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The dialogue between population genetics and evolutionary biology, which historically followed separate paths, has now developed into a complex and interdisciplinary field of study [...].

Theodosius Dobzhansky famously wrote in 1973 that "nothing in biology makes sense except in the light of evolution" [[1]], laying the foundations for the Modern Synthesis that combined population genetics with evolutionary biology and bridged the gap between geneticists and naturalists. Population genetics study the genetic diversity and structure of populations and all the processes involved [[2]]. Today, population genetics theory is inarguably the theoretical backbone of the Modern Synthesis, and all this progress and the combination of population and evolutionary genetics and genomics have provided answers to biologically important questions in a wide range of areas of research. Finally, organelle genomes can also provide a better understanding of evolution, speciation, and population divergence, and mitochondrial DNA (mtDNA), with its intrinsic properties, is extremely valuable for evolutionary and population genetic studies. [Extracted from the article]

The aim of this study was to investigate the effect of sunlight on the degradation of DNA samples taken from blood stains from different types of surfaces. A blood sample obtained from a single male donor was placed on seven different surfaces (galvanized sheet, iron rod, newspaper, white printer paper, glass, soil, and ceramic panel). Samples were kept, during a 4-week summer period, in a room, but next to an open window. Every 7 days, 1 mm2 of blood sample was collected from each substrate and stored in labeled tube for later analysis. DNA was extracted with the Chelex method, amplified using AmpFISTRTM MinifilerTM Plus Amplification Kit, and quantified using a QuantifilerTM Human DNA Quantification kit. After 7 days of sun exposure, the highest DNA concentration was determined to be from the sample from a galvanized sheet stain, followed by, in order of decreasing concentration, the ceramic panel, glass, newspaper, iron rod, and white printer paper surface. As expected, the DNA concentration from all samples decreased as the sunlight exposure time progressed. The results obtained after the amplification in the MiniFilerTM system were in correlation with the DNA concentrations measured by the qPCR method for all samples, except for the glass, soil, and white printer paper samples. The obtained data show that DNA degradation is correlated to the length of sunlight exposure and to the type of surface the samples are collected from. A negative qPCR result does not mean negative PCR amplification in the STR system; therefore, both methods should be applied when analyzing forensic samples collected from trace evidence. [ABSTRACT FROM AUTHOR]

Handwritten documents may contain probative DNA, but most crime laboratories do not process this evidence. DNA recovery should not impair other evidence processing such as latent prints or indented writing. In this study, single fingermarks on paper were sampled with flocked swabs, cutting, and dry vacuuming. In addition, two extraction methods were compared for the sample type. DNA yields were low across all methods; however, this work confirms the ability to recover DNA from paper and the usefulness of the vacuum sampling method combined with the Chelex-Tween method. Stability of touch DNA deposits were compared over an 11-month period to better understand degradation that may occur over time. No significant difference in DNA recovery was observed, suggesting DNA deposits on paper are stable over an 11-month span. [ABSTRACT FROM AUTHOR]

When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is fundamental, including a thorough personal and familial history, along with accurate physical examination and additional investigations. Especially when the clinical picture is uncertain, it is important to remember that certain genetic conditions can cause bleeding inside the brain, which may resemble NAHI. Pediatric strokes occurring around the time of birth can also be an initial sign of undiagnosed genetic disorders. Hence, it is crucial to conduct a thorough evaluation, including genetic testing, when there is a suspicion of NAHI but the symptoms are unclear. In these cases, a characteristic set of symptoms is often observed. This study aims to summarize some of the genetic causes of hemorrhagic stroke in the pediatric population, thus mimicking non-accidental head injury, considering elements that can be useful in characterizing pathologies. A systematic review of genetic disorders that may cause ICH in children was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We selected 10 articles regarding the main genetic diseases in stroke; we additionally selected 11 papers concerning patients with pediatric stroke and genetic diseases, or studies outlining the characteristics of stroke in these patients. The disorders we identified were Moyamoya disease (MMD), COL4A1, COL4A2 pathogenic variant, Ehlers–Danlos syndrome (E-D), neurofibromatosis type 1 (Nf1), sickle cell disease (SCD), cerebral cavernous malformations (CCM), hereditary hemorrhagic telangiectasia (HHT) and Marfan syndrome. In conclusion, this paper provides a comprehensive overview of the genetic disorders that could be tested in children when there is a suspicion of NAHI but an unclear picture. [ABSTRACT FROM AUTHOR]

Protein and nucleic acid binding site prediction is a critical computational task that benefits a wide range of biological processes. Previous studies have shown that feature selection holds particular significance for this prediction task, making the generation of more discriminative features a key area of interest for many researchers. Recent progress has shown the power of protein language models in handling protein sequences, in leveraging the strengths of attention networks, and in successful applications to tasks such as protein structure prediction. This naturally raises the question of the applicability of protein language models in predicting protein and nucleic acid binding sites. Various approaches have explored this potential. This paper first describes the development of protein language models. Then, a systematic review of the latest methods for predicting protein and nucleic acid binding sites is conducted by covering benchmark sets, feature generation methods, performance comparisons, and feature ablation studies. These comparisons demonstrate the importance of protein language models for the prediction task. Finally, the paper discusses the challenges of protein and nucleic acid binding site prediction and proposes possible research directions and future trends. The purpose of this survey is to furnish researchers with actionable suggestions for comprehending the methodologies used in predicting protein–nucleic acid binding sites, fostering the creation of protein-centric language models, and tackling real-world obstacles encountered in this field. [ABSTRACT FROM AUTHOR]

Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs' evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities. Methods: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children's Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position. Data were organized using the "My Bibliography" tool on the National Center for Biotechnology Information website and a Research Electronic Data Capture database created to initially collect manuscripts published through 30 June 2020. A subsequent survey captured publications through 5 February 2024. Results: An amount of 52 of 120 (43%) GCs shared their curriculum vitae/papers. 992 unique publications were identified from 1986 to 2024. Since 2013, no less than 32 papers were published annually by Section members and no less than 10 GCs contributed to publications yearly. Impact factors typically averaged >5.0 per year. Areas of foci diversified considerably since 2015. Conclusions: Here, we establish that GCs indeed contribute to scholarly work as evidenced by the number of publications alone. The establishment of an academic home may have contributed, given publications increased concurrent to launching the Section, providing a model for organizing GCs at institutions nationally and internationally. Highlighting such achievements will foster the expansion of GC roles in the era of precision genomic medicine and therapy. Considering ways to support GCs towards expanding these activities is equally important. [ABSTRACT FROM AUTHOR]

Bones and teeth represent a common finding in ancient DNA studies and in forensic casework, even after a long burial. Genetic typing is the gold standard for the personal identification of skeletal remains, but there are two main factors involved in the successful DNA typing of such samples: (1) the set-up of an efficient DNA extraction method; (2) the identification of the most suitable skeletal element for the downstream genetic analyses. In this paper, a protocol based on the processing of 0.5 g of bone powder decalcified using Na2EDTA proved to be suitable for a semi-automated DNA extraction workflow using the Maxwell® FSC DNA IQ™ Casework Kit (Promega, Madison, WI, USA). The performance of this method in terms of DNA recovery and quality was compared with a full demineralisation extraction protocol based on Qiagen technology and kits. No statistically significant differences were scored according to the DNA recovery and DNA degradation index (p-values ≥ 0.176; r ≥ 0.907). This new DNA extraction protocol was applied to 88 bone samples (41 femurs, 19 petrous bones, 12 metacarpals and 16 molars) allegedly belonging to 27 World War II Italian soldiers found in a mass grave on the isle of Cres (Croatia). The results of the qPCR performed by the Quantifiler Human DNA Quantification kit showed values above the lowest Limit of Quantification (lLOQ; 23 pg/µL) for all petrous bones, whereas other bone types showed, in most cases, lower amounts of DNA. Replicate STR-CE analyses showed successful typing (that is, >12 markers) in all tests on the petrous bones, followed by the metacarpals (83.3%), femurs (52.2%) and teeth (20.0%). Full profiles (22/22 autosomal markers) were achieved mainly in the petrous bones (84.2%), followed by the metacarpals (41.7%). Stochastic amplification artefacts such as drop-outs or drop-ins occurred with a frequency of 1.9% in the petrous bones, whereas they were higher when the DNA recovered from other bone elements was amplified (up to 13.9% in the femurs). Overall, the results of this study confirm that petrous bone outperforms other bone elements in terms of the quantity and quality of the recovered DNA; for this reason, if available, it should always be preferred for genetic testing. In addition, our results highlight the need for accurate planning of the DVI operation, which should be carried out by a multi-disciplinary team, and the tricky issue of identifying other suitable skeletal elements for genetic testing. Overall, the results presented in this paper support the need to adopt preanalytical strategies positively related to the successful genetic testing of aged skeletal remains in order to reduce costs and the time of analysis. [ABSTRACT FROM AUTHOR]

Vitamin D requires activation to show its pharmacological effect. While most studies investigate the association between vitamin D and disease, only a few focus on the impact of vitamin D metabolism gene polymorphisms (vitDMGPs). This bibliometric study aims to provide an overview of current publications on vitDMGPs (CYP27B1, CYP24A1, CYP2R1, CYP27A1, CYP2R1, DHCR7/NADSYN1), compare them across countries, affiliations, and journals, and inspect keywords, co-citations, and citation bursts to identify trends in this research field. CiteSpace© (version 6.1.R3, Chaomei Chen), Bibliometrix© (R version 4.1.3 library, K-Synth Srl, University of Naples Federico II, Naples, Italy), VOSviewer© (version 1.6.1, Nees Jan van Eck and Ludo Waltman, Leiden University, Leiden, Netherlands) and Microsoft® Excel 365 (Microsoft, Redmond, Washington, USA) classified and summarized Web of Science articles from 1998 to November 2022. We analyzed 2496 articles and built a timeline of co-citations and a bibliometric keywords co-occurrence map. The annual growth rate of vitDMGPs publications was 18.68%, and their relative research interest and published papers were increasing. The United States of America leads vitDMGPs research. The University of California System attained the highest quality of vitDMGPs research, followed by the American National Institutes of Health and Harvard University. The three productive journals on vitDMGPs papers are J. Steroid. Biochem. Mol. Biol., PLOS ONE, and J. Clin. Endocrinol. Metab. We highlighted that the vitDMGPs domain is relatively new, and many novel research opportunities are available, especially those related to studying single nucleotide polymorphisms or markers in a specific gene in the vitamin D metabolism cycle and their association with disease. Genome-wide association studies, genetic variants of vitDMGPs, and vitamin D and its role in cancer risk were the most popular studies. CYP24A1 and CYB27A1 were the most-studied genes in vitDMGPs. Insulin was the longest-trending studied hormone associated with vitDMGPs. Trending topics in this field relate to bile acid metabolism, transcriptome and gene expression, biomarkers, single nucleotide polymorphism, and fibroblast growth factor 23. We also expect an increase in original research papers investigating the association between vitDMGPs and coronavirus disease 2019, hypercalcemia, Smith–Lemli–Opitz syndrome, 27-hydroxycholesterol, and mendelian randomization. These findings will provide the foundations for innovations in the diagnosis and treatment of a vast spectrum of conditions. [ABSTRACT FROM AUTHOR]

Bioinformatics is a rapidly developing field enabling scientific experiments via computer models and simulations. In recent years, there has been an extraordinary growth in biological databases. Therefore, it is extremely important to propose effective methods and algorithms for the fast and accurate processing of biological data. Sequence comparisons are the best way to investigate and understand the biological functions and evolutionary relationships between genes on the basis of the alignment of two or more DNA sequences in order to maximize the identity level and degree of similarity. This paper presents a new version of the pairwise DNA sequences alignment algorithm, based on a new method called CAT, where a dependency with a previous match and the closest neighbor are taken into consideration to increase the uniqueness of the CAT profile and to reduce possible collisions, i.e., two or more sequence with the same CAT profiles. This makes the proposed algorithm suitable for finding the exact match of a concrete DNA sequence in a large set of DNA data faster. In order to enable the usage of the profiles as sequence metadata, CAT profiles are generated once prior to data uploading to the database. The proposed algorithm consists of two main stages: CAT profile calculation depending on the chosen benchmark sequences and sequence comparison by using the calculated CAT profiles. Improvements in the generation of the CAT profiles are detailed and described in this paper. Block schemes, pseudo code tables, and figures were updated according to the proposed new version and experimental results. Experiments were carried out using the new version of the CAT method for DNA sequence alignment and different datasets. New experimental results regarding collisions, speed, and efficiency of the suggested new implementation are presented. Experiments related to the performance comparison with Needleman–Wunsch were re-executed with the new version of the algorithm to confirm that we have the same performance. A performance analysis of the proposed algorithm based on the CAT method against the Knuth–Morris–Pratt algorithm, which has a complexity of O(n) and is widely used for biological data searching, was performed. The impact of prior matching dependencies on uniqueness for generated CAT profiles is investigated. The experimental results from sequence alignment demonstrate that the proposed CAT method-based algorithm exhibits minimal deviation, which can be deemed negligible if such deviation is considered permissible in favor of enhanced performance. It should be noted that the performance of the CAT algorithm in terms of execution time remains stable, unaffected by the length of the analyzed sequences. Hence, the primary benefit of the suggested approach lies in its rapid processing capabilities in large-scale sequence alignment, a task that traditional exact algorithms would require significantly more time to perform. [ABSTRACT FROM AUTHOR]

Consumer perception of beef is heavily influenced by overall meat quality, a critical factor in the cattle industry. Genomics has the potential to improve important beef quality traits and identify genetic markers and causal variants associated with these traits through genomic selection (GS) and genome-wide association studies (GWAS) approaches. Transcriptomics, proteomics, and metabolomics provide insights into underlying genetic mechanisms by identifying differentially expressed genes, proteins, and metabolic pathways linked to quality traits, complementing GWAS data. Leveraging these functional genomics techniques can optimize beef cattle breeding for enhanced quality traits to meet high-quality beef demand. This paper provides a comprehensive overview of the current state of applications of omics technologies in uncovering functional variants underlying beef quality complexities. By highlighting the latest findings from GWAS, GS, transcriptomics, proteomics, and metabolomics studies, this work seeks to serve as a valuable resource for fostering a deeper understanding of the complex relationships between genetics, gene expression, protein dynamics, and metabolic pathways in shaping beef quality. [ABSTRACT FROM AUTHOR]

With the advancement of terahertz technology, unveiling the mysteries of terahertz has had a profound impact on the field of biomedicine. However, the lack of systematic comparisons for gene expression signatures may diminish the effectiveness and efficiency of identifying common mechanisms underlying terahertz effects across diverse research findings. We performed a comprehensive review and meta-analysis to compile patterns of gene expression profiles associated with THz radiation. Thorough bibliographic reviews were conducted, utilizing the PubMed, Embase, Web of Science, and ProQuest databases to extract references from published articles. Raw CEL files were obtained from Gene Expression Omnibus and preprocessed using Bioconductor packages. This systematic review (Registration No. CDR42024502937) resulted in a detailed analysis of 13 studies (14 papers). There are several possible mechanisms and pathways through which THz radiation could cause biological changes. While the established gene expression results are largely associated with immune response and inflammatory markers, other genes demonstrated transcriptional outcomes that may unravel unknown functions. The enrichment of genes primarily found networks associated with broader stress responses. Altogether, the findings showed that THz can induce a distinct transcriptomic profile that is not associated with a microthermal cellular response. However, it is impossible to pinpoint a single gene or family of genes that would accurately and reliably justify the patterns of gene expression response under THz exposure. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, highly instructive, and inspiring for future advances in medicine. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent β-thalassemia has renewed hope for treating other hematologic diseases, including patients with a germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-inspired gene therapies. The purpose of this paper is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy, preceded by a brief description of the current tools being used in clinical genome editing; and third, a presentation of the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with a germline predisposition to hematologic malignancies. [ABSTRACT FROM AUTHOR]

The Whirly (WHY) gene family, functioning as transcription factors, plays an essential role in the regulation of plant metabolic responses, which has been demonstrated across multiple species. However, the WHY gene family and its functions in soybean remains unclear. In this paper, we conducted genome-wide screening and identification to characterize the WHY gene family. Seven WHY members were identified and randomly distributed across six chromosomes. The phylogenetic evolutionary tree of WHY genes in soybean and other species was divided into five clades. An in-depth analysis revealed that segmental duplications significantly contributed to the expansion of GmWHYs, and the GmWHY gene members may have experienced evolutionary pressure for purifying selection in soybeans. The analysis of promoter Cis-elements in GmWHYs suggested their potential significance in addressing diverse stress conditions. The expression patterns of GmWHYs exhibited tissue-specific variations throughout the different stages of soybean development. Additionally, six GmWHY genes exhibited different responses to low phosphate stress. These findings will provide a theoretical basis and valuable reference for the future exploration of WHY gene function. [ABSTRACT FROM AUTHOR]

de Magalhães has shown recently that most human genes have several papers in PubMed mentioning cancer, leading the author to suggest that every gene is associated with cancer, a conclusion that contradicts the widely held view that cancer is driven by a limited number of cancer genes, whereas the majority of genes are just bystanders in carcinogenesis. We have analyzed PubMed to decide whether publication metrics supports the distinction of bystander genes and cancer genes. The dynamics of publications on known cancer genes followed a similar pattern: seminal discoveries triggered a burst of cancer-related publications that validated and expanded the discovery, resulting in a rise both in the number and proportion of cancer-related publications on that gene. The dynamics of publications on bystander genes was markedly different. Although there is a slow but continuous time-dependent rise in the proportion of papers mentioning cancer, this phenomenon just reflects the increasing publication bias that favors cancer research. Despite this bias, the proportion of cancer papers on bystander genes remains low. Here, we show that the distinctive publication dynamics of cancer genes and bystander genes may be used for the identification of cancer genes. [ABSTRACT FROM AUTHOR]

Progress in DNA profiling techniques has made it possible to detect even the minimum amount of DNA at a crime scene (i.e., a complete DNA profile can be produced using as little as 100 pg of DNA, equivalent to only 15–20 human cells), leading to new defense strategies. While the evidence of a DNA trace is seldom challenged in court by a defendant's legal team, concerns are often raised about how the DNA was transferred to the location of the crime. This review aims to provide an up-to-date overview of the experimental work carried out focusing on indirect DNA transfer, analyzing each selected paper, the experimental method, the sampling technique, the extraction protocol, and the main results. Scopus and Web of Science databases were used as the search engines, including 49 papers. Based on the results of this review, one of the factors that influence secondary transfer is the amount of DNA shed by different individuals. Another factor is the type and duration of contact between individuals or objects (generally, more intimate or prolonged contact results in more DNA transfer). A third factor is the nature and quality of the DNA source. However, there are exceptions and variations depending on individual characteristics and environmental conditions. Considering that secondary transfer depends on multiple factors that interact with each other in unpredictable ways, it should be considered a complex and dynamic phenomenon that can affect forensic investigation in various ways, for example, placing a subject at a crime scene who has never been there. Correct methods and protocols are required to detect and prevent secondary transfer from compromising forensic evidence, as well as the correct interpretation through Bayesian networks. In this context, the definition of well-designed experimental studies combined with the use of new forensic techniques could improve our knowledge in this challenging field, reinforcing the value of DNA evidence in criminal trials. [ABSTRACT FROM AUTHOR]

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test ( α = 0.05 ). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis. [ABSTRACT FROM AUTHOR]

The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling. [ABSTRACT FROM AUTHOR]

Aquaculture supplies the world food market with a significant amount of valuable protein. Highly productive aquaculture fishes can be derived by utilizing genome-editing methods, and the main problem is to choose a target gene to obtain the desirable phenotype. This paper presents a review of the studies of genome editing for genes controlling body development, growth, pigmentation and sex determination in five key aquaculture Salmonidae and Cyprinidae species, such as rainbow trout (Onchorhynchus mykiss), Atlantic salmon (Salmo salar), common carp (Cyprinus carpio), goldfish (Carassius auratus), Gibel carp (Carassius gibelio) and the model fish zebrafish (Danio rerio). Among the genes studied, the most applicable for aquaculture are mstnba, pomc, and acvr2, the knockout of which leads to enhanced muscle growth; runx2b, mutants of which do not form bones in myoseptae; lepr, whose lack of function makes fish fast-growing; fads2, Δ6abc/5Mt, and Δ6bcMt, affecting the composition of fatty acids in fish meat; dnd mettl3, and wnt4a, mutants of which are sterile; and disease-susceptibility genes prmt7, gab3, gcJAM-A, and cxcr3.2. Schemes for obtaining common carp populations consisting of only large females are promising for use in aquaculture. The immobilized and uncolored zebrafish line is of interest for laboratory use. [ABSTRACT FROM AUTHOR]

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation-associated conditions (FXPAC), caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, are linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa. The issues addressed include epidemiology, clinical features, discrimination against affected persons, limited awareness and research, and poor access to resources, including genetic services and treatment programs. This paper provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of fragile X disorders. This review will improve the understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC. [ABSTRACT FROM AUTHOR]

Accurately predicting the pairing order of bases in RNA molecules is essential for anticipating RNA secondary structures. Consequently, this task holds significant importance in unveiling previously unknown biological processes. The urgent need to comprehend RNA structures has been accentuated by the unprecedented impact of the widespread COVID-19 pandemic. This paper presents a framework, Knotify_V2.0, which makes use of syntactic pattern recognition techniques in order to predict RNA structures, with a specific emphasis on tackling the demanding task of predicting H-type pseudoknots that encompass bulges and hairpins. By leveraging the expressive capabilities of a Context-Free Grammar (CFG), the suggested framework integrates the inherent benefits of CFG and makes use of minimum free energy and maximum base pairing criteria. This integration enables the effective management of this inherently ambiguous task. The main contribution of Knotify_V2.0 compared to earlier versions lies in its capacity to identify additional motifs like bulges and hairpins within the internal loops of the pseudoknot. Notably, the proposed methodology, Knotify_V2.0, demonstrates superior accuracy in predicting core stems compared to state-of-the-art frameworks. Knotify_V2.0 exhibited exceptional performance by accurately identifying both core base pairing that form the ground truth pseudoknot in 70% of the examined sequences. Furthermore, Knotify_V2.0 narrowed the performance gap with Knotty, which had demonstrated better performance than Knotify and even surpassed it in Recall and F1-score metrics. Knotify_V2.0 achieved a higher count of true positives (tp) and a significantly lower count of false negatives (fn) compared to Knotify, highlighting improvements in Prediction and Recall metrics, respectively. Consequently, Knotify_V2.0 achieved a higher F1-score than any other platform. The source code and comprehensive implementation details of Knotify_V2.0 are publicly available on GitHub. [ABSTRACT FROM AUTHOR]

Protein-DNA complex interactivity plays a crucial role in biological activities such as gene expression, modification, replication and transcription. Understanding the physiological significance of protein-DNA binding interfacial hot spots, as well as the development of computational biology, depends on the precise identification of these regions. In this paper, a hot spot prediction method called EC-PDH is proposed. First, we extracted features of these hot spots' solid solvent-accessible surface area (ASA) and secondary structure, and then the mean, variance, energy and autocorrelation function values of the first three intrinsic modal components (IMFs) of these conventional features were extracted as new features via the empirical modal decomposition algorithm (EMD). A total of 218 dimensional features were obtained. For feature selection, we used the maximum correlation minimum redundancy sequence forward selection method (mRMR-SFS) to obtain an optimal 11-dimensional-feature subset. To address the issue of data imbalance, we used the SMOTE-Tomek algorithm to balance positive and negative samples and finally used cat gradient boosting (CatBoost) to construct our hot spot prediction model for protein-DNA binding interfaces. Our method performs well on the test set, with AUC, MCC and F1 score values of 0.847, 0.543 and 0.772, respectively. After a comparative evaluation, EC-PDH outperforms the existing state-of-the-art methods in identifying hot spots. [ABSTRACT FROM AUTHOR]

The sex chromosomes of skinks are usually poorly differentiated and hardly distinguished by cytogenetic methods. Therefore, identifying sex chromosomes in species lacking easily recognizable heteromorphic sex chromosomes is necessary to fully understand sex chromosome diversity. In this paper, we employed cytogenetics, sex quantification of genes, and transcriptomic approaches to characterize the sex chromosomes in Plestiodon elegans. Cytogenetic examination of metaphases revealed a diploid number of 2n = 26, consisting of 12 macrochromosomes and 14 microchromosomes, with no significant heteromorphic chromosome pairs, speculating that the sex chromosomes may be homomorphic or poorly differentiated. The results of the sex quantification of genes showed that Calumenin (calu), COPI coat complex subunit γ 2 (copg2), and Smoothened (smo) were at half the dose in males as in females, suggesting that they are on the X chromosome. Transcriptomic data analysis from the gonads yielded the excess expression male-specific genes (n = 16), in which five PCR molecular markers were developed. Restricting the observed heterozygosity to males suggests the presence of homomorphic sex chromosomes in P. elegans, XX/XY. This is the first breakthrough in the study of the sex chromosomes of Plestiodon. [ABSTRACT FROM AUTHOR]

Advancements in the field of next generation sequencing (NGS) have generated vast amounts of data for the same set of subjects. The challenge that arises is how to combine and reconcile results from different omics studies, such as epigenome and transcriptome, to improve the classification of disease subtypes. In this study, we introduce sCClust (sparse canonical correlation analysis with clustering), a technique to combine high-dimensional omics data using sparse canonical correlation analysis (sCCA), such that the correlation between datasets is maximized. This stage is followed by clustering the integrated data in a lower-dimensional space. We apply sCClust to gene expression and DNA methylation data for three cancer genomics datasets from the Cancer Genome Atlas (TCGA) to distinguish between underlying subtypes. We evaluate the identified subtypes using Kaplan–Meier plots and hazard ratio analysis on the three types of cancer—GBM (glioblastoma multiform), lung cancer and colon cancer. Comparison with subtypes identified by both single- and multi-omics studies implies improved clinical association. We also perform pathway over-representation analysis in order to identify up-regulated and down-regulated genes as tentative drug targets. The main goal of the paper is twofold: the integration of epigenomic and transcriptomic datasets followed by elucidating subtypes in the latent space. The significance of this study lies in the enhanced categorization of cancer data, which is crucial to precision medicine. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA's high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a "hyperfibrotic" state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Tocopherols are secondary metabolites synthesized through the shikimate biosynthetic pathway in the plastids of most plants. It is well known that α–Tocopherol (vitamin E) has many health benefits for humans and animals; therefore, it is highly used in human and animal diets. Tocopherols vary considerably in most crop (and plant) species and within cultivars of the same species depending on environmental and growth conditions; tocopherol content is a polygenic, complex traits, and its inheritance is poorly understood. The objective of this review paper was to summarize all identified quantitative trait loci (QTL) that control seed tocopherols and related contents identified in maize (Zea mays) during the past two decades (2002–2022). Candidate genes identified within these QTL regions are also discussed. The QTL described here, and candidate genes identified within these genomic regions could be used in breeding programs to develop maize cultivars with high, beneficial levels of seed tocopherol contents. [ABSTRACT FROM AUTHOR]

To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory. [ABSTRACT FROM AUTHOR]

In the precision medicine era of cystic fibrosis (CF), therapeutic interventions, by the so-called modulators, target the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The levels of targetable CFTR proteins are a main variable in the success of patient-specific therapy. In turn, the CFTR protein level depends, at least in part, on the level of CFTR mRNA. Many mechanisms can modulate the CFTR mRNA level, for example, transcriptional rate, stability of the mRNA, epigenetics, and pathogenic variants that can affect mRNA production and degradation. Independently from the causes of variable CFTR mRNA levels, their exact quantitative assessment is of great importance in CF. Methods with high analytical sensitivity, precision, and accuracy are mandatory for the quantitative evaluation aimed at the amelioration of the diagnostic, prognostic, and therapeutic aspects. This paper compares, for the first time, two CFTR gene expression quantification methods: a well-established method for the relative quantification of CFTR mRNA using a real-time PCR and an innovative method for its absolute quantification using a droplet digital PCR. No comprehensive methods for absolute CFTR quantification via droplet digital PCR have been published so far. The accurate quantification of CFTR expression at the mRNA level is a critical step for the personalized therapeutic approaches of CF. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, and interactions. Further, we are only beginning to understand the role of differential regulation or function of ncRNAs caused by genetic and epigenetic perturbations, such as single nucleotide variants (SNV), deletions, insertions, and histone/DNA modifications. The 22 papers in this Special Issue describe the emerging roles of ncRNAs in neurological, cardiovascular, immune, and hepatic systems, to name a few, as well as in diseases such as cancer, Prader–Willi Syndrome, cardiac arrhythmias, and diabetes. As we begin to understand the function and regulation of this class of RNAs, strategies targeting ncRNAs could lead to improved therapeutic interventions for some conditions. [ABSTRACT FROM AUTHOR]

Gaucher disease, an autosomal recessively inherited lysosomal storage disorder, results from biallelic mutations in the GBA1 gene resulting in deficient activity of the enzyme glucocerebrosidase. In Gaucher disease, the reduced levels and activity of glucocerebrosidase lead to a disparity in the rates of formation and breakdown of glucocerebroside and glucosylsphingosine, resulting in the accumulation of these lipid substrates in the lysosome. This gives rise to the development of Gaucher cells, engorged macrophages with a characteristic wrinkled tissue paper appearance. There are both non-neuronopathic (type 1) and neuronopathic (types 2 and 3) forms of Gaucher disease, associated with varying degrees of severity. The visceral and hematologic manifestations of Gaucher disease respond well to both enzyme replacement therapy and substrate reduction therapy. However, these therapies do not improve the neuronopathic manifestations, as they cannot cross the blood–brain barrier. There is now an established precedent for treating lysosomal storage disorders with gene therapy strategies, as many have the potential to cross into the brain. The range of the gene therapies being employed is broad, but this review aimed to discuss the progress, advances, and challenges in developing viral gene therapy as a treatment for Gaucher disease. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are short, non-coding RNA segments that can be detected in a variety of clinical samples, including serum, stool, and urine. While miRNAs were initially known for their effect on post-translational gene expression, the last decade of research has shown them to be promising biomarkers for the detection of many types of cancer. This paper explores the use of miRNA detection as a tool for colorectal cancer (CRC) screening. We discuss the current state of miRNA detection, compare it to the existing CRC screening tools, and highlight the advantages and drawbacks of this approach from a clinical and logistical perspective. Our research finds that miRNA-based tests for CRC show great potential, but that widespread clinical adoption will be conditional on future research overcoming key hurdles. [ABSTRACT FROM AUTHOR]

In the rapidly advancing field of bioinformatics, the development and application of computational tools to predict the effects of single nucleotide variants (SNVs) are shedding light on the molecular mechanisms underlying disorders. Also, they hold promise for guiding therapeutic interventions and personalized medicine strategies in the future. A comprehensive understanding of the impact of SNVs in the SERPINA1 gene on alpha-1 antitrypsin (AAT) protein structure and function requires integrating bioinformatic approaches. Here, we provide a guide for clinicians to navigate through the field of computational analyses which can be applied to describe a novel genetic variant. Predicting the clinical significance of SERPINA1 variation allows clinicians to tailor treatment options for individuals with alpha-1 antitrypsin deficiency (AATD) and related conditions, ultimately improving the patient's outcome and quality of life. This paper explores the various bioinformatic methodologies and cutting-edge approaches dedicated to the assessment of molecular variants of genes and their product proteins using SERPINA1 and AAT as an example. [ABSTRACT FROM AUTHOR]

Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main symptoms associated with pathogenic variants of the ZMYND11 gene. The range of clinical manifestations of the ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present two previously unreported paediatric patients with neurodevelopmental challenges, who were diagnosed with missense variants in the ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinaemic hypoglycaemia (HH), a symptom that was not described before in published works. The reason for the occurrence of HH in our proband is not clear, so we try to explain the origin of this symptom in the context of the ZMYND11 syndrome. Thus, this paper contributes to knowledge on the range of possible manifestations of the ZMYND disease and provides further evidence supporting its association with neurodevelopmental challenges. [ABSTRACT FROM AUTHOR]

Background: Mutations in the KLHL40 gene are a common cause of severe or even lethal nemaline myopathy. Some cases with mild forms have been described, although the cases are still anecdotal. The aim of this paper was to systematically review the cases described in the literature and to describe a 12-year clinical and imaging follow-up in an Italian patient with KLHL40- related myopathy in order to suggest possible follow-up measurements. Methods: Having searched through three electronic databases (PubMed, Scopus, and EBSCO), 18 articles describing 65 patients with homozygous or compound heterozygous KLHL40 mutations were selected. A patient with a KLHL40 homozygous mutation (c.1582G>A/p.E528K) was added and clinical and genetic data were collected. Results: The most common mutation identified in our systematic review was the (c.1516A>C) followed by the (c.1582G>A). In our review, 60% percent of the patients died within the first 4 years of life. Clinical features were similar across the sample. Unfortunately, however, there is no record of the natural history data in the surviving patients. The 12-year follow-up of our patient revealed a slow improvement in her clinical course, identifying muscle MRI as the only possible marker of disease progression. Conclusions: Due to its clinical and genotype homogeneity, KLHL40-related myopathy may be a condition that would greatly benefit from the development of new gene therapies; muscle MRI could be a good biomarker to monitor disease progression. [ABSTRACT FROM AUTHOR]

Mast cell tumors are a large group of diseases occurring in dogs, cats, mice, as well as in humans. Systemic mastocytosis (SM) is a disease involving the accumulation of mast cells in organs. KIT gene mutations are very often seen in abnormal mast cells. In SM, high KIT/CD117 expression is observed; however, there are usually no KIT gene mutations present. Mastocytoma (MCT)—a form of cutaneous neoplasm—is common in animals but quite rare in humans. KIT/CD117 receptor mutations were studied as the typical changes for human mastocytosis. In 80% of human cases, the KIT gene substitution p.D816H was present. In about 25% of MCTs, metastasis was observed. Changes in the gene expression of certain genes, such as overexpression of the DNAJ3A3 gene, promote metastasis. In contrast, the SNORD93 gene blocks the expression of metastasis genes. The panel of miR-21-5p, miR-379, and miR-885 has a good efficiency in discriminating healthy and MCT-affected dogs, as well as MCT-affected dogs with and without nodal metastasis. Further studies on the pathobiology of mast cells can lead to clinical improvements, such as better MCT diagnosis and treatment. Our paper reviews studies on the topic of mast cells, which have been carried out over the past few years. [ABSTRACT FROM AUTHOR]

Kidney diseases are some of the most common healthcare problems. As the population of elderly individuals with concurrent health conditions continues to rise, there will be a heightened occurrence of these diseases. Due to the renal condition being one of the longevity predictors, early diagnosis of kidney dysfunction plays a crucial role. Currently, prevalent diagnostic tools include laboratory tests and kidney tissue biopsies. New technologies, particularly liquid biopsy and new detection biomarkers, hold promise for diagnosing kidney disorders. The aim of this review is to present modern diagnostic methods for kidney diseases. The paper focuses on the advances in diagnosing three common renal disorders: diabetic kidney disease, renal cancer, and immunoglobulin A nephropathy. We highlight the significance of liquid biopsy and epigenetic changes, such as DNA methylation, microRNA, piRNAs, and lncRNAs expression, or single-cell transcriptome sequencing in the assessment of kidney diseases. This review underscores the importance of early diagnosis for the effective management of kidney diseases and investigates liquid biopsy as a promising approach. [ABSTRACT FROM AUTHOR]

DNA methylation is critically involved in the regulation of chromatin states and cell-type-specific gene expression. The exclusive expression of imprinted genes from either the maternal or the paternal allele is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). Aberrant DNA hyper- or hypomethylation at the ICR1 of the H19/IGF2 imprinting locus is characteristic for the imprinting disorders Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS), respectively. In this paper, we performed epigenome editing to induce targeted DNA demethylation at ICR1 in HEK293 cells using dCas9-SunTag and the catalytic domain of TET1. 5-methylcytosine (5mC) levels at the target locus were reduced up to 90% and, 27 days after transient transfection, >60% demethylation was still observed. Consistent with the stable demethylation of CTCF-binding sites within the ICR1, the occupancy of the DNA methylation-sensitive insulator CTCF protein increased by >2-fold throughout the 27 days. Additionally, the H19 expression was increased by 2-fold stably, while IGF2 was repressed though only transiently. Our data illustrate the ability of epigenome editing to implement long-term changes in DNA methylation at imprinting control regions after a single transient treatment, potentially paving the way for therapeutic epigenome editing approaches in the treatment of imprinting disorders. [ABSTRACT FROM AUTHOR]

Biological data at the omics level are highly complex, requiring powerful computational approaches to identifying significant intrinsic characteristics to further search for informative markers involved in the studied phenotype. In this paper, we propose a novel dimension reduction technique, protein–protein interaction-based gene correlation filtration (PPIGCF), which builds on gene ontology (GO) and protein–protein interaction (PPI) structures to analyze microarray gene expression data. PPIGCF first extracts the gene symbols with their expression from the experimental dataset, and then, classifies them based on GO biological process (BP) and cellular component (CC) annotations. Every classification group inherits all the information on its CCs, corresponding to the BPs, to establish a PPI network. Then, the gene correlation filter (regarding gene rank and the proposed correlation coefficient) is computed on every network and eradicates a few weakly correlated genes connected with their corresponding networks. PPIGCF finds the information content (IC) of the other genes related to the PPI network and takes only the genes with the highest IC values. The satisfactory results of PPIGCF are used to prioritize significant genes. We performed a comparison with current methods to demonstrate our technique's efficiency. From the experiment, it can be concluded that PPIGCF needs fewer genes to reach reasonable accuracy (~99%) for cancer classification. This paper reduces the computational complexity and enhances the time complexity of biomarker discovery from datasets. [ABSTRACT FROM AUTHOR]

Early childhood caries (ECC) is a disease that globally affects pre-school children. It is important to identify both protective and risk factors associated with this disease. This paper examined a set of saliva samples of Thai mother–child dyads and aimed to analyze how the maternal factors and oral microbiome of the dyads influence the development of ECC. However, heterogeneous latent subpopulations may exist that have different characteristics in terms of caries development. Therefore, we introduce a novel method to cluster the correlated outcomes of dependent observations while selecting influential independent variables to unearth latent groupings within this dataset and reveal their association in each group. This paper describes the discovery of three heterogeneous clusters in the dataset, each with its own unique mother–child outcome trend, as well as identifying several microbial factors that contribute to ECC. Significantly, the three identified clusters represent three typical clinical conditions in which mother–child dyads have typical (cluster 1), high–low (cluster 2), and low–high caries experiences (cluster 3) compared to the overall trend of mother–child caries status. Intriguingly, the variables identified as the driving attributes of each cluster, including specific taxa, have the potential to be used in the future as caries preventive measures. [ABSTRACT FROM AUTHOR]

The underlying pathology is atheromatous vascular disease, resulting in coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease, in addition to the subsequent development of heart failure, cardiac arrhythmias, and other related disorders [[1]]. Cardiovascular and cerebrovascular diseases are the leading causes of the mortality of humans in the 21st century. This Special Issue contains seven original research articles and two review papers that further our collective knowledge of the etiology of cardiovascular and cerebrovascular diseases, as well as the genetic and modifiable risk factors underlying the diseases. [Extracted from the article]

Bacteriophage λ's CI repressor protein controls a genetic switch between the virus's lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites. We further revealed direct readout information shared among three evolutionarily related lambdoid phages: λ-phage, Enterobacteria phage VT2-Sakai, and Stx2 converting phage I, suggesting that the λ-CI protein could bind to the operator sites of these other phages. In this study, we show that λ-CI can indeed bind the other two phages' cognate binding sites as predicted using our algorithm, validating the hypotheses from that paper. We go on to demonstrate the importance of specific hydrogen bond donors and acceptors that are maintained despite changes to the nucleobase itself, and another that has an important role in recognition and binding. This in vitro validation of our algorithm supports its use as a tool to predict alternative binding sites for DNA-binding proteins. [ABSTRACT FROM AUTHOR]

Allergy to shellfishes, including mollusks and crustaceans, is a growing health concern worldwide. Crustacean shellfish is one of the "Big Eight" allergens designated by the U.S. Food and Drug Administration and is the major cause of food-induced anaphylaxis. Shrimp is one of the most consumed crustaceans triggering immunoglobulin E (IgE)-mediated allergic reactions. Over the past decades, the allergen repertoire of shrimp has been unveiled based on conventional immunodetection methods. With the availability of genomic data for penaeid shrimp and other technological advancements like transcriptomic approaches, new shrimp allergens have been identified and directed new insights into their expression levels, cross-reactivity, and functional impact. In this review paper, we summarize the current knowledge on shrimp allergens, as well as allergens from other crustaceans and mollusks. Specific emphasis is put on the genomic information of the shrimp allergens, their protein characteristics, and cross-reactivity among shrimp and other organisms. [ABSTRACT FROM AUTHOR]

PIK3CA-related disorders encompass many rare and ultra-rare conditions caused by somatic genetic variants that hyperactivate the PI3K-AKT-mTOR signaling pathway, which is essential for cell cycle control. PIK3CA-related disorders include PIK3CA-related overgrowth spectrum (PROS), PIK3CA-related vascular malformations and PIK3CA-related non-vascular lesions. Phenotypes are extremely heterogeneous and overlapping. Therefore, diagnosis and management frequently involve various health specialists. Given the rarity of these disorders and the limited number of centers offering optimal care, the Scientific Committee of the Italian Macrodactyly and PROS Association has proposed a revision of the most recent recommendations for the diagnosis, molecular testing, clinical management, follow-up, and treatment strategies. These recommendations give insight on molecular diagnosis, eligible samples, preferable sequencing, and validation methods and management of negative results. The purpose of this paper is to promote collaboration between health care centers and clinicians with a joint shared approach. Finally, we suggest the direction of present and future research studies, including new systemic target therapies, which are currently under evaluation in several clinical trials, such as specific inhibitors that can be employed to downregulate the signaling pathway. [ABSTRACT FROM AUTHOR]

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important food, feed, industrial raw materials, and new energy crops, and is widely cultivated around the world. China is the largest sweet potato producer in the world, and the sweet potato industry plays an important role in China's agriculture. During the growth of sweet potato, it is often affected by biotic stresses, such as fungi, nematodes, insects, viruses, and bacteria. These stressors are widespread worldwide and have severely restricted the production of sweet potato. In recent years, with the rapid development and maturity of biotechnology, an increasing number of stress-related genes have been introduced into sweet potato, which improves its quality and resistance of sweet potato. This paper summarizes the discovery of biological stress-related genes in sweet potato and the related mechanisms of stress resistance from the perspectives of genomics analysis, transcriptomics analysis, genetic engineering, and physiological and biochemical indicators. The mechanisms of stress resistance provide a reference for analyzing the molecular breeding of disease resistance mechanisms and biotic stress resistance in sweet potato. [ABSTRACT FROM AUTHOR]

Mutations in the 43 kDa transactive-response (TAR)-DNA-binding protein (TARDBP) are associated with 2–5% of familial Amyotrophic Lateral Sclerosis (ALS) cases. TAR DNA-Binding Protein 43 (TDP-43) is an RNA/DNA-binding protein involved in several cellular mechanisms (e.g., transcription, pre-mRNA processing, and splicing). Many ALS-linked TARDBP mutations have been described in the literature, but few phenotypic data on monogenic TARDBP-mutated ALS are available. In this paper, (1) we describe the clinical features of ALS patients carrying mutations in the TARDBP gene evaluated at the Tertiary ALS Center at Maggiore della Carità University Hospital, Novara, Italy, from 2010 to 2020 and (2) present the results of our review of the literature on this topic, analyzing data obtained for 267 patients and highlighting their main clinical and demographic features. [ABSTRACT FROM AUTHOR]