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Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic–clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development. [ABSTRACT FROM AUTHOR]

The diverse climatic and geological history of Southeast Asia has been a driving force behind significant Pleistocene and Holocene range dynamics and the consequent biological diversification in the region. Among the species exhibiting wide distributions, extending across several well-known zoogeographic barriers, the Elongated Tortoise (Indotestudo elongata) is noted for its extensive variability in size, shape, and colouration. To examine phylogeographic differentiation within I. elongata, we analysed three mitochondrial gene fragments (ND4, cyt b, and COI) for 52 individuals including fourteen historic specimens and 25 sequences obtained from Gen- Bank. Phylogenetic analyses of the concatenated alignment revealed genetic homogeneity across the range, supported by a shallow mean uncorrected p distance of 1.2% in cyt b. This corresponds to a surprising lack of biogeographic structuring. Concordantly, multivariate statistical analyses of morphometric and colouration-related characters of 166 adult tortoises (79 males and 87 females) from Myanmar, Thailand, Cambodia, and Vietnam showed no statistically significant differences between biogeographic units. The lack of any phylogeographic signal and morphological differentiation despite the presence of significant biogeographic barriers is unusual for a terrestrial vertebrate from this region. Archaeological evidence suggests that Elongated Tortoises have been used as a food item for millennia. It could be that their current wide distribution and the absence of genetic differentiation are the result of a significant range expansion caused by extensive human-mediated dispersal over the prehistoric and historic tortoise trade. The observed lack of phylogeographic structure considerably simplifies conservation measures such as conservation breeding, reintroduction, and population reinforcement. [ABSTRACT FROM AUTHOR]

Summary: Rice tillering is one of the most important agronomical traits largely determining grain yield. Photosynthesis and nitrogen availability are two important factors affecting rice tiller bud elongation; however, underlying mechanism and their cross‐talk is poorly understood.Here, we used map‐based cloning, transcriptome profiling, phenotypic analysis, and molecular genetics to understand the roles of the Decreased Tiller Number 1 (DTN1) gene that encodes the fructose‐1,6‐bisphosphate aldolase and involves in photosynthesis required for light‐induced axillary bud elongation in rice.Deficiency of DTN1 results in the reduced photosynthetic rate and decreased contents of sucrose and other sugars in both leaves and axillary buds, and the reduced tiller number in dtn1 mutant could be partially rescued by exogenous sucrose treatment. Furthermore, we found that the expression of nitrogen‐mediated tiller growth response 5 (NGR5) was remarkably decreased in shoot base of dtn1‐2, which can be activated by sucrose treatment. Overexpression of NGR5 in the dtn1‐2 could partially rescue the reduced tiller number, and the tiller number of dtn1‐2 was insensitive to nitrogen supply.This work demonstrated that the sugar level regulated by photosynthesis and DTN1 could positively regulate NGR5 expression, which coordinates the cross‐talk between carbon and nitrate to control tiller bud outgrowth in rice. [ABSTRACT FROM AUTHOR]

SUMMARY Maintaining an optimal redox status is essential for plant growth and development, particularly when the plants are under stress. AT‐hook motif nuclear localized (AHL) proteins are evolutionarily conserved transcription factors in plants. Much of our understanding about this gene family has been derived from studies on clade A members. To elucidate the functions of clade B genes, we first analyzed their spatial expression patterns using transgenic plants expressing a nuclear localized GFP under the control of their promoter sequences. AHL1, 2, 6, 7, and 10 were further functionally characterized owing to their high expression in the root apical meristem. Through mutant analyses and transgenic studies, we showed that these genes have the ability to promote root growth. Using yeast one‐hybrid and dual luciferase assays, we demonstrated that AHL1, 2, 6, 7, and 10 are transcription regulators and this activity is required for their roles in root growth. Although mutants for these genes did not showed obvious defects in root growth, transgenic plants expressing their fusion proteins with the SRDX repressor motif exhibited a short‐root phenotype. Through transcriptome analysis, histochemical staining and molecular genetics experiments, we found that AHL10 maintains redox homeostasis via direct regulation of glutathione transferase (GST) genes. When the transcript level of GSTF2, a top‐ranked target of AHL10, was reduced by RNAi, the short‐root phenotype in the AHL10‐SRDX expressing plant was largely rescued. These results together suggest that AHL genes function redundantly in promoting root growth through direct regulation of redox homeostasis. [ABSTRACT FROM AUTHOR]

Background: A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. Methods: Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. Results: Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. Conclusions: The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) platforms have emerged as pivotal tools in genetics and molecular medicine, as in many other fields. The growth in patient data, identification of new diseases and phenotypes, discovery of new intracellular pathways, availability of greater sets of omics data, and the need to continuously analyse them have led to the development of new AI platforms. AI continues to weave its way into the fabric of genetics with the potential to unlock new discoveries and enhance patient care. This technology is setting the stage for breakthroughs across various domains, including dysmorphology, rare hereditary diseases, cancers, clinical microbiomics, the investigation of zoonotic diseases, omics studies in all medical disciplines. AI’s role in facilitating a deeper understanding of these areas heralds a new era of personalised medicine, where treatments and diagnoses are tailored to the individual’s molecular features, offering a more precise approach to combating genetic or acquired disorders. The significance of these AI platforms is growing as they assist healthcare professionals in the diagnostic and treatment processes, marking a pivotal shift towards more informed, efficient, and effective medical practice. In this review, we will explore the range of AI tools available and show how they have become vital in various sectors of genomic research supporting clinical decisions. [ABSTRACT FROM AUTHOR]

Background: Nucleophosmin 1 (NPM1) gene‐mutated acute myeloid leukemia (NPM1mut AML) is classified as a subtype with a favorable prognosis. However, some patients fail to achieve a complete remission or relapse after intensified chemotherapy. Genetic abnormalities in concomitant mutations contribute to heterogeneous prognosis of NPM1mut AML patients. Methods: In this study, 91 NPM1‐mutated and FLT3‐ITD wild‐type (NPM1mut/FLT3‐ITDwt) AML patients with intermediate‐risk karyotype were enrolled to analyze the impact of common genetic co‐mutations on chemotherapeutic outcome. Results: Our data revealed that TET1/2 (52/91, 57.1%) was the most prevalent co‐mutation in NPM1mut AML patients, followed by IDH1/2 (36/91, 39.6%), DNMT3A (35/91, 38.5%), myelodysplastic syndrome related genes (MDS‐related genes) (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 genes) (35/91, 38.5%), FLT3‐TKD (27/91, 29.7%) and GATA2 (13/91, 14.3%) mutations. Patients with TET1/2mut exhibited significantly worse relapse‐free survival (RFS) (median, 28.7 vs. not reached (NR) months; p = 0.0382) compared to patients with TET1/2wt, while no significant difference was observed in overall survival (OS) (median, NR vs. NR; p = 0.3035). GATA2mut subtype was associated with inferior OS (median, 28 vs. NR months; p < 0.0010) and RFS (median, 24 vs. NR months; p = 0.0224) compared to GATA2wt. By multivariate analysis, GATA2mut and MDS‐related genesmut were independently associated with worse survival. Conclusion: Mutations in TET1/2, GATA2 and MDS‐related genes were found to significantly influence the chemotherapeutic outcome of patients with NPM1mut AML. The findings of our study have significant clinical implications for identifying patients who have an adverse response to frontline chemotherapy and provide a novel reference for further prognostic stratification of NPM1mut/FLT3‐ITDwt AML patients. [ABSTRACT FROM AUTHOR]

This article is a letter to the editor in response to a recent paper on the genetic analysis of ancient Patagonians. The authors respectfully disagree with the conclusions of the previous study, specifically regarding the genetic connections with other South American regions. They argue that the phylogenetic analysis does not support the claimed affiliations with Peruvian populations and propose an alternative explanation for the genetic patterns observed. The authors also express their preference for using median-joining networks in phylogenetic analysis. [Extracted from the article]

Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription‐factor‐related forms, and syndromic forms. The widespread use of next‐generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic‐specific role of the SEC23B loss‐of‐function in iron metabolism dysregulation in CDA II, deepening CDIN1 dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with RACGAP1 variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics. [ABSTRACT FROM AUTHOR]

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The relative biological effectiveness is a mathematical quantity first defined in the 1950s. This has resulted in more than 4,000 scientific papers published to date. Yet defining the correct value of the RBE to use in clinical practice remains a challenge. A scientific analysis in the radiation research literature can provide an understanding of how this mathematical quantity has evolved. The purpose of this study is to investigate documents published since 1950 using bibliometric indicators and network visualization. This analysis seeks to provide an assessment of global research activities, key themes, and RBE research within the radiation-related field. It strives to highlight top-performing authors, organizations, and nations that have made major contributions to this research domain, as well as their interactions. The Scopus Collection was searched for articles and reviews pertaining to RBE in radiation research from 1950 through 2023. Scopus and Bibiometrix analytic tools were used to investigate the most productive countries, researchers, collaboration networks, journals, along with the citation analysis of references and keywords. A total of 4,632 documents were retrieved produced by authors originating from 71 countries. Publication trends could be separated in 20-year groupings beginning with slow accrual from 1950 to 1970, an early rise from 1970-1990, followed by a sharp increase in the years 1990s-2010s that matches the development of charged particle therapy in clinics worldwide and opened discussion on the true value of the RBE in proton beam therapy. Since the 2010s, a steady 200 papers, on average, have been published per year. The United States produced the most publications overall (N = 1,378) and Radiation Research was the most likely journal to have published articles related to the RBE (606 publications during this period). J. Debus was the most prolific author (112 contributions, with 2,900 citations). The RBE has captured the research interest of over 7,000 authors in the past decade alone. This study supports that notion that the growth of the body of evidence surrounding the RBE, which started 75 years ago, is far from reaching its end. Applications to medicine have continuously dominated the field, with physics competing with Biochemistry, Genetics and Molecular Biology for second place over the decades. Future research can be predicted to continue. [ABSTRACT FROM AUTHOR]

Climate deterioration, water shortages, and abiotic stress are the main threats worldwide that seriously affect cotton growth, yield, and fiber quality. Therefore, research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance. The NAC proteins are crucial and plant-specific transcription factors (TFs) that are involved in cotton growth, development, and stress responses. The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible. Based on cotton genomic data, genome-wide identification and analyses have revealed potential functions of cotton NAC genes. Here, we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought, salt, and Verticillium wilt-related stresses, as well as leaf senescence and the development of fibers, xylem, and glands. The detailed regulatory network of NAC proteins in cotton is also elucidated. Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation, participate in several biological processes by interacting with related proteins, and regulate the expression of downstream genes. Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance. This review elucidates the latest findings on the functions and regulation of cotton NAC proteins, broadens our understanding of cotton NAC TFs, and lays a fundamental foundation for further molecular breeding research in cotton. [ABSTRACT FROM AUTHOR]

In the 1990s, as prevention became a central strategy in the battle against cancer and the molecular genetics revolution uncovered the genetic basis of numerous hereditary cancer syndromes, there were no options available for patients at increased risk of developing pancreatic cancer. When surveillance efforts for those at familial and hereditary risk of pancreatic cancer emerged in the late 1990s, it was uncertain if early detection was achievable. In this introduction to the special issue, we offer an overview of the history of surveillance for pancreatic cancer, including the first reports of familial pancreatic cancer in the medical literature, the initial results of surveillance in the United States and the initiation of surveillance programs for hereditary pancreatic cancer in the Netherlands. This special issue features a collection of 18 articles written by prominent experts in the field, focusing specifically on refining surveillance methodologies with the primary objective of improving care of high-risk individuals. Several reviews in this collection highlight improved survival rates associated with pancreas surveillance, underlying the potential of early detection and improved management in the continuing fight against pancreatic cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the prevalence of likely pathogenic or pathogenic variants and assess the diagnostic yield from genetic testing for cardiac arrhythmias in Norway since 2003. Data from 1991 probands and 2782 relatives were retrospectively collected from the laboratory information management system at Unit for Cardiac and Cardiovascular Genetics, Oslo University hospital. Of 1991 probands, 57.4% were females, age at genetic testing was 33.1 (±22.7) years, and 32.5% were under the age of 18. A likely pathogenic or pathogenic variant (including 14 novel) was detected in 15.4% in total. Of the 2782 relatives, 53.7% were females, age at genetic testing was 35.6 (±22.5) years, 27.3% were under the age of 18, and 45.3% carried the family variant. Probands and relatives combined, 1/3356 persons in the Norwegian population were heterozygous for an arrhythmia‐causing variant. The founder variant p.Q530X (NM_000218.2: c.1588C>T) in KCNQ1 accounted for 34% of all variants in Norway. In conclusion, genetic testing provided a genetic basis of the arrhythmia in 15.4% of the probands. Familial cascade screening identified four times as many variant‐positive relatives, allowing early detection and prompt stratification of arrhythmic risk of those variant carriers. [ABSTRACT FROM AUTHOR]

AbstractNear-tetraploidy/tetraploidy (NT/T) is a cytogenetic alteration in acute myeloid leukemia (AML). In AML, specific chromosomal alterations are associated with clinical, morphological, and immunophenotypic features. The impact of cytogenetics on the prognosis of AML is well established. However, the prognostic implication of NT/T on AML remains unclear. Our aim is to further characterize the clinical, morphologic, immunophenotypic, molecular mutational, and prognostic features of NT/T AML. This retrospective chart review of NT/T AML cases showed NT/T AML was more common in older adult males, with predominately large blasts and myelodysplasia-related features. The most common lineage of dysplasia was dysgranulopoiesis in 77.8% of cases. Cases displayed multiple cytogenetic abnormalities, with only four showing NT/T as the sole abnormality. TP53 was the most common molecular mutation associated with NT/T AML (44.5%). Of the patients receiving treatment for NT/T AML, 80% achieved a CR. The median overall survival for the entire cohort was 4.5 months. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS). Methods: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years). Results: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences. Conclusion: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of extraocular muscles (EOMs) in the strabismus may be partly due to modification in the mitochondrial DNA (mtDNA). Currently, little is known about changes occurring in mtDNA of EOMs in patients with strabismus, therefore the aim of our study was to analyze if there are any changes occurring in the mitochondrial DNA of extraocular muscles in children that underwent strabismus surgery in our clinic. Methods: MtDNA was isolated from the tissue material using the Qiagen kit. Assessment of mtDNA mutations was performed by next-generation sequencing (NGS) using the Illumina MiSeq protocol. Results: The examination revealed the presence of atrophic changes in muscle fibers. NGS evaluation revealed a dominant genetic mutation in the ANT1 gene in 12 of the 15 patients examined. Conclusions: The presented results constitute the beginning of research on changes in mtDNA occurring in the muscles of children with strabismus surgery. Further studies are necessary in the context of resolving the transcriptomic differences between strabismic and non-strabismic EOMs. Better understanding of the molecular genetics of strabismus will lead to improved knowledge of the disease mechanisms and ultimately to a more effective treatment. [ABSTRACT FROM AUTHOR]

SUMMARY: A fundamental question in developmental biology is how to regulate grain size to improve crop yields. Despite this, little is still known about the genetics and molecular mechanisms regulating grain size in crops. Here, we provide evidence that a putative protein kinase‐like (OsLCD3) interacts with the S‐adenosyl‐L‐methionine synthetase 1 (OsSAMS1) and determines the size and weight of grains. OsLCD3 mutation (lcd3) significantly increased grain size and weight by promoting cell expansion in spikelet hull, whereas its overexpression caused negative effects, suggesting that grain size was negatively regulated by OsLCD3. Importantly, lcd3 and OsSAMS1 overexpression (SAM1OE) led to large and heavy grains, with increased ethylene and decreased polyamines production. Based on genetic analyses, it appears that OsLCD3 and OsSAMS1 control rice grain size in part by ethylene/polyamine homeostasis. The results of this study provide a genetic and molecular understanding of how the OsLCD3‐OsSAMS1 regulatory module regulates grain size, suggesting that ethylene/polyamine homeostasis is an appropriate target for improving grain size and weight. Significance Statement: The results of this study provide a genetic and molecular understanding of how the OsLCD3‐OsSAMS1 regulatory module regulates grain size, suggesting that ethylene/polyamine homeostasis is an appropriate target for improving grain size and weight. [ABSTRACT FROM AUTHOR]

Background: There is considerable global discourse on the impact of insufficient vitamin D levels, known for their immunosuppressive properties, on recurrent pregnancy loss. Vitamin D deficiency affects 35% to 80% of the population. Despite advancements in molecular genetics, the study of vitamin D receptor gene (VDR) polymorphisms remains crucial. This study examined the correlation between VDR polymorphisms and idiopathic recurrent pregnancy loss. Methods: A narrative literature review with a meta-analysis of 85 sources from databases such as PubMed, Web of Science, and Scopus was conducted, focusing on studies from 2020 to 2022. The analysis included studies on vitamin D and miscarriage, adhering to ICD-10 criteria, and VDR gene allele analysis through PCR-RFLP. Results: A comprehensive narrative analysis of the available scientific literature verified the link between comorbidities and vitamin D deficiencies, which can lead to recurrent pregnancy loss by hindering adaptive mechanisms and exacerbating complications. Conclusion: The most researched VDR gene polymorphisms, including FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and Cdx2, are linked to various health issues, particularly reproductive outcomes. The FokI (rs2228570) polymorphism in the VDR gene is a critical predictor of vitamin D levels, influencing pregnancy success. These findings are essential for assessing the risk of idiopathic recurrent pregnancy loss and developing new prevention and treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. Methods: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. Results: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. Conclusions: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China. [ABSTRACT FROM AUTHOR]

Developmental biology—the study of the processes by which cells, tissues, and organisms develop and change over time—has entered a new golden age. After the molecular genetics revolution in the 80s and 90s and the diversification of the field in the early 21st century, we have entered a phase when powerful technologies provide new approaches and open unexplored avenues. Progress in the field has been accelerated by advances in genomics, imaging, engineering, and computational biology and by emerging model systems ranging from tardigrades to organoids. We summarize how revolutionary technologies have led to remarkable progress in understanding animal development. We describe how classic questions in gene regulation, pattern formation, morphogenesis, organogenesis, and stem cell biology are being revisited. We discuss the connections of development with evolution, self-organization, metabolism, time, and ecology. We speculate how developmental biology might evolve in an era of synthetic biology, artificial intelligence, and human engineering. As developmental biology enters a new golden age, this Review summarizes how revolutionary technologies have been integral to the advancement of the field over the last five decades and speculates on how developmental biology might evolve with the changing landscape of cutting-edge technology. [ABSTRACT FROM AUTHOR]

Despite considerable progress has been made in the understanding of the genetics and molecular biology of renal cell carcinoma (RCC), therapeutic options of patients with papillary renal cell carcinoma (PRCC) are limited. Immunotherapy based on immune checkpoint inhibitors (ICIs) has become a hot point in researching new drug for tumor and been tested in a number of human clinical trials. In this study, an immune-related gene prognostic index (IRGPI) was developed and provided a comprehensive and systematic analysis of distinct phenotypic and molecular portraits in the recognition, surveillance, and prognosis of PRCC. The reliability of the IRGPI was evaluated using independent datasets from GEO database and the expression levels of the genes in the IRGPI detected by real-time PCR. Collectively, the currently established IRGPI could be used as a potential biomarker to evaluate the response and efficacy of immunotherapy in PRCC. [ABSTRACT FROM AUTHOR]

Background: Atypical chronic myeloid leukemia (aCML) is a highly aggressive type of blood cancer that falls under the category of myelodysplastic/myeloproliferative neoplasms (MDS/MPN). In the fifth edition of the WHO classification of tumors, this category has been renamed MDS/MPN with neutrophilia. Although eosinophilia is commonly observed in blood cancers, it is rarely seen in aCML. Case presentation: This study presents a case of aCML that was diagnosed six years after the patient developed eosinophilia. The patient had undergone tests to rule out other primary and secondary diseases, but the eosinophilia remained unexplained. Treatment with corticosteroids and hydroxyurea had proven ineffective. Six years later, the patient experienced an increase in white blood cells, primarily neutrophils. After ruling out other possible diagnoses, a combination of morphologic and molecular genetic findings led to the diagnosis of aCML. The patient responded well to treatment with azacitidine. Conclusions: This study summarizes the current state of aCML diagnosis and management and discusses the possible connection between eosinophilia and aCML. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Discussion Neonatal diabetes mellitus (NDM) is a rare non‐immunological monogenic disorder characterized by hyperglycemic conditions primarily occurring within the first 6 months of life. The majority of cases are attributed to pathogenic variants in genes affecting beta‐cell survival, insulin regulation, and secretion. This study aims to investigate the genetic landscape of NDM in Iran.We recruited a total of 135 patients who were initially diagnosed with diabetes at <12 months of age in Iran and referred to pediatric endocrinology clinics across the country. These patients underwent genetic diagnostic tests conducted by the Exeter Molecular Genetics Laboratory in the UK. The pathogenic variants identified were sorted and described based on type, pathogenicity (according to ACMG/AMP criteria), novelty, and the affected protein domain.Genetic defects were identified in 93 probands, presenting various pathogenic abnormalities associated with NDM and its associated syndromes. 76% of the patients were born as a result of consanguineous marriage, and a familial history of diabetes was found in 43% of the cases. A total of 58 distinct variants in 14 different genes were discovered, including 20 variants reported for the first time. Causative variants were most frequently identified in EIF2AK3, KCNJ11, and ABCC8, respectively. Notably, EIF2AK3 and ABCC8 exhibited the highest number of novel variants.These findings provide valuable insights into the genetic landscape of NDM in the Iranian population and contribute to the knowledge of novel pathogenic variants within known causative genes. [ABSTRACT FROM AUTHOR]

This article highlights the significance of understanding the genetic factors involved in rheumatologic autoimmune diseases (RADs) to enhance patient outcomes. The Clinical Genome Resource (ClinGen) is a consortium that collects and verifies genomic data to ensure the accuracy of genetic tests. The article emphasizes the need for commercial testing panels to include valid and clinically relevant genetic variants. The ClinGen Rheumatologic Autoimmune Disease Clinical Domain Working Group (RAD CDWG) has been established to curate genetic associations with RADs, focusing on both monogenic and complex diseases. The group will evaluate the strength of evidence supporting gene-disease associations and curate variants associated with specific diseases. The curated information will be publicly accessible on the ClinGen website. The ClinGen RAD Clinical Domain Working Group is dedicated to comprehending the genetic basis of RADs. They aim to develop frameworks and methodologies for curating genetic associations, including variants of unknown significance and complex, multigenic diseases. The group also recognizes the importance of curating disease-associated somatic variants in conditions like cancer and aging. Their efforts aim to enhance the diagnosis, treatment, and prevention strategies for RADs and contribute to the field of genomic medicine in rheumatology. [Extracted from the article]

Background: Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma, characterized by abnormal B-cell growth within the germinal center. Research has shown the role of genes and molecular pathways in the pathogenesis of FL. However, the main factor of pathogenesis has not been determined. Therefore, in this study, the genes and molecular pathways related to the pathogenesis of FL were evaluated using a systems biology approach. Materials and Methods: In this study (bioinformatics analysis), the GSE32018 database was used for data analysis. This database was extracted from Gene Expression Omnibus (GEO). The sample of this database was 36, which included normal and FL samples. For this purpose, 23 cases were FL and 13 were healthy samples. Protein-protein interaction (PPI) is performed to show the interaction between DEGs. STRING software is used for this purpose. Associations between the hub genes, transcription factors, and microRNAs were assessed using the miRTarBase and TRRUST databases. The criteria used for data analysis included log fold change greater than one and p < 0.05. Results: After evaluating and analyzing the data, the results showed that 866 DEGs were identified between the control and FL samples. Of this population, 231 cases of UP regulation and 635 cases of downregulation were in FL samples compared to control samples. PPI network and hub gene analyses identified 7 hub genes, including RPL37A, MRPS7, RPS14, RPS28, RPL34, RPS20, and RPS3. According to the results, hsa-miR-191-5p has the highest interactions with hub genes among miRNAs, and KDM5A has the most interactions among TFs. Conclusion: Identifying genes and molecular pathways can be effective in designing therapeutic strategies and preventing the proliferation of FL cells, thereby increasing patients' survival. [ABSTRACT FROM AUTHOR]

Bos taurus is known for its tolerance of coarse grains, adaptability, high temperature, humidity, and disease resistance. Primarily, cattle are raised for their meat and milk, and pinpointing genes associated with traits relevant to meat production can enhance their overall productivity. The aim of this study was to identify the genome, analyze the evolution, and explore the function of the Pax gene family in B. taurus to provide a new molecular target for breeding in meat-quality-trait cattle. In this study, 44 Pax genes were identified from the genome database of five species using bioinformatics technology, indicating that the genetic relationships of bovids were similar. The Pax3 and Pax7 protein sequences of the five animals were highly consistent. In general, the Pax gene of the buffalo corresponds to the domestic cattle. In summary, there are differences in affinity between the Pax family genes of buffalo and domestic cattle in the Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6 subfamilies. We believe that Pax1/9 has an effect on the growth traits of buffalo and domestic cattle. The Pax3/7 gene is conserved in the evolution of buffalo and domestic animals and may be a key gene regulating the growth of B. taurus. The Pax2/5/8 subfamily affects coat color, reproductive performance, and milk production performance in cattle. The Pax4/6 subfamily had an effect on the milk fat percentage of B. taurus. The results provide a theoretical basis for understanding the evolutionary, structural, and functional characteristics of the Pax family members of B. taurus and for molecular genetics and the breeding of meat-production B. taurus species. [ABSTRACT FROM AUTHOR]

Cucumber is an important member of Cucurbitaceae family which is grown and consumed globally. It is consumed in the form of salads or pickles and has abundant supply of minerals and vitamins. It has been a focus of extensive research due to its publically available genome sequences. Marker assisted breeding has been employed to generate improved varieties of cucumber with resistance to various diseases besides desirable horticultural traits. One such trait is the production of parthenocarpic fruits i.e. seedless fruits developed in the absence of pollination. Naturally, parthenocarpy occurs under unfavourable environmental conditions. However, it is possible to artificially induce parthenocarpy by applying plant growth regulators. At molecular level, parthenocarpy is a result of complex role-play of genes and hormones with tight regulation. Many researchers aim at developing parthenocarpic varieties by either transferring the trait into existing varieties with resistance to specific diseases or by knocking off genes controlling parthenocarpy. A comprehensive knowledge of background and genetics of parthenocarpy is required in both cases. This review includes an-inclusive study of the molecular basis of parthenocarpy. The genes and hormones involved and their functions, inheritance of parthenocarpy and markers associated with it have been given in detail. [ABSTRACT FROM AUTHOR]

The application of dyes to understanding the aetiology of infection inspired antimicrobial chemotherapy and the first wave of antibacterial drugs. The second wave of antibacterial drug discovery was driven by rapid discovery of natural products, now making up 69% of current antibacterial drugs. But now with the most prevalent natural products already discovered, ∼107 new soil-dwelling bacterial species must be screened to discover one new class of natural product. Therefore, instead of a third wave of antibacterial drug discovery, there is now a discovery bottleneck. Unlike natural products which are curated by billions of years of microbial antagonism, the vast synthetic chemical space still requires artificial curation through the therapeutics science of antibacterial drugs — a systematic understanding of how small molecules interact with bacterial physiology, effect desired phenotypes, and benefit the host. Bacterial molecular genetics can elucidate pathogen biology relevant to therapeutics development, but it can also be applied directly to understanding mechanisms and liabilities of new chemical agents with new mechanisms of action. Therefore, the next phase of antibacterial drug discovery could be enabled by integrating chemical expertise with systematic dissection of bacterial infection biology. Facing the ambitious endeavour to find new molecules from nature or new-to-nature which cure bacterial infections, the capabilities furnished by modern chemical biology and molecular genetics can be applied to prospecting for chemical modulators of new targets which circumvent prevalent resistance mechanisms. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) are most prevalent cardiac defects that occur at birth, leading to significant neonatal mortality and morbidity, especially in the developing nations. Among the CHDs, conotruncal heart defects (CTDs) are particularly noteworthy, comprising a significant portion of congenital cardiac anomalies. While advances in imaging and surgical techniques have improved the diagnosis, prognosis, and management of CTDs, their molecular genetics and genomic substrates remain incompletely understood. This expert review covers the recent advances from January 2016 onward and examines the complexities surrounding the genetic etiologies, prevalence, embryology, diagnosis, and clinical management of CTDs. We also emphasize the known copy number variants and single nucleotide variants associated with CTDs, along with the current planetary health research efforts aimed at CTDs in large cohort studies. In all, this comprehensive narrative review of molecular genetics and genomics research and innovation on CTDs draws from and highlights selected works from around the world and offers new ideas for advances in CTD diagnosis, precision medicine interventions, and accurate assessment of prognosis and recurrence risks. [ABSTRACT FROM AUTHOR]

This piece is about reading, and what reading can do. It is written from a tangled complex of arts, philosophies, and literatures as it moves across land, with sea, and into air, through the content and expressions of an art museum exhibition about migrations of human and non-human bodies. The complex is serialized, broken apart, and pierced with art, as well as ideas developed by Gilles Deleuze through his readings of Lewis Carroll, among others—also read and pilfered alongside the current writing. A fragment of what follows is grounded; it is about earth, and lays out dimensions of reading, concepts of difference, and creativeness. Moving across land, and passing through art galleries, a second portion is of seas, drifts on waves, and into a third section comprised of air, art, and related arrangements. [ABSTRACT FROM AUTHOR]

Contact shots to the head often leave behind biological traces inside firearm barrels, a phenomenon of great forensic interest. Until now, the visualization and preservation of these traces presented a significant challenge, lacking a reliable method. This study addresses this gap by searching for a suitable method to extract the traces within a casting. Using alginate or gelatine as suitable materials, the results were hampered by serious adhesion issues and their extraction out of the firearm barrel was impeded. Finally, the combination of 11% gelatine with 1% alginate, introduced into the barrel around a 'central spine', succeeded to consistently produce replicable castings. Experimental contact shots displayed a distinct staining gradient from the muzzle to the rear of the barrel, as revealed through endoscopy and proved in the macroscopic casting. The technique proved effective for various common handgun barrels and successfully preserved blood and gunshot residue (GSR) patterns within the barrel. This method offers the dual benefits of visually mapping staining patterns and securing localized samples for targeted molecular genetic analysis in forensic investigations. [ABSTRACT FROM AUTHOR]

The evolution of classification of renal tumors has been impacted since the turn of the millennium by rapid progress in histopathology, immunohistochemistry, and molecular genetics. Together, these features have enabled firm recognition of specific, classic types of renal cell carcinomas, such as clear cell renal cell carcinoma, that in current practice trigger histologic-type specific management and treatment protocols. Now, the fifth Edition World Health Classification's new category of "Molecularly defined renal carcinomas" changes the paradigm, defining a total of seven entities based specifically on their fundamental molecular underpinnings. These tumors, which include TFE3 -rearranged, TFEB -altered, ELOC -mutated, fumarate hydratase-deficient, succinate dehydrogenase-deficient, ALK -rearranged, and SMARCB1 -deficient renal medullary carcinoma, encompass a wide clinical and histopathologic phenotypic spectrum of tumors. Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review. [ABSTRACT FROM AUTHOR]

Exome sequencing (ES) is a useful tool in diagnosing suspected mitochondrial disease but can miss pathogenic variants for several reasons. Additional testing, such as muscle biopsy or biochemical testing, can be helpful in exome-negative cases. We report a patient who presented with repeated episodes of lactic acidosis and failure to thrive. ES and mitochondrial sequencing were initially negative but clinical suspicion for mitochondrial disease remained high. After muscle biopsy showed evidence of mitochondrial dysfunction, the ES was reanalyzed and revealed novel variants in AARS2. This case demonstrates the importance of muscle biopsy and biochemical testing in evaluating patients with a high suspicion of mitochondrial disease, even in the genomics era. Closed-loop communication between molecular genetics laboratories and clinical geneticists is an important step to help establish diagnosis in unsolved cases. [ABSTRACT FROM AUTHOR]

Pseudohypoparathyroidism (PHP) represents a group of disorders due to end organ resistance to the actions of parathyroid hormone (PTH) and abnormalities in the PTH signalling pathway. PHP is characterized by hypocalcaemia and hyperphosphataemia, with or without a variable expression of physical features. The constellations of these physical features together are termed Albright hereditary osteodystrophy (AHO). PHP and related disorders are primarily clinical diagnoses in our setting as confirmatory laboratory testing is not widely available. Molecular genetics is the gold standard for confirmation and categorization of PHP into the different subtypes, but with recent advances in molecular diagnostics a pathophysiological approach appears to be more practical in the clinical setting. We present here the clinical course of a family of Pseudohypoparathyroidism who have been followed up at Paediatric Department of our hospital. The cases responded well with calcium and calcitriol supplementation without access to genetic testing in our hospital. [ABSTRACT FROM AUTHOR]

Promoters are essential elements of DNA sequence, usually located in the immediate region of the gene transcription start sites, and play a critical role in the regulation of gene transcription. Its importance in molecular biology and genetics has attracted the research interest of researchers, and it has become a consensus to seek a computational method to efficiently identify promoters. Still, existing methods suffer from imbalanced recognition capabilities for positive and negative samples, and their recognition effect can still be further improved. We conducted research on E. coli promoters and proposed a more advanced prediction model, iProL, based on the Longformer pre-trained model in the field of natural language processing. iProL does not rely on prior biological knowledge but simply uses promoter DNA sequences as plain text to identify promoters. It also combines one-dimensional convolutional neural networks and bidirectional long short-term memory to extract both local and global features. Experimental results show that iProL has a more balanced and superior performance than currently published methods. Additionally, we constructed a novel independent test set following the previous specification and compared iProL with three existing methods on this independent test set. [ABSTRACT FROM AUTHOR]

Human activities and climate change have resulted in frequent and intense weather fluctuations, leading to diverse abiotic stresses on crops which hampers greatly their metabolic activities. Heat stress, a prevalent abiotic factor, significantly influences cotton plant biological activities resulting in reducing yield and production. We must deepen our understanding of how plants respond to heat stress across various dimensions, encompassing genes, RNAs, proteins, metabolites for effective cotton breeding. Multi-omics methods, primarily genomics, transcriptomics, proteomics, metabolomics, and phenomics, proves instrumental in studying cotton’s responses to abiotic stresses. Integrating genomics, transcriptomics, proteomics, and metabolomic is imperative for our better understanding regarding genetics and molecular basis of heat tolerance in cotton. The current review explores fundamental omics techniques, covering genomics, transcriptomics, proteomics, and metabolomics, to highlight the progress made in cotton omics research. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a pathogenic bacterium that has claimed millions of lives since the Middle Ages. According to the World Health Organization's report, tuberculosis ranks among the ten deadliest diseases worldwide. The presence of an extensive array of genes and diverse proteins within the cellular structure of this bacterium has provided us with a potent tool for diagnosis. While the culture method remains the gold standard for tuberculosis diagnosis, it is possible that molecular diagnostic methods, emphasis on the identification of mutation genes (e.g., rpoB and gyrA) and single nucleotide polymorphisms, could offer a safe and reliable alternative. Over the past few decades, as our understanding of molecular genetics has expanded, methods have been developed based on gene expansion and detection. These methods typically commence with DNA amplification through nucleic acid targeted techniques such as polymerase chain reaction. Various molecular compounds and diverse approaches have been employed in molecular assays. In this review, we endeavor to provide an overview of molecular assays for the diagnosis of tuberculosis with their properties (utilization, challenges, and functions). The ultimate goal is to explore the potential of replacing traditional bacterial methods with these advanced molecular diagnostic techniques. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma is a rare disease, and its familial occurrence is quite uncommon. The aim of this paper is to report a three-generation phenotypical expression of a case familial occurrence of pheochromocytoma. Case presentation: A 25-year-old female, with a history of adrenalectomy for pheochromocytoma, arrived at the shock room during her third pregnancy with an adrenergic crisis and hypoglycemia. To prevent perinatal complications, the patient was stabilized and the newborn was delivered through a Kerr-type cesarean section. A detailed history revealed that the paternal grandfather of the patient had an unilateral pheochromocytoma, whereas her paternal uncle had a bilateral pheochromocytoma. Additionally, a brother of the patient presented a unilateral pheochromocytoma. Amplicons for PCR assays were designed to span the protein-coding segments of the three Von Hippel–Lindau (VHL) exons, and the PCR products were sequenced using the Sanger method. In the trace of exon 3, we detected in the sample of the proband a heterozygous guanine to adenine transition (NM_000551.4 c. 552G > A) within the protein-coding segment of exon 3 of the VHL gene, which leads to a substitution of the arginine residue at position 161 by a glutamine residue in the encoded peptide (NP_000542.1p.R161Q). This mutation was absent in two unaffected daughters. Conclusion: A VHL mutation was suspected and confirmed in this family that was not transmitted to a fourth generation. This case illustrates the importance of molecular genetics methodologies to assist genetic counseling in cases of pheochromocytoma where familial aggregation is presumed. [ABSTRACT FROM AUTHOR]

The process of identification and management of neurological disorder conditions faces challenges, prompting the investigation of novel methods in order to improve diagnostic accuracy. In this study, we conducted a systematic literature review to identify the significance of genetics- and molecular-pathway-based machine learning (ML) models in treating neurological disorder conditions. According to the study's objectives, search strategies were developed to extract the research studies using digital libraries. We followed rigorous study selection criteria. A total of 24 studies met the inclusion criteria and were included in the review. We classified the studies based on neurological disorders. The included studies highlighted multiple methodologies and exceptional results in treating neurological disorders. The study findings underscore the potential of the existing models, presenting personalized interventions based on the individual's conditions. The findings offer better-performing approaches that handle genetics and molecular data to generate effective outcomes. Moreover, we discuss the future research directions and challenges, emphasizing the demand for generalizing existing models in real-world clinical settings. This study contributes to advancing knowledge in the field of diagnosis and management of neurological disorders. [ABSTRACT FROM AUTHOR]

The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant to blood pressure regulation. Coldblooded trotters with the sub-elite haplotype had significantly higher blood pressure compared to horses with the elite performing haplotype during exercise. Alleles within the elite haplotype were part of the standing variation in pre-domestication horses, and have risen in frequency during the era of breed development and selection. These results advance our understanding of the molecular genetics of athletic performance and vascular traits in both horses and humans. Author summary: A previous study discovered that a genomic region close to the Endothelin3 gene was associated with harness racing performance. Here, careful phenotypic documentation of athletic performance and blood pressure measurements in horses, followed by state-of-the-art genomics, allowed us to identify a 5.5 kb regulatory region located approximately 50 kb 3' of the EDN3 gene. A comparative analysis of the region using human HiCap data supported a regulatory role as, in endothelial cells, interaction was observed between the region and multiple genes relevant to blood pressure regulation and athletic performance. Long range cis-regulatory modules are critical for cooperatively controlling multiple genes located within transcriptionally active domains. We measured blood pressure in Coldblooded trotters during exercise and demonstrated that horses with two copies of the elite-performing haplotype had lower blood pressure during exercise and better racing performance results, compared to horses with two copies of the sub-elite performing haplotype. In addition, horses with the elite-performing haplotype also had higher levels of Endothelin3 in plasma. The results reported here are important for understanding the biological mechanisms behind blood pressure regulation in relation to racing performance in both horses and humans. [ABSTRACT FROM AUTHOR]

SUMMARY: As a plant‐specific transcription factor, lateral organ boundaries domain (LBD) protein was reported to regulate plant growth and stress response, but the functional research of subfamily II genes is limited. SlMYC2, a master regulator of Jasmonic acid response, has been found to exhibit high expression levels in fruit and has been implicated in the regulation of fruit ripening and resistance to Botrytis. However, its role in fruit expansion remains unknown. In this study, we present evidence that a subfamily II member of LBD, namely SlLBD40, collaborates with SlMYC2 in the regulation of fruit expansion. Overexpression of SlLBD40 significantly promoted fruit growth by promoting mesocarp cell expansion, while knockout of SlLBD40 showed the opposite result. Similarly, SlMYC2 knockout resulted in a significant decrease in cell expansion within the fruit. Genetic analysis indicated that SlLBD40‐mediated cell expansion depends on the expression of SlMYC2. SlLBD40 bound to the promoter of SlEXPA5, an expansin gene, but did not activate its expression directly. While, the co‐expression of SlMYC2 and SlLBD40 significantly stimulated the activation of SlEXPA5, leading to an increase in fruit size. SlLBD40 interacted with SlMYC2 and enhanced the stability and abundance of SlMYC2. Furthermore, SlMYC2 directly targeted and activated the expression of SlLBD40, which is essential for SlLBD40‐mediated fruit expansion. In summary, our research elucidates the role of the interaction between SlLBD40 and SlMYC2 in promoting cell expansion in tomato fruits, thus providing novel insights into the molecular genetics underlying fruit growth. [ABSTRACT FROM AUTHOR]

Background: Fleas are one of the most common and pervasive ectoparasites worldwide, comprising at least 2500 valid species. They are vectors of several disease-causing agents, such as Yersinia pestis. Despite their significance, however, the molecular genetics, biology, and phylogenetics of fleas remain poorly understood. Methods: We sequenced, assembled, and annotated the complete mitochondrial (mt) genome of the rodent flea Nosopsyllus laeviceps using next-generation sequencing technology. Then we combined the new mitogenome generated here with mt genomic data available for 23 other flea species to perform comparative mitogenomics, nucleotide diversity, and evolutionary rate analysis. Subsequently, the phylogenetic relationship within the order Siphonaptera was explored using the Bayesian inference (BI) and maximum likelihood (ML) methods based on concentrated data for 13 mt protein-coding genes. Results: The complete mt genome of the rodent flea N. laeviceps was 16,533 base pairs (bp) in a circular DNA molecule, containing 37 typical genes (13 protein-coding genes, 22 transfer RNA [tRNA] genes, and two ribosomal RNA [rRNA] genes) with one large non-coding region (NCR). Comparative analysis among the order Siphonaptera showed a stable gene order with no gene arrangement, and high AT content (76.71–83.21%) with an apparent negative AT and GC skew except in three fleas Aviostivalius klossi bispiniformis, Leptopsylla segnis, and Neopsylla specialis. Moreover, we found robust evidence that the cytochrome c oxidase subunit 1 (cox1) gene was the most conserved protein-coding gene (Pi = 0.15, non-synonymous/synonymous [Ka/Ks] ratio = 0.13) of fleas. Phylogenomic analysis conducted using two methods revealed different topologies, but both results strongly indicated that (i) the families Ceratophyllidae and Leptopsyllidae were paraphyletic and were the closest to each other, and (ii) the family Ctenophthalmidae was paraphyletic. Conclusions: In this study, we obtained a high-quality mt genome of the rodent flea N. laeviceps and performed comparative mitogenomics and phylogeny of the order Siphonaptera using the mt database. The results will enrich the mt genome data for fleas, lay a foundation for the phylogenetic analysis of fleas, and promote the evolutionary analysis of Siphonaptera. [ABSTRACT FROM AUTHOR]

Currently, the control of rhizosphere selection on farms has been applied to achieve enhancements in phenotype, extending from improvements in single root characteristics to the dynamic nature of entire crop systems. Several specific signals, regulatory elements, and mechanisms that regulate the initiation, morphogenesis, and growth of new lateral or adventitious root species have been identified, but much more work remains. Today, phenotyping technology drives the development of root traits. Available models for simulation can support all phenotyping decisions (root trait improvement). The detection and use of markers for quantitative trait loci (QTLs) are effective for enhancing selection efficiency and increasing reproductive genetic gains. Furthermore, QTLs may help wheat breeders select the appropriate roots for efficient nutrient acquisition. Single-nucleotide polymorphisms (SNPs) or alignment of sequences can only be helpful when they are associated with phenotypic variation for root development and elongation. Here, we focus on major root development processes and detail important new insights recently generated regarding the wheat genome. The first part of this review paper discusses the root morphology, apical meristem, transcriptional control, auxin distribution, phenotyping of the root system, and simulation models. In the second part, the molecular genetics of the wheat root system, SNPs, TFs, and QTLs related to root development as well as genome editing (GE) techniques for the improvement of root traits in wheat are discussed. Finally, we address the effect of omics strategies on root biomass production and summarize existing knowledge of the main molecular mechanisms involved in wheat root development and elongation. [ABSTRACT FROM AUTHOR]

Introduction. Hepatic fibrosis (HF) is a complication of a congenital or acquired pathological process caused by an excess of non-functional liver tissue. The study aim was to assess the etiopathogenetic and diagnostic aspects of HF in children to evaluate surgical treatment. Materials and methods. The observational study was conducted within the CNSPCPP "Natalia Gheorghiu" of the MPHI Institute of Mother and Child, during 2018-2023, and reflects the results of the examination of 26 children aged 0-18 years diagnosed with HF caused by some congenital and acquired diseases. Paraclinical examinations included: liver ultrasound (USG) / liver elastography, MRI and CT imaging of the liver, molecular genetic testing (whole genome sequencing, next generation sequencing (NGS)), and liver biopsy. Statistical processing: through the Med Star (Medical Student Addiction Research) program. Results. In the 26 children diagnosed with HF, the following congenital pathologies were found Wilson's disease - 3 (11.53%) cases, biliary atresia - 6 (23.08%), autoimmune hepatitis - 2 (7.69%), sclerosing cholangitis - 2 (7.69%), glycogenosis - 2 (7.69%), congenital liver fibrosis - 2 (7.69%), hereditary hemochromatosis - 2 (7.69%) cases, as well as acquired pathologies such as: hepatitis B - 4 (15. 38%), hepatitis C - 3 (11.53%). In all children suspected of HF, changes in the biochemical examination of blood were detected, by increasing the values of liver enzymes, direct and indirect bilirubin, GGTP, alkaline phosphatase, LCTG, cholesterol, as well as increased levels of amylase, beta-lipoproteins, phospholipids, 5-nucleotidase, lipoprotein. There was a decrease in serum levels of total protein, albumin, and disorders of the coagulation system. USG/hepatic elastography revealed hepatosplenomegaly, increased echogenicity of liver tissue, decreased transhepatic perfusion with portal hypertension (HTP), and collaterals in the splanchnic bed. MRI of the liver was performed in 8 (30.78%) children in the cholangiographic regime and by CT with venous and arterial phase angiography - in 10 (38.46%) children. Characteristic changes for HF were assessed. The severity of HF was eloquent by the method of liver biopsy performed pre-and post-surgery. Histological changes of HF with varying degrees of impairment were found in all patients examined. Molecular genetic methods confirmed genetic diseases in 11 children with HF. Conclusions. HF occurs in many genetic and acquired pathologies and is associated with complex pathological mechanisms, with severe consequences and poor prognosis for the child's health. Early recognition of the symptoms of HF categorizes the investigations to identify the etiology of liver damage and suggests the type of treatment recommended individually. [ABSTRACT FROM AUTHOR]

Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas can be unilateral (60%–70%) or bilateral (30%–40%); bilateral tumors are always heritable and present at an earlier age as compared to unilateral ones (18–24 months vs. 36 months in India). High prevalence rates, delayed presentation, and inaccessibility to healthcare lead to worse outcomes in developing countries. The past few decades have seen a paradigm change in the treatment of retinoblastomas, shifting from enucleation and external beam radiotherapy to less aggressive modalities for eye salvage. Multimodality treatment is now the standard of care and includes intraarterial or intravenous chemotherapy along with focal consolidation therapies such as transpupillary thermotherapy, cryotherapy, and laser photocoagulation. Intravitreal and intracameral chemotherapy can help in controlling intraocular seeds. Advanced extraocular or metastatic tumors still have a poor prognosis. Genetic testing, counseling, and screening of at‑risk family members must be incorporated as essential parts of management. A better understanding of the genetics and molecular basis of retinoblastoma has opened up the path for potential targeted therapy in the future. Novel recent advances such as liquid biopsy, prenatal diagnosis, prognostic biomarkers, tylectomy, and chemoplaque point to promising future directions. [ABSTRACT FROM AUTHOR]

Objective To analyze the differences in molecular genetic characteristics between adult thalamic gliomas and brainstem gliomas to provide a basis for accurate diagnosis and treatment of adult thalamic gliomas. Methods The tumor tissue samples of 19 adult thalamic gliomas and 9 brainstem gliomas were collected. 425 tumor-related genes were detected by next-generation sequencing (NGS) . The variation in molecular genetic characteristics between adult thalamic gliomas and brainstem gliomas, such as gene point mutation and copy number variation, were analyzed. Results There was no significant difference in the incidence of diffuse midline glioma in the thalamus and brainstem of adults (P＞0. 05), but glioblastoma was more likely to occur in the thalamus (P=0. 026) . In adult thalamic gliomas, the ratio of TP53 mutation, TERT promoter mutation, CDK4/6 amplification, PTEN mutation and EGFR amplification were higher than those in adult brainstem gliomas, while the ratio of H3K27M mutation, IDH1 mutation, MCL1 amplification, NF1 mutation, ATRX mutation and FAT1 mutation were lower than those in adult brainstem gliomas. Of note, TERT promoter mutation significantly differed between adult thalamic gliomas and adult brainstem gliomas (P=0. 026) . The proportion of activation in PI3K signal pathway in adult thalamic gliomas was significantly higher compared to adult brainstem gliomas (P=0. 016) . Univariate analysis revealed that TP53 mutation (P=0. 01), CDK4/6 amplification (P=0. 02), EGFR amplification (P=0. 04) and ARID1A (P=0. 048) mutations were significantly associated with low survival in adult thalamic gliomas. In contrast, FAT1 mutation (P=0. 024) and MCL1 amplification (P=0. 017) were significantly associated with low survival in adult brainstem gliomas. Conclusions Glioblastoma is more likely to occur in adult thalamus than in brainstem, and there are significant differences in molecular genetic characteristics between the two, suggesting that adult thalamic glioma is a tumor with a special genetic tumor spectrum different from adult brain stem glioma. [ABSTRACT FROM AUTHOR]

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 "gain-of-function" variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders. [ABSTRACT FROM AUTHOR]

An epilepsy diagnosis reduces a patient's quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop its manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize the current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss the major molecular pathways involved, with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasized the role of the genetic background for the acquisition of epilepsy, including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase the vulnerability of the hippocampus to develop epilepsy following an injury—an emerging perspective on the epileptogenic process in acquired forms of epilepsy. [ABSTRACT FROM AUTHOR]