. Principal coordinate analysis (PCoA) revealed a contribution of 40.16% of the first three coordinate axes and grouped the 43 morphotypes into 2 groups while hierarchical cluster through UPGMA revealed the presence of 3 main clusters. Molecular variance (AMOVA) alongside the Fst revealed low genetic diversity and differentiation among accessions and population. Result of this study assess the genetic diversity and will facilitate the use D. praehensilis as sources of resistance gene into yam breeding program.

The rapid and extensive loss of biodiversity globally has resulted in an increased urgency to capture and conserve the diversity which is present, including genetic diversity within species. However, for many species there is currently no detailed genetic data available to inform the collection and use of material held in ex situ collections and this can hamper the consideration of genetic issues and reduce the likelihood collection represent the diversity present. Even in the absence of direct genetic data, however, it is possible to consider genetic issues using the existing theoretical and empirical evidence-based and biological, ecological and demographic data for a given species. Here a framework to facilitate the consideration of genetic diversity and genetic issues, even where genetic data is lacking, is presented.

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

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

Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.