Deciphering the Genetic Basis of Kernel Composition in a Maize Association Panel.

The primary objective in contemporary maize breeding is to pursue high quality alongside high yield. Deciphering the genetic basis of natural variation in starch, protein, oil, and fiber contents is essential for manipulating kernel composition, thereby enhancing the kernel quality and meeting growing demands. Here, we identified 12 to 88 statistically significant loci associated with kernel composition traits through a genome-wide association study (GWAS) using a panel of 212 diverse inbred lines. A regional association study pinpointed numerous causal candidate genes at these loci. Coexpression and protein-protein interaction network analyses of candidate genes revealed several causal genes directly or indirectly involved in the metabolic processes related to kernel composition traits. Subsequent mutant experiment revealed that nonsense mutations in ZmTIFY12 affect starch, protein, and fiber content, whereas nonsense mutations in ZmTT12 affect starch, protein, and oil content. These findings provide valuable guidance for improving kernel quality in maize breeding efforts.

Dissecting the genetic basis of UV-B responsive metabolites in rice.

BACKGROUND: UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. RESULTS: We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8groupA contributes to UV-B resistance in rice. CONCLUSIONS: Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.

An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes ZNF469 and PRDM5, from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases.

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes' development of aneurysmal and dissection diseases.

Theory of Mind: A Brief Review of Candidate Genes.

Deficits in theory of mind (ToM), known as the ability to understand the other's mind, have been associated with several psychopathological outcomes. The present systematic review aims to summarize the results of genetic studies that investigated gene polymorphisms associated with mentalization performance tasks in children and adults. The systematic review was carried out following PRISMA guidelines, and the literature search was conducted in PubMed and EBSCOhost using the following keywords: 'theory of mind, mentalizing, mindreading' and 'gene, genetic basis'. Nineteen studies met the eligibility criteria for inclusion. Most of the literature focused on the role of DRD4, DAT1, OXTR, OXT, COMT, ZNF804A, AVP, AVPR, SCL6A4, EFHC2, MAO-A, and the family of GTF2I genes in influencing ToM. However, controversial results emerged in sustaining the link between specific genetic polymorphisms and mentalization abilities in children and adults. Available data show heterogeneous outcomes, with studies reporting an association between the same family genes in subjects of the same age and other studies reporting no correlation. This does not allow us to draw any solid conclusions but paves the way for exploring genes involved in ToM tasks.

Uncovering the growing burden of enteric fever: A molecular analysis of Salmonella Typhi antimicrobial resistance.

Enteric fever, a persistent public health challenge in developing regions, is exacerbated by suboptimal socioeconomic conditions, contaminated water and food sources, and insufficient sanitation. This study delves into the antimicrobial susceptibility of Salmonella Typhi, uncovering the genetic underpinnings of its resistance. Analyzing 897 suspected cases, we identified a significant prevalence of typhoid fever, predominantly in males (58.3 %) and younger demographics. Alarmingly, our data reveals an escalation in resistance to both primary and secondary antibiotics, with cases of multi-drug resistant (MDR) and extensively drug-resistant (XDR) S. Typhi reaching 14.7 % and 43.4 %, respectively, in 2021. The Multiple Antibiotic Resistance (MAR) index exceeded 0.2 in over half of the isolates, signaling widespread antibiotic misuse. The study discerned 47 unique antibiotic resistance patterns and pinpointed carbapenem and macrolide antibiotics as the remaining effective treatments against XDR strains, underlining the critical need to preserve these drugs for severe cases. Molecular examinations identified blaTEM, blaSHV, and blaCTX-M genes in ceftriaxone-resistant strains, while qnrS was specific to ciprofloxacin-resistant variants. Notably, all examined strains exhibited a singular mutation in the gyrA gene, maintaining wild-type gyrB and parC genes. The erm(B) gene emerged as the primary determinant of azithromycin resistance. Furthermore, a distressing increase in resistance genes was observed over three years, with erm(B), blaTEM and qnrS showing significant upward trends. These findings are a clarion call for robust antimicrobial stewardship programs to curtail inappropriate antibiotic use and forestall the burgeoning threat of antibiotic resistance in S. Typhi.

Climate-related naturally occurring epimutation and their roles in plant adaptation in A. thaliana.

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens.

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

Mapping seasonal migration in a songbird hybrid zone -- heritability, genetic correlations, and genomic patterns linked to speciation.

Seasonal migration is a widespread behavior relevant for adaptation and speciation, yet knowledge of its genetic basis is limited. We leveraged advances in tracking and sequencing technologies to bridge this gap in a well-characterized hybrid zone between songbirds that differ in migratory behavior. Migration requires the coordinated action of many traits, including orientation, timing, and wing morphology. We used genetic mapping to show these traits are highly heritable and genetically correlated, explaining how migration has evolved so rapidly in the past and suggesting future responses to climate change may be possible. Many of these traits mapped to the same genomic regions and small structural variants indicating the same, or tightly linked, genes underlie them. Analyses integrating transcriptomic data indicate cholinergic receptors could control multiple traits. Furthermore, analyses integrating genomic differentiation further suggested genes underlying migratory traits help maintain reproductive isolation in this hybrid zone.

Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

Genetic Basis and Evolutionary Forces of Sexually Dimorphic Color Variation in a Toad-Headed Agamid Lizard.

In the animal kingdom, sexually dimorphic color variation is a widespread phenomenon that significantly influences survival and reproductive success. However, the genetic underpinnings of this variation remain inadequately understood. Our investigation into sexually dimorphic color variation in the desert-dwelling Guinan population of the toad-headed agamid lizard (Phrynocephalus putjatai) utilized a multidisciplinary approach, encompassing phenotypic, ultrastructural, biochemical, genomic analyses, and behavioral experiments. Our findings unveil the association between distinct skin colorations and varying levels of carotenoid and pteridine pigments. The red coloration in males is determined by a genomic region on chromosome 14, housing four pigmentation genes: BCO2 and three 6-pyruvoyltetrahydropterin synthases. A Guinan population-specific nonsynonymous single nucleotide polymorphism in BCO2 is predicted to alter the electrostatic potential within the binding domain of the BCO2-ß-carotene complex, influencing their interaction. Additionally, the gene MAP7 on chromosome 2 emerges as a potential contributor to the blue coloration in subadults and adult females. Sex-specific expression patterns point to steroid hormone-associated genes (SULT2B1 and SRD5A2) as potential upstream regulators influencing sexually dimorphic coloration. Visual modeling and field experiments support the potential selective advantages of vibrant coloration in desert environments. This implies that natural selection, potentially coupled with assortative mating, might have played a role in fixing color alleles, contributing to prevalence in the local desert habitat. This study provides novel insights into the genetic basis of carotenoid and pteridine-based color variation, shedding light on the evolution of sexually dimorphic coloration in animals. Moreover, it advances our understanding of the driving forces behind such intricate coloration patterns.

Diverse genetic basis of Vip3Aa resistance in five independent field-derived strains of Helicoverpa zea in the US.

BACKGROUND: Practical resistance of Helicoverpa zea to Cry proteins has become widespread in the US, making Vip3Aa the only effective Bacillus thuringiensis (Bt) protein for controlling this pest. Understanding the genetic basis of Vip3Aa resistance in H. zea is essential in sustaining the long-term efficacy of Vip3Aa. The objectives of this study were to characterize the inheritance of Vip3Aa resistance in four distinct field-derived H. zea strains (M1-RR, AC4-RR, R2-RR and R15-RR), and to test for shared genetic basis among these strains and a previously characterized Texas resistant strain (LT#70-RR). RESULTS: Maternal effects and sex linkage were absent, and the effective dominance level (DML) was 0.0 across Vip3Aa39 concentrations ranging from 1.0 to 31.6 µg cm-2, in all H. zea resistant strains. Mendelian monogenic model tests indicated that Vip3Aa resistance in each of the four strains was controlled by a single gene. However, interstrain complementation tests indicated that three distinct genetic loci are involved in Vip3Aa resistance in the five resistant H. zea strains: one shared by M1-RR and LT#70-RR; another shared by R2-RR and R15-RR; and a distinct one for AC4-RR. CONCLUSION: Results of this study indicate that Vip3Aa resistance in all H. zea strains was controlled by a single, recessive and autosomal gene. However, there were three distinct genetic loci associated with Vip3Aa resistance in the five resistant H. zea strains. The information generated from this study is valuable for exploring mechanisms of Vip3Aa resistance, monitoring the evolution of Vip3Aa resistance, and devising effective strategies for managing Vip3Aa resistance in H. zea. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Genetics and Genomics of Infectious Diseases in Key Aquaculture Species.

Diseases pose a significant and pressing concern for the sustainable development of the aquaculture sector, particularly as their impact continues to grow due to climatic shifts such as rising water temperatures. While various approaches, ranging from biosecurity measures to vaccines, have been devised to combat infectious diseases, their efficacy is disease and species specific and contingent upon a multitude of factors. The fields of genetics and genomics offer effective tools to control and prevent disease outbreaks in aquatic animal species. In this study, we present the key findings from our recent research, focusing on the genetic resistance to three specific diseases: White Spot Syndrome Virus (WSSV) in white shrimp, Bacterial Necrotic Pancreatitis (BNP) in striped catfish, and skin fluke (a parasitic ailment) in yellowtail kingfish. Our investigations reveal that all three species possess substantial heritable genetic components for disease-resistant traits, indicating their potential responsiveness to artificial selection in genetic improvement programs tailored to combat these diseases. Also, we observed a high genetic association between disease traits and survival rates. Through selective breeding aimed at enhancing resistance to these pathogens, we achieved substantial genetic gains, averaging 10% per generation. These selection programs also contributed positively to the overall production performance and productivity of these species. Although the effects of selection on immunological traits or immune responses were not significant in white shrimp, they yielded favorable results in striped catfish. Furthermore, our genomic analyses, including shallow genome sequencing of pedigreed populations, enriched our understanding of the genomic architecture underlying disease resistance traits. These traits are primarily governed by a polygenic nature, with numerous genes or genetic variants, each with small effects. Leveraging a range of advanced statistical methods, from mixed models to machine and deep learning, we developed prediction models that demonstrated moderate-to-high levels of accuracy in forecasting these disease-related traits. In addition to genomics, our RNA-seq experiments identified several genes that undergo upregulation in response to infection or viral loads within the populations. Preliminary microbiome data, while offering limited predictive accuracy for disease traits in one of our studied species, underscore the potential for combining such data with genome sequence information to enhance predictive power for disease traits in our populations. Lastly, this paper briefly discusses the roles of precision agriculture systems and AI algorithms and outlines the path for future research to expedite the development of disease-resistant genetic lines tailored to our target species. In conclusion, our study underscores the critical role of genetics and genomics in fortifying the aquaculture sector against the threats posed by diseases, paving the way for more sustainable and resilient aquaculture development.

A clinical and biologic review of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway caused by postzygotic somatic mutations. The estimated incidence of newborns with CMN is 1%-2%. The main complications of CMN include proliferative nodules, melanomas, and neurocutaneous melanosis, and the latter two are the most troublesome issues to address. Treatments are primarily taken into account for aesthetic purposes and the reduction of melanoma risk. Due to the much lower incidence of malignant transformation observed in recent studies than in previous data, clinical management paradigms for CMN patients have gradually shifted towards conservative observation and close monitoring. Surgery and lasers are still the main treatments, and targeted therapy may be a promising strategy to help manage complications. With the increase in awareness of mental health, increasing focus has been placed on the quality of life (QoL) and psychological issues of both CMN patients and their parents. Recent studies have revealed that families coping with CMN might endure intense pressure, a major loss in QoL, and psychological problems after diagnosis and during treatment. Here, we sought to present an overview of genetic basis, complications, treatments, and psychological issues related to CMN and hope to provide better management for patients with CMN.

The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders.

Rare genetic disorders (RDs), characterized by their low prevalence and diagnostic complexities, present significant challenges to healthcare systems. This article explores the transformative impact of artificial intelligence (AI) and machine learning (ML) in addressing these challenges. It emphasizes the need for accurate and early diagnosis of RDs, often hindered by genetic and clinical heterogeneity. This article discusses how AI and ML are reshaping healthcare, providing examples of their effectiveness in disease diagnosis, prognosis, image analysis, and drug repurposing. It highlights AI's ability to efficiently analyze extensive datasets and expedite diagnosis, showcasing case studies like Face2Gene. Furthermore, the article explores how AI tailors treatment plans for RDs, leveraging ML and deep learning (DL) to create personalized therapeutic regimens. It emphasizes AI's role in drug discovery, including the identification of potential candidates for rare disease treatments. Challenges and limitations related to AI in healthcare, including ethical, legal, technical, and human aspects, are addressed. This article underscores the importance of data ethics, privacy, and algorithmic fairness, as well as the need for standardized evaluation techniques and transparency in AI research. It highlights second-generation AI systems that prioritize patient-centric care, efficient patient recruitment for clinical trials, and the significance of high-quality data. The integration of AI with telemedicine, the growth of health databases, and the potential for personalized therapeutic recommendations are identified as promising directions for the field. In summary, this article provides a comprehensive exploration of how AI and ML are revolutionizing the diagnosis and treatment of RDs, addressing challenges while considering ethical implications in this rapidly evolving healthcare landscape.

Mutations in HA and PA affect the transmissibility of H7N9 avian influenza virus in chickens.

Low pathogenic (LP) H7N9 avian influenza virus (AIV) emerged in 2013 and had spread widely over several months in China, experienced a noteworthy reduction in isolation rate in poultry and human since 2017. Here, we examined the transmission of H7N9 viruses to better understand viral spread and dissemination mechanisms. Three out of four viruses (2013-2016) could transmit in chickens through direct contact, and airborne transmission was confirmed in the JT157 (2016) virus. However, we did not detect the transmission of the two 2017 viruses, WF69 and AH395, through either direct or airborne exposure. Molecular analysis of genome sequence of two viruses identified eleven mutations located in viral proteins (except for matrix protein), such as PA (K362R and S364N) and HA (D167N, H7 numbering), etc. We explored the genetic determinants that contributed to the difference in transmissibility of the viruses in chickens by generating a series of reassortants in the JT157 background. We found that the replacement of HA gene in JT157 by that of WF69 abrogated the airborne transmission in recipient chickens, whereas the combination of HA and PA replacement led to the loss of airborne and direct contact transmission. Failure with contact transmission of the viruses has been associated with the emergence of the mutations D167N in HA and K362R and S364N in PA. Furthermore, the HA D167N mutation significantly reduced viral attachment to chicken lung and trachea tissues, while mutations K362R and S364N in PA reduced the nuclear transport efficiency and the PA protein expression levels in both cytoplasm and nucleus of CEF cells. The D167N substitution in HA reduced the H7N9 viral acid stability and avian-like receptor binding, while enhanced human-like receptor binding. Further analysis revealed these mutants grew poorly in vitro and in vivo. To conclude, H7N9 AIVs that contain mutations in the HA and PA protein reduced the viral transmissibility in chicken, and may pose a reduced threat for poultry but remain a heightened public health risk.

RBFOX1 and Working Memory: From Genome to Transcriptome Revealed Posttranscriptional Mechanism Separate From Attention-Deficit/Hyperactivity Disorder.

Background: Many psychiatric disorders share a working memory (WM) impairment phenotype, yet the genetic causes remain unclear. Here, we generated genetic profiles of WM deficits using attention-deficit/hyperactivity disorder samples and validated the results in zebrafish models. Methods: We used 2 relatively large attention-deficit/hyperactivity disorder cohorts, 799 and 776 cases, respectively. WM impairment was assessed using the Rey Complex Figure Test. First, association analyses were conducted at single-variant, gene-based, and gene-set levels. Deeper insights into the biological mechanism were gained from further functional exploration by bioinformatic analyses and zebrafish models. Results: Genomic analyses identified and replicated a locus with rs75885813 as the index single nucleotide polymorphism showing significant association with WM defects but not with attention-deficit/hyperactivity disorder. Functional feature exploration found that these single nucleotide polymorphisms may regulate the expression level of RBFOX1 through chromatin interaction. Further pathway enrichment analysis of potential associated single nucleotide polymorphisms revealed the involvement of posttranscription regulation that affects messenger RNA stability and/or alternative splicing. Zebrafish with functionally knocked down or genome-edited rbfox1 exhibited WM impairment but no hyperactivity. Transcriptome profiling of rbfox1-defective zebrafish indicated that alternative exon usages of snap25a might partially lead to reduced WM learning of larval zebrafish. Conclusions: The locus with rs75885813 in RBFOX1 was identified as associated with WM. Rbfox1 regulates synaptic and long-term potentiation-related gene snap25a to adjust WM at the posttranscriptional level.

Complete genome analysis of Lactiplantibacillus plantarum VHProbi P06, a novel probiotic that resists Streptococcus pneumoniae in the upper respiratory tract.

The purpose of this study was to screen lactic acid bacteria active against Streptococcus pneumoniae and to analyze the genetic basis of their probiotic functions from the genome. We isolated a novel Lactiplantibacillus plantarum VHProbi P06 from pickles, which showed strong antibacterial activity against S. pneumoniae, adhesion to 5-8F cells, and inhibition of S. pneumoniae colonization in the respiratory tract. Genome of VHProbi P06 was analyzed, we found one class II bacteriocin synthesis gene cluster. Genome of the strain contained 42 adhesion-related protein-coding genes, and implicated three exopolysaccharide biosynthesis gene clusters with low homologous to L. plantarum WCFS1. Moreover, VHProbi P06 possessed 3 intact phage regions and 117 Carbohydrate Active Enzyme genes. By comparing the genomes of five L. plantarum, 275 unique genes were found in VHProbi P06. Finally, the gene prediction was verified, the bacteriocin PlnJK produced by P06 was identified by LC-MS/MS, and the laminar exopolysaccharide with a weight-averaged molecular of 125.37 KDa was also found. This study provides a theoretical basis for the application of VHProbi P06 to the upper respiratory tract to resist pathogenic bacteria.

Decoding the invasive nature of a tropical pathogen of concern: The invasive non-Typhoidal Salmonella strains causing host-restricted extraintestinal infections worldwide.

Invasive-Non-Typhoidal Salmonella (iNTS) are the major cause of health concern in the low-income, under-developed nations in Africa and Asia that lack proper sanitation facilities. Around 5% of the NTS cases give rise to invasive, extraintestinal diseases leading to focal infections like osteomyelitis, meningitis, osteoarthritis, endocarditis and neonatal sepsis. iNTS serovars like S. Typhimurium, S. Enteritidis, S. Dublin, S. Choleraesuis show a greater propensity to become invasive than others which hints at the genetic basis of their emergence. The major risk factors attributing to the invasive diseases include immune-compromised individuals having co-infection with malaria or HIV, or suffering from malnutrition. The rampant use of antibiotics leading to the emergence of multi-drug resistant strains poses a great challenge in disease management. An extensive understanding of the iNTS pathogenesis and its epidemiology will open up avenues for the development of new vaccination and therapeutic strategies to restrict the spread of this neglected disease.

The Association of Novel Single-Nucleotide Variants in the Collagen Matrix-Encoding Gene PRDM5 with Aortic Aneurysmal Disease.

Thoracic aortic aneurysms are clinical conditions that are associated with severe clinical endpoints including dissection and rupture, potentially leading to sudden death. Contrary to their abdominal counterparts, thoracic aortic aneurysms are well-recognized to have a genetic basis underlying their development. Among all patients with aneurysmal disease who underwent clinical genetic screening in our program (N = 145), two patients were found to have variants of uncertain significance (VUS) in the PRDM5 gene. This gene is responsible for multiple regulatory functions in extracellular matrix development, and this is the first report, to our knowledge, to associate this gene with aortopathy.