Altered levels of IFN-γ, IL-4, and IL-5 depend on the TLR4 rs4986790 genotype in COPD smokers but not those exposed to biomass-burning smoke.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 (TLR4) single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the TLR4 gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels. Materials and methods: We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA. Results: The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG. Conclusion: The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.

Carbon-Coated MOF-Derived Porous SnPS3 Core-Shell Structure as Superior Anode for Sodium-Ion Batteries.

Metal thiophosphites have recently emerged as a hot electrode material system for sodium-ion batteries because of their large theoretical capacity. Nevertheless, the sluggish electrochemical reaction kinetics and drastic volume expansion induced by the low conductivity and inherent conversion-alloying reaction mechanism, require urgent resolution. Herein, a distinctive porous core-shell structure, denoted as SnPS3@C, is controllably synthesized by synchronously phosphor-sulfurizing resorcinol-formaldehyde-coated tin metal-organic framework cubes. Thanks to the 3D porous structure, the ion diffusion kinetics are accelerated. In addition, SnPS3@C features a tough protective carbon layer, which improves the electrochemical activity and reduces the polarization. As expected, the as-prepared SnPS3@C electrode exhibits superior electrochemical performance compared to pure SnPS3, including excellent rate capability (1342.4 and 731.1 mAh g-1 at 0.1 and 4 A g-1, respectively), and impressive long-term cycling stability (97.9% capacity retention after 1000 cycles at 1 A g-1). Moreover, the sodium storage mechanism is thoroughly studied by in-situ and ex-situ characterizations. This work offers an innovative approach to enhance the energy storage performance of metal thiophosphite materials through meticulous structural design, including the introduction of porous characteristics and core-shell structures.

Coeliac disease and postpartum depression: are they linked? A two-sample Mendelian randomization study.

Background: To explore the potential causal associations between coeliac disease(CD) and postpartum depression(PPD) by using two-sample Mendelian randomization(MR) analysis. Methods: The IEU OPEN GWAS project was utilized to identify genetic loci strongly associated with CD as instrumental variables (IVs), and MR analysis was performed using inverse variance weighting(IVW), weighted median, weighted model, and MR-Egger. MR analyses were used to examine whether there was a link between CD and PPD, with an OR and 95% CI. Meanwhile, the relationship between CD and depression(DP) was analyzed using MR. The sensitivity analysis was conducted using MR-Egger intercept analysis, Cochran's Q test, and leave-one-out analysis. Results: From the GWAS online database, 13 single-nucleotide polymorphisms (SNPs) were chosen as IVs. The IVW results showed a relationship between PPD and a genetically predicted risk of developing CD (OR = 1.022, 95% CI: 1.001-1.044, P = 0.043). However, the presence of DP was not linked with CD (OR=0.991, 95% CI: 0.978-1.003, P=0.151). Potential horizontal pleiotropy was not discovered using MR-Egger intercept analysis (PPD: P=0.725; DP: P=0.785), and Cochran's Q test for heterogeneity revealed no significant heterogeneity (PPD: P=0.486; DP: P=0.909). A leave-one-out analysis found that individual SNPs had minimal effect on overall causal estimations. Conclusion: MR research discovered a link between CD and PPD.

Genotyping-by-sequencing informs conservation of Andean palms sources of non-timber forest products.

Conservation and sustainable management of lineages providing non-timber forest products are imperative under the current global biodiversity loss. Most non-timber forest species, however, lack genomic studies that characterize their intraspecific variation and evolutionary history, which inform species' conservation practices. Contrary to many lineages in the Andean biodiversity hotspot that exhibit high diversification, the genus Parajubaea (Arecaceae) has only three species despite the genus' origin 22 million years ago. Two of the three palm species, P. torallyi and P. sunkha, are non-timber forest species endemic to the Andes of Bolivia and are listed as IUCN endangered. The third species, P. cocoides, is a vulnerable species with unknown wild populations. We investigated the evolutionary relationships of Parajubaea species and the genetic diversity and structure of wild Bolivian populations. Sequencing of five low-copy nuclear genes (3753 bp) challenged the hypothesis that P. cocoides is a cultigen that originated from the wild Bolivian species. We further obtained up to 15,134 de novo single-nucleotide polymorphism markers by genotyping-by-sequencing of 194 wild Parajubaea individuals. Our total DNA sequencing effort rejected the taxonomic separation of the two Bolivian species. As expected for narrow endemic species, we observed low genetic diversity, but no inbreeding signal. We found three genetic clusters shaped by geographic distance, which we use to propose three management units. Different percentages of missing genotypic data did not impact the genetic structure of populations. We use the management units to recommend in situ conservation by creating new protected areas, and ex situ conservation through seed collection.

Pharmacogenetics of Calcineurin inhibitors in kidney transplant recipients: the African gap. A narrative review.

Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.

Research on the pharmacogenetics of calcineurin inhibitors in kidney transplant recipients is truly wanting in data from the African continent. Given Africa's vast genetic diversity, it is necessary to intensify efforts to generate data from Africa in this field.

Exploring Causal Links Between Gut Microbiota and Geriatric Syndromes: A Two-Sample Mendelian Randomization Analysis.

Background: Both observational studies and clinical trials have demonstrated a link between the gut microbiota and the geriatric syndrome. Nevertheless, the exact nature of this relationship, particularly concerning causality, remains elusive. Mendelian randomization (MR) is a method of inference based on genetic variation to assess the causal relationship between an exposure and an outcome. In this study, we conducted a two-sample Mendelian randomization (TSMR) study to fully reveal the potential genetic causal effects of gut microbiota on geriatric syndromes. Methods: This study used data from genome wide association studies (GWAS) to investigate causal relationships between the gut microbiota and geriatric syndromes, including frailty, Parkinson's disease (PD), delirium, insomnia, and depression. The primary causal relationships were evaluated using the inverse-variance weighted method, MR Egger, simple mode, weighted mode and weighted median. To assess the robustness of the results, horizontal pleiotropy was examined through MR-Egger intercept and MR-presso methods. Heterogeneity was assessed using Cochran's Q test, and sensitivity was evaluated via the leave-one-out method. Results: We identified 41 probable causal relationships between gut microbiota and five geriatric syndrome-associated illnesses using the inverse-variance weighted method. Frailty showed five positive and two negative causal relationships, while PD revealed three positive and four negative causal connections. Delirium showed three positive and two negative causal relationships. Similarly, insomnia demonstrated nine positive and two negative causal connections, while depression presented nine positive and two negative causal relationships. Conclusions: Using the TSMR method and data from the public GWAS database and, we observed associations between specific microbiota groups and geriatric syndromes. These findings suggest a potential role of gut microbiota in the development of geriatric syndromes, providing valuable insights for further research into the causal relationship between gut microbiota and these syndromes.

The Effects of Two Selected Single Nucleotide Polymorphisms of the Fatty Acid Synthase Gene on the Fat Content and Fatty Acid Profile of Cow's Milk from the Polish Holstein-Friesian Red-and-White Breed versus Two Polish Red-and-White and Polish Red Conservation Breeds Kept in Poland.

Fatty acid synthase (FASN) is a metabolic enzyme responsible for the synthesis of fatty acids in milk and meat. The SNPs g.841G/C and g.17924A/G of the FASN gene significantly influence the fat and fatty acid content of milk from cows of various breeds. Therefore, these SNPs were selected for this study. This study aimed to analyze the relationship of SNPs and their genotypes with the fat content and fatty acid profile of milk from Polish Red-and-White (ZR), Polish Red (RP), and Polish Holstein-Friesian Red-and-White (RW) cows. Milk samples were obtained during a milking trial. SNP genotyping was performed using the real-time PCR (HRM) method. It was shown that SNPs (with specific genotypes) were significantly associated with the presence of fatty acids such as C18:1n9t and C18:2n6c in milk. In addition, it was found that the milk fat from the ZR (genotypic variant A/G, AA) and RP (genotypic variant GG, A/G) breeds often exhibited a more attractive fatty acids profile than the milk fat from RW cows. This information can be used by both cattle breeders and people interested in consuming functional foods.

Single nucleotide polymorphism profiles of canine T-cell and null-cell lymphomas.

Background: The histopathological classification of T-cell lymphoma (TCL) in humans has distinctive mutational genotyping that suggests different lymphomagenesis. A similar concept is assumed to be observed in dogs with different TCL phenotypes. Objective: This study aimed to identify the previously reported single-nucleotide polymorphisms (SNPs) in both human beings and dogs in canine TCLs and null-cell lymphomas (NCLs) and to design compatible oligonucleotides from each variant based on the multiplex polymerase chain reaction. Methods: Genomic DNA was extracted from 68 tumor specimens (62 TCLs and 6 NCLs) and 5 buffy coat samples from dogs with TCL. Four TCL subtypes and NCL were analyzed in 44 SNPs from 21 genes using the MassARRAY. Results: The greatest incidences of SNPs observed in all TCL subtypes and NCL ware SATB1 c.1259A > C, KIT c.1275A > G, SEL1L c.2040 + 200C > G, and TP53 c.1024C > T, respectively. Some SNP locations were statistically significant associated with NCL, including MYC p.S75F (p = 0.0003), TP53 p.I149N (p = 0.030), PDCD1 p.F37LX (p = 0.012), and POT1 p.R583* (p = 0.012). Conclusion: Each TCL histological subtype and NCL are likely to contain distinctive mutational genetic profiles, which might play a role in lymphoma gene-risk factors and might be useful for selecting therapeutic target drugs for each canine patient.

Exposure-associated DNA methylation among people exposed to multiple industrial pollutants.

BACKGROUND: Current research on the epigenetic repercussions of exposure to a combination of pollutants is limited. This study aims to discern DNA methylation probes associated with exposure to multiple pollutants, serving as early effect markers, and single-nucleotide polymorphisms (SNPs) as surrogate indicators for population susceptibility. The investigation involved the analysis of urine exposure biomarkers for 11 heavy metals (vanadium, arsenic, mercury, cadmium, chromium, nickel, lead, manganese, copper, strontium, thallium), polycyclic aromatic hydrocarbon (PAHs) (1-hydroxypyrene), genome-wide DNA methylation sequencing, and SNPs array on all study participants. The data were integrated with metabolomics information and analyzed both at a community level based on proximity to home addresses relative to the complex and at an individual level based on exposure biomarker concentrations. RESULTS: On a community level, 67 exposure-related CpG probes were identified, while 70 CpG probes were associated with urine arsenic concentration, 2 with mercury, and 46 with vanadium on an individual level. These probes were annotated to genes implicated in cancers and chronic kidney disease. Weighted quantile sum regression analysis revealed that vanadium, mercury, and 1-hydroxypyrene contributed the most to cg08238319 hypomethylation. cg08238319 is annotated to the aryl hydrocarbon receptor repressor (AHRR) gene, and AHRR hypomethylation was correlated with an elevated risk of lung cancer. AHRR was further linked to deregulations in phenylalanine metabolism, alanine, aspartate, and glutamate metabolism, along with heightened oxidative stress. Additionally, three SNPs (rs11085020, rs199442, and rs10947050) corresponding to exposure-related CpG probes exhibited significant interaction effects with multiple heavy metals and PAHs exposure, and have been implicated in cancer progression and respiratory diseases. CONCLUSION: Our findings underscore the pivotal role of AHRR methylation in gene-environment interactions and highlight SNPs that could potentially serve as indicators of population susceptibility in regions exposed to multiple heavy metals and PAHs.

Revealing of TLR-9 gene polymorphisms by qPCR HRM technique and their influence on TLR-9 serum level in acute myeloid leukemia patients: Case-control study.

Acute myeloid leukemia (AML) is one of the most common and fatal malignancies that affect adults, which can quickly become aggressive if left untreated, and leukemia cells invade the bone marrow. TLR-9 is an innate immune cell receptor sensitive to various PAMPs and encoded by the TLR-9 gene. As is often known, genetic polymorphisms in any gene can help the development of the disease, and these three polymorphisms, rs187084, rs5743836, and rs352140 of TLR-9, have been studied in many different cancer disorders. Therefore, this study aimed to discover the multiple forms of a TLR-9 gene in a sample of Iraqi AML patients. A total of 120 participants in a case-control study were enrolled in the current study. Using CBC, some hematological parameters were evaluated, and the serum level of TLR-9 was assessed using the ELISA technique. DNA was extracted directly from blood, and a high-resolution melting (HRM) analysis was then carried out. The results revealed a significant difference in some blood parameters among patients and healthy control, while WBC and lymphocytes were without an evident difference between the two groups of the current investigation. The serum concentration of TLR-9 showed an elevated level in patients (P value < 0.01). Nonetheless, this increase was not affected by the genotype patterns of polymorphisms. According to the P-value, there was a significant difference in wild genotypes of the three polymorphisms (rs187084, rs5743836, and rs352140). At the same time, the odds ratio revealed the association with the disease as a protective factor. In contrast, there was a significant difference in the heterozygous and mutant genotypes of TLR-9 polymorphisms, though the odds ratio confirmed the association with the AML as a risk factor. The results of rs352140 were compatible with H.W.E since there were no significant differences between the observed and expected values for either patients or healthy controls. In contrast, the result of rs5743836 was not consistent with the HWE. Furthermore, although it corresponds with the healthy one, the finding of rs187084 conflicted with H.W.E. in the patient group. In conclusion, High serum levels of TLR-9 in patients could act as biomarkers for AML. The TLR-9 gene polymorphisms (rs187084, rs5743836, and rs352140) have been linked to an increased risk of AML and may impact the disease progression in the Iraqi population.

Genotyping SNPs and Indels: A method to improve the scope and sensitivity of High-Resolution melt (HRM) analysis based applications.

High-resolution melt (HRM) analysis is a closed-tube technique for detecting single nucleotide polymorphisms (SNPs). However, it has limited use in high-resolution melting devices, even those with high thermal accuracy (HTA). In addition to the cost of switching to these specialized devices, the presence of nearest neighbour neutral changes (class III, IV SNPs and small indels) made HRM-based assays a challenging task due to reduced sensitivity. This study aimed to design a common modified competitive amplification of differently melting amplicons (CADMA)-based assay to address these challenges by generating allele-specific qPCR products that are detectable on most qPCR platforms. For this study, SNPs were selected from all four classes of SNPs (class I: C/T or G/A mutation; class II: C/A or G/T mutation; class III: G/C mutation; class IV: A/T mutation). A single base pair and 19 bp indels were also chosen to simulate how CADMA primers could be designed for indels of varying lengths. The melting temperatures (Tm) were determined using IDT oligoAnalyzer. qPCR and melt data acquisition were performed on the CFX96 qPCR platform, and the melt curve data were analyzed using Precision Melt software (Bio-Rad, USA). The clusters for different genotypes were successfully identified with the aid of the control samples, and Tm predictions were carried out using the uMelt batch and Tm online tools for comparison. Using HRM-qPCR assays based on the modified CADMA method, genotyping of various SNPs was successfully carried out. For some SNPs, similarly shaped melt curves were observed for homozygotes and heterozygotes, making shape-based genotype prediction difficult. The Tm values calculated via the Blake and Delcourts (1998) method were the closest to the experimental Tm values after adjusting for the salt concentration. Since HRM assays usually depend on the ΔTm caused by mutations, they are prone to a high error rate due to nearest neighbour neutral changes. The technique developed in this study significantly reduces the failure rates in HRM-based genotyping and could be applied to any SNP or indel in any platform. It is crucial to have a deep understanding of the melt instrument, its accuracy and the nature of the target (SNP class or indel length and GC content of the flanking region). Furthermore, the availability of controls is essential for a high success rate.

SATCAS: A CRISPR/Cas13a-based simultaneous amplification and testing platform for one-pot RNA detection and SNPs distinguish in clinical diagnosis.

The clinical diagnosis of pathogen infectious diseases increasingly requires sensitive and rapid RNA detection technologies. The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system has shown immense potential in molecular diagnostics due to its trans-cleavage activity. However, most Cas13a-based detection methods require an amplicon transcription step, and the multi-step open-tube operations are prone to contamination, limiting their widespread application. Here, we propose an ultrasensitive (single-copy range, ∼aM) and rapid (within 40 min) isothermal one-pot RNA detection platform, termed SATCAS (Simultaneous Amplification and Testing platform based on Cas13a). This method effectively distinguishes viable bacteria (0%-100%) under constant total bacterial conditions, demonstrating its robustness and universality. SATCAS excels in identifying single nucleotide polymorphisms (SNPs), particularly detecting 0.5% drug-resistant mutations. We validated SATCAS by detecting infections in biological samples from 68 HBV, 23 EBV, and 48 SARS-CoV-2 patients, achieving 100% sensitivity, 92.86% specificity, and 97.06% accuracy in HBV infection testing. We anticipate that SATCAS has broad application potential in the early diagnosis, subtyping, drug resistance detection, and point-of-care monitoring of pathogen infectious diseases.

A two sample mendelian randomization analysis investigates causal effects between gut microbiome and immune related Vasculitis.

Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

No causal relationship between serum vitamin D levels and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

Background: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD. Methods: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Results: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.

Inside Mycobacterium bovis SB0120 spoligotype circulating in Italy: analysis of the most frequent genotypes by whole genome sequencing.

Bovine tuberculosis (bTB) is a chronic inflammatory disease primarily caused by Mycobacterium bovis. The infection affects domestic animals and wildlife, posing a zoonotic risk to humans. To understand the dynamics of transmission and genetic diversity in Italy's M. bovis population, we conducted whole-genome sequencing (WGS) analysis on two prevalent genotypes, belonging to Spoligotype SB0120, identified in different geographical and temporal contexts. By comparing these genomes with international M. bovis isolates, we identified a distinct clade within the lineage La1.2, encompassing the Italian SB0120 isolates, indicating a genomic segregation of Italian M. bovis from other European isolates. Within Italy, a significant level of genetic variability emerged across regions, while isolates within epidemiologically linked outbreaks exhibited minimal genetic diversity. Additionally, isolates derived from cattle and wild boars within a tuberculosis hotspot in Central Italy and from cattle and black pigs in Sicily formed unified clonal clusters. This indicates the presence of persistent strains circulating in the examined regions. The genetic diversity within herds was limited, as specific clones endured over time within certain herds. This research enhances our comprehension of the epidemiology and transmission patterns of bTB in Italy, thereby aiding the development of precise control strategies and disease management. Using WGS and implementing standardized protocols and databases will be pivotal in combating bTB and promoting One-Health approaches to address this noteworthy public health concern.

Population structure and genetic diversity of mango (Mangifera indica L.) germplasm resources as revealed by single-nucleotide polymorphism markers.

Introduction: Mango is a vital horticultural fruit crop, and breeding is an essential strategy to enhance ongoing sustainability. Knowledge regarding population structure and genetic diversity in mango germplasm is essential for crop improvement. Methods: A set of 284 mango accessions from different regions of the world were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction to generate genomic single-nucleotide polymorphism (SNP). Results: After filtering, raw data containing 539.61 M reads were obtained. A total of 505,300 SLAFs were detected, of which, 205,299 were polymorphic. Finally, 29,136 SNPs were employed to dissect the population structure, genetic relationships, and genetic diversity. The 284 mango accessions were divided into two major groups: one group consisted mainly of mango accessions from Australia, the United States, Cuba, India, Caribbean, Israel, Pakistan, Guinea, Burma, China, and Sri Lanka, which belonged to the Indian type (P1); the other group contained mango accessions from the Philippines, Thailand, Indonesia, Vietnam, Cambodia, Malaysia, and Singapore, which belonged to Southeast Asian type (P2). Genetic diversity, principal component analysis (PCA), and population structure analyses revealed distinct accession clusters. Current results indicated that the proposed hybridization occurred widely between P1 and P2. Discussion: Most of the accessions (80.99%) were of mixed ancestry, perhaps including multiple hybridization events and regional selection, which merits further investigation.

Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing.

The common squid, Todarodes pacificus, is an important commercial species that inhabits the northwest Pacific Ocean, particularly the East Japan Sea, the Pacific coast of Japan, and the East China Sea. In this study, we chose 29 individuals from three areas: one type from the Sea of Japan and two types from the East China Sea. A total of 43,529 SNPs were obtained using genotyping-by-sequencing (GBS). Our analyses revealed low genetic diversity and genetic differentiation in each type. Heterozygote deficiency and inbreeding have caused this low level of genetic diversity. Population structure analysis indicated that the three types were genetically similar, which may be attributed to strong gene flow combined with the demographic history events during the last 2 million years. This new GBS application technique provides valuable information for the conservation of marine species genetics and could be useful for the effective management of this resource.

Identifying Oncogenic Missense Single Nucleotide Polymorphisms in Human SAT1 Gene Using Computational Algorithms and Molecular Dynamics Tools.

BACKGROUND: The human SAT1 gene encodes spermidine/spermine N1-acetyltransferase 1 (SSAT1), a regulatory biological catalyst of polyamine catabolism. Numerous essential biological processes, such as cellular proliferation, differentiation, and survival, depend on polyamines like spermidine and spermine. Thus, SSAT1 is involved in key cellular activities such as proliferation and survival of cells and mediates various diseases including cancer. A plethora of studies established the involvement of missense single nucleotide polymorphisms (SNPs) in numerous pathological conditions due to their ability to adversely affect the structure and subsequent function of the protein. AIMS: To date, an in silico study to identify the pathogenic missense SNPs of the human SAT1 gene has not been accomplished yet. This study aimed to filter the missense SNPs that were functionally detrimental and pathogenic. METHODS AND RESULTS: The rs757435207 (I21N) was ascertained to be the most deleterious and pathogenic by all algorithmic tools. Stability and evolutionary conservation analysis tools also stated that I21N variant decreased the stability and was located in the highly conserved residue. Molecular dynamics simulation revealed that I21N caused substantial alterations in the conformational stability and dynamics of the SSAT1 protein. Consequently, the I21N variant could disrupt the native functional roles of the SSAT1 enzyme. CONCLUSION: Therefore, the I21N variant was identified and concluded to be an oncogenic missense variant of the human SAT1 gene. Overall, the findings of this study would be a great directory of future experimental research to develop personalized medicine.

Genome-wide association analysis reveals the genetic basis of thermal tolerance in dwarf surf clam Mulinia lateralis.

Recently, elevated seawater temperatures have resulted numerous adverse effects, including significant mortality among bivalves. The dwarf surf clam, Mulinia lateralis, is considered a valuable model species for bivalve research due to its rapid growth and short generation time. The successful cultivation in laboratory setting throughout its entire life cycle makes it an ideal candidate for exploring the potential mechanisms underlying bivalve responses to thermal stress. In this study, a total of 600 clams were subjected to a 17-day thermal stress experiment at a temperature of 30 °C which is the semi-lethal temperature for this species. Ninety individuals who perished initially were classified as heat-sensitive populations (HSP), while 89 individuals who survived the experiment were classified as heat-tolerant populations (HTP). Subsequently, 179 individuals were then sequenced, and 21,292 single nucleotide polymorphisms (SNPs) were genotyped for downstream analysis. The heritability estimate for survival status was found to be 0.375 ± 0.127 suggesting a genetic basis for thermal tolerance trait. Furthermore, a genome-wide association study (GWAS) identified three SNPs and 10 candidate genes associated with thermal tolerance trait in M. lateralis. These candidate genes were involved in the ETHR/EHF signaling pathway and played pivotal role in signal sensory, cell adhesion, oxidative stress, DNA damage repair, etc. Additionally, qPCR results indicated that, excluding MGAT4A, ZAN, and RFC1 genes, all others exhibited significantly higher expression in the HTP (p < 0.05), underscoring the critical involvement of the ETHR/EHF signaling pathway in M. lateralis' thermal tolerance. These results unveil the presence of standing genetic variations associated with thermal tolerance in M. lateralis, highlighting the regulatory role of the ETHR/EHF signaling pathway in the bivalve's response to thermal stress, which contribute to comprehension of the genetic basis of thermal tolerance in bivalves.

Association between NEK1 gene polymorphisms and the potential risk of sporadic Parkinson's disease in the Chinese Northern Han population: A case-control study.

OBJECTIVE: Parkinson's disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer's disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population. METHODS: A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations. RESULTS: Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group. CONCLUSION: This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD.