Genetic Differences Research Articles

Genetic ancestry-associated differences in genomic profiling and treatment patterns in pancreatic ductal adenocarcinoma (PDAC).

4138 Background: Prior epidemiological studies have explored race both as a population-level risk factor and as a factor influencing outcomes in PDAC. However, the impact of genetic ancestry on PDAC remains unclear. We assessed the genomic landscape, clinical care patterns, and outcomes across ancestries in a large and diverse PDAC cohort to determine the potential impact of genomics on ancestral disparities. Methods: A total of 24,948 patients diagnosed with PDAC who received tissue-biopsy based comprehensive genomic profiling (CGP; Foundation Medicine, Inc. (FMI)) as part of routine clinical care from Aug 2014-Sep 2023 were examined for genomic differences based on genetic ancestry which was determined using a SNP-based approach. The US-based de-identified Flatiron Health (FH)-FMI clinico-genomic database (CGDB) was used to assess testing and treatment patterns based on ancestry in 3,863 patients of European (EUR) and 414 patients of African (AFR) ancestry diagnosed with PDAC. Results: The genetic ancestry distribution in the overall cohort was 80.9% EUR, 10.0% AFR, 4.9% Admixed American, 3.5% East Asian, and 0.7% South Asian. AFR patients showed a slightly younger median age at biopsy than EUR (64 vs 67, p < .001). KRAS, TP53, CDKN2A/ 2B and SMAD4 were the most commonly altered genes in the cohort, as expected. Compared to EUR, AFR patients were enriched in alterations in TP53 (85% vs 78%, p < .001) and KRAS (95% vs 93%, p < .001). While rare, alterations in GNAS, CHEK2, and BRAF were observed less frequently in AFR (1.7% vs 3.3%, 0.3% vs 1.7%, 0.9% vs 2.2%, respectively, all p < .001). In the CGDB cohort, AFR patients were likely to have lower socioeconomic status (SES) compared to EUR patients (33% of AFR in the lowest SES quintile compared to 9% of EUR; p < .001 across all quintiles). AFR patients were less likely to receive care at academic centers (AFR 14.8% vs EUR 22.2%, p < .001) and less likely to receive an investigational drug during their cancer treatment course (5.9% vs 14.1%, p = .001). Rates of surgery (AFR 30.2% vs EUR 34.6%, p = .08), immunotherapy (3.2% vs 3.3%, p > .99), and targeted therapy (4.1% vs 6.2%, p = .28) were not significantly different. While AFR patients comprised a significantly larger proportion of AFR+EUR CGP volume following the decision to implement Medicare coverage for NGS testing (10.6% after Mar 16, 2018 vs 6.6% prior, p < .001), this remained below the expected based on share of the overall US population. Conclusions: To our knowledge, this is the largest study of genetic ancestry in PDAC to date. There were largely similar patterns of gene alterations across AFR and EUR ancestry groups suggesting non-genomic factors may underlie clinical outcomes disparities which have been reported in other studies. Notably, there were ancestry-based differences associated with SES and both CGP testing and clinical trial enrollment patterns, which may impact patient outcomes.

Genomic Characterization of Preclinical Prostate Cancer Cell Line Models.

As we move into the era of precision medicine, the growing relevance of genetic alterations to prostate cancer (PCa) development and treatment demonstrates the importance of characterizing preclinical models at the genomic level. Our study investigated the genomic characterization of eight PCa cell lines to understand which models are clinically relevant. We designed a custom AmpliSeq DNA gene panel that encompassed key molecular pathways targeting AR signaling, apoptosis, DNA damage repair, and PI3K/AKT/PTEN, in addition to tumor suppressor genes. We examined the relationship between cell line genomic alterations and therapeutic response. In addition, using DepMap's Celligner tool, we identified which preclinical models are most representative of specific prostate cancer patient populations on cBioPortal. These data will help investigators understand the genetic differences in preclinical models of PCa and determine which ones are relevant for use in their translational research.

Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review.

Traditional medication and alternative therapies have long been used to treat breast cancer. One of the main problems with current treatments is that there is an increase in drug resistance in the cancer cells owing to genetic differences such as mutational changes, epigenetic changes and miRNA (microRNA) alterations such as miR-1246, miR-298, miR-27b and miR-33a, along with epigenetic modifications, such as Histone3 acetylation and CCCTC-Binding Factor (CTCF) hypermethylation for drug resistance in breast cancer cell lines. Certain forms of conventional drug resistance have been linked to genetic changes in genes such as ABCB1, AKT, S100A8/A9, TAGLN2 and NPM. This review aims to explore the current approaches to counter breast cancer, the action mechanism, along with novel therapeutic methods endowing potential drug resistance. The investigation of novel therapeutic approaches sheds light on the phenomenon of drug resistance including genetic variations that impact distinct forms of oestrogen receptor (ER) cancer, genetic changes, epigenetics-reported resistance and their identification in patients. Long-term effective therapy for breast cancer includes selective oestrogen receptor modulators, selective oestrogen receptor degraders and genetic variations, such as mutations in nuclear genes, epigenetic modifications and miRNA alterations in target proteins. Novel research addressing combinational therapies including maytansine, photodynamic therapy, guajadiol, talazoparib, COX2 inhibitors and miRNA 1246 inhibitors have been developed to improve patient survival rates.

Genomic analysis of recurrent early stage and de novo metastatic colorectal cancer among veterans.

e15593 Background: The Veterans Health Administration (VHA) diagnoses approximately 4,000 cases of colon cancer each year and conducts Next Generation Sequencing (NGS) on recurrent and metastatic cases. The molecular profile of cancers resected for cure that recur is poorly characterized and holds promise to clarify both the risk and mechanisms of recurrence. We sought to characterize these genetic differences. Methods: A national database from the VHA consisting of colon cancer patients was analyzed for those with recurrent disease who have received NGS testing from 2015-2021. Data was analyzed by stage and presence of DNA mismatch repair (MMR) (MLH1, MSH2, PMS2, MSH6) and DNA damage repair (DDR) abnormalities (BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D) in addition to receipt of chemotherapy and overall survival with univariate and multivariate cox proportional hazards analyses and multivariate logistic regression analyses. Chi squared analyses were also performed comparing presence of DNA abnormalities between early recurrent and stage IV cancers. Results: From309,318 cases with colon cancer codes, we identified 2,366 colon cancer patients who had NGS and had recurrent or de novo metastatic disease. 1,072 patients had initial staging annotated (I n = 89, II n = 194, III n = 320 , IV n = 453). The average age was 69.41 years; 70.5% white, 21.5% Black and 7.8% other. Among all patients, DNA MMR abnormalities (n = 117) were associated with better overall survival, after controlling for age and race (HR 0.6, 95% CI 0.42-0.85, p < 0.005). Among recurrent early stage (I-III) and stage IV patients, MMR (n = 55 and n = 21, respectively) is associated with improved survival in multivariable models (HR 0.39, 95% CI 0.33-0.46, p < 0.001) . Among the 4 DNA MMR genes, MSH2 mutations had the strongest association with survival (univariate HR 0.31, 0.15-0.62, p < 0.001). Among patients with MMR abnormalities, those who received either only capecitabine or only fluorouracil (without irinotecan or oxaliplatin) had worse overall survival (HR 2.6, 1.34 -5.04, p < 0.005). This effect was more pronounced in early stage recurrent patients versus patients with de novo metastatic disease (HR 5.1, 1.87 – 13.9, p < 0.001). Finally, we also found that early stage patients with recurrent disease are more likely to have MMR abnormalities compared to de novo metastatic (8.8% vs 4.6%, p < 0.01) and confirmed this finding after controlling for race and age. (OR 2.13, p < 0.005). Conclusions: Among Veteranswith colon cancer, resected recurrent colon cancer is more likely to have DNA MMR abnormalities than de novo metastatic disease. Veterans with recurrent and or metastatic disease with DNA MMR have better outcomes regardless of stage at diagnosis. These findings suggest different pathogenesis for those with recurrent disease after curative resection, and for those with de novo metastatic disease.

Genomic analysis of the tumor microenvironment in Asian and Native Hawaiian and Pacific Islander patients with triple negative breast cancer.

e12644 Background: Triple negative breast cancer (TNBC) accounts for approximately 10- 20% of breast cancer cases and has the worst overall survival and prognosis compared to other subtypes. Unlike other subtypes, patients with TNBC are responsive to neoadjuvant therapy. A higher percent of stromal tumor infiltrating lymophocytes (sTILs) in the tumor microenvironment of TNBC correlates with an improved prognosis. Previous studies demonstrate that Native Hawaiians and Pacific Islanders (NHPIs) and Asians have equivocal percent of sTILs. Yet NHPIs have a higher mortality rate at 24.9% compared to Asians at 11%. Our study aims to molecularly characterize the tumor microenvironment in a diverse population of patients with TNBC who received neoadjuvant therapy. Methods: Retrospective chart review was conducted on 12 Asians and 12 NHPI patients with early stage TNBC from 2015 to 2022 from a medical oncology clinic within the Hawai’i Pacific Health system. Patient data collected include age at diagnosis of breast cancer, histology, BMI, clinical stage, sTILs, residual cancer burden, neoadjuvant treatment, and pathologic complete response. Core biopsy samples were processed and analyzed using the nCounter Breast Cancer 360 Panel. Further analysis was obtained using the nSolver Advanced Analysis Module. Results: Patient characteristics are listed in the table. Most patients had the basal-like immunosuppressed TNBC subtype. Among differentially expressed genes between races, 31 genes were statistically significant. NHPIs expressed more IL12RB2 and MYC, and Asians expressed more FGFR4 and MLPH. Among responders compared to non-responders, 5 genes were statistically significant. Responders expressed more STC1 and PTGER3, and non-responders expressed more CRAYAB, TMPRSS2, and CHAD. Among old and young patients, 132 genes were statistically significant. Older patients expressed more FUT3 and CKMT1, and younger patients expressed more MMP7 and MIA. Conclusions: In this pilot study, the molecular and genetic differences suggest that the tumor microenvironment may play a role in treatment outcomes between NHPIs and Asians. Further analysis will be conducted to determine the differences in immune cell infiltration. [Table: see text]

Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory.

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

Genetic variation and phylogenetic analysis of 23 STR in Chinese Han population from Hainan, Southern China.

The forensic characteristics and genetic relationships of Hainan Han population are still not fully understood. The aim of this study was to investigate the forensic features and genetic variations of 23 short tandem repeat (STR) included in the HuaxiaTM Platinum system in Hainan Han and analyze the population genetic relationships between Hainan Han and other adjacent Chinese populations. The genetic polymorphisms of 23 STR loci included in the HuaxiaTM Platinum kit were evaluated from 2971 Hainan Han individuals. Comprehensive comparisons were conducted based on genetic distance, phylogenetic tree, multidimensional scaling and principal component analysis (PCA) to explore inter-population genetic relationship. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) of the 23 STR loci was 0.999 999 999 999 999 999 999 999 999 819 and 0.999 999 999 625 408, respectively. The investigated Hainan Han population has high genetic similarity with geographically close Han populations, while great genetic difference with other ethnic minorities, prominently in Yunnan Miao, Xinjiang Uygurs, Xinjiang Kazakh, and Tibetans. Our study found the 23 STR loci were highly polymorphic and suitable for forensic personal identification and paternity testing in Hainan Han population. Genetic similarity widely existed among Han populations from different regions, and significant genetic divergence existed between Han populations and some ethnic minorities. The populations genetic diversity and similarity were closely associated with ethnic origin and geographical distribution.

Genomic approachesidentifySTT4 as a new component in glucose-induced activation of yeast plasma membrane H+-ATPase

Many studies have focused on identifying the signaling pathway by which addition of glucose triggers post-translational activation of the plasma membrane H+-ATPase in yeast. They have revealed that calcium signaling is involved in the regulatory pathway, supported for instance by the phenotype of mutants inARG82 that encodes an inositol kinase that phosphorylates inositol triphosphate (IP3). Strong glucose-induced calcium signaling, and high glucose-induced plasma membrane H+-ATPase activation have been observed in a specific yeast strain with the PJ genetic background. In this study, we have applied pooled-segregant whole genome sequencing, QTL analysis and a new bioinformatics methodology for determining SNP frequencies to identify the cause of this discrepancy and possibly new components of the signaling pathway. This has led to the identification of an STT4 allele with 6 missense mutations as a major causative allele, further supported by the observation that deletion of STT4 in the inferior parent caused a similar increase in glucose-induced plasma membrane H+-ATPase activation. However, the effect on calcium signaling was different indicating the presence of additional relevant genetic differences between the superior and reference strains. Our results suggest that phosphatidylinositol-4-phosphate might play a role in the glucose-induced activation of plasma membrane H+-ATPase by controlling intracellular calcium release through the modulation of the activity of phospholipase C.

Ongoing borealization of Siberian Arctic marine ichthyofauna: Further evidence

The occurrence, abundance, biomass and size composition of six boreal fish species (walleye pollock Gadus chalcogrammus, Pacific cod G. macrocephalus, northern wolffish Anarhichas denticulatus, beaked redfish Sebastes mentella, Greenland halibut Reinhardtius hippoglossoides, glacier lanternfish Benthosema glaciale) in the Siberian and Pacific Arctic are presented based on the analysis of open databases (OBIS, GBIF and FishBase) and the results of scientific surveys of TINRO 1977–2020. In open databases, information on the records of these species is available mainly for the eastern Chukchi Sea and the Beaufort Sea and is practically absent for the seas of the Siberian Arctic, which is due to technical reasons. Data from long–term surveys of TINRO indicate the extension of the ranges of North Atlantic species eastward and North Pacific species westward indicating the ongoing borealization of the Siberian Arctic due to a changing climate. At the species level, it can lead to the overlap of the ranges of the “western” and “eastern” populations of Greenland halibut, as well as the ranges of Pacific and Greenland cods, which will make it possible to exchange genetic material between these populations/species and will contribute to the disappearance of genetic differences between them.

Patterns of the Predicted Mutation Burden in 19,778 Domesticated Barley Accessions Conserved Ex Situ.

Long-term conservation of more than 7 million plant germplasm accessions in 1750 genebanks worldwide is a challenging mission. The extent of deleterious mutations present in conserved germplasm and the genetic risk associated with accumulative mutations are largely unknown. This study took advantage of published barley genomic data to predict sample-wise mutation burdens for 19,778 domesticated barley (Hordeum vulgare L.) accessions conserved ex situ. It was found that the conserved germplasm harbored 407 deleterious mutations and 337 (or 82%) identified deleterious alleles were present in 20 (or 0.1%) or fewer barley accessions. Analysis of the predicted mutation burdens revealed significant differences in mutation burden for several groups of barley germplasm (landrace > cultivar (or higher burden estimate in landrace than in cultivar); winter barley > spring barley; six-rowed barley > two-rowed barley; and 1000-accession core collection > non-core germplasm). Significant differences in burden estimate were also found among seven major geographical regions. The sample-wise predicted mutation burdens were positively correlated with the estimates of sample average pairwise genetic difference. These findings are significant for barley germplasm management and utilization and for a better understanding of the genetic risk in conserved plant germplasm.

Physical and chemical characterization of guava (Psidium guajava L.) genotypes grown in subtropical condition

Guava is a high-value tropical fruit that is widely grown in tropical and subtropical regions around the world. In the adaptation studies carried out in Turkey, guava was determined as the most prominent species with its cold resistance feature. The use of seedlings in cultivation created a genetic variation and differences were observed between the resulting genotypes, especially in terms of fruit size, shape and colour. Based on this observation, this study aimed to characterize 13 different guava fruit genotypes based on physical, chemical, bioactive and aroma properties. In the adaptation studies carried out in Turkey, guava was determined as the most prominent species with its cold resistance feature. There is only one commercial variety namely ‘Ruby Supreme’ grown in Turkey. Presently, the interest of the guava cultivation has been increased and farmers were used seedling material instead of vegetative to establish orchard. Due to the cross pollination, it has been observed great variation in the population. Therefore, it is important to select promising genotypes according to fruit size, shape and colour. The present study was evaluated 13 different guava genotypes according to physical, chemical, bioactive and aroma properties. Significant differences were observed among the genotypes. One genotype was found superior over all the genotypes, in terms of fruit weight (131.44 g) and length (82.00 mm). Although three genotypes were having lower values than the other samples in results of total soluble solids, they had higher results in terms of antioxidant capacity and total phenolic content. Two genotypes formed a separate group from all other genotypes in terms of (Z)-3-Hexen-1-yl acetate (sweet, pear, melon), 3-Hexenal (melon, tropical) and Ethyl alcohol (fruit and sweet) components. The flavor components are distinctive for the guava samples, as are the physical properties. It was also determined that the white guava genotypes had very different chemical and aromatic properties from other genotypes. The promising genotypes can be utilized in the future breeding programme to improve new guava varieties.

Genetic Characterization of Endangered Sterlet (Acipenser ruthenus, Linnaeus 1758) Gene Bank Broodstock, Natural and Cultured Populations in Hungary

The sterlet (Acipenser ruthenus) is the smallest-bodied endangered species among the six native sturgeon species of the Danube River, and self-sustaining populations still inhabit the Hungarian section of the Danube River and its largest tributary, the Tisza River. Their populations are drastically decreasing; however, they still have natural reproduction in these habitats. For the genetic conservation of the species, an ex situ gene bank is maintained in Hungary. The present study aimed to analyze the genetic resources of a gene bank with a near 40-year history and to compare it with natural populations and farmed stocks. Twelve microsatellites were used for population genetics analyses and individual genotyping of 268 specimens from two natural habitats (Danube and Tisza Rivers) and three captive stocks (a gene bank broodstock and two farms). Microsatellites revealed similar patterns among wild populations and gene bank stocks and did not show genetic differentiation (FST: 0.016–0.017) among them. These results confirmed that the gene bank broodstock properly represents the genetic background of the Danube and Tisza populations and is suitable as a source of breeding materials for the restocking programs. Negative trends were detected in the farmed stocks, reflected in reduced polymorphism at a few loci. The results of the principal component analyses indicate the farm stocks’ separation from the wild and gene bank stocks. The present genetic characterization study reveals a valuable captive stock of the endangered sterlet populations and provides unique information about the genetic similarities and differences among farms and wild stocks in Hungary. Our results provide information that contributes to preserving the genetic structure and variability in sterlet populations and supports the management of gene bank broodstock—avoiding inbreeding and preserving the unique genetic background of the Carpathian basin.

Genome-wide characterization and functional analysis of heat shock transcription factors in wild and cultivated rice (Oryza sativa L.)

Due to domestication, the genetic diversity in cultivated rice is lower than that of wild rice species. Recent progress in sequencing the genomes of wild and cultivated rice genus is an important step in identifying their genetic differences associated with abiotic and biotic stresses-resistant ability. Thus, in this study, heat shock transcription factor (Hsf) genes in 6 wild rice accessions, including Oryza barthii, Oryza glumaepatula, Oryza meridionalis, Oryza nivara, Oryza punctate and Oryza rufipogon, and 1 cultivated rice variety Nipponbare were firstly identified, and the evolution of rice Hsf genes were analyzed. Totally, 22, 23, 24, 24, 25, 25 and 25 Hsf genes were identified in the 7 tested rice genomes, Oryza barthii, Oryza glumaepatula, Oryza meridionalis, Oryza nivara, Oryza punctate, Oryza rufipogon and Oryza sativa, respectively. The evolutionary analysis of Hsf genes revealed that Oryza rufipogon was the immediate ancestral progenitor of Oryza sativa. The variation in the number of Hsf genes between wild and cultivated rice genotypes was mainly due to segmental duplication and whole genome duplication (WGD) events, which might contribute to the different stress-tolerant ability between the wild and cultivated rice varieties. Secondly, the function of the Hsf genes in wild and cultivated rice in response to salinity stress was compared. Under salt stress, four Hsf genes, HsfA2b, HsfB4b, HsfB4c and HsfB4d, were exclusively down-regulated in Oryza rufipogon shoots. Whilst, another four Hsf genes, HsfA7a, HsfB2c, HsfC1b and HsfC2b, were up-regulated in the shoots of both the cultivated rice and its ancestral progenitor Oryza rufipogon. Meanwhile, genomic comparison results showed that 1, 1, 5 and 5 nsSNPs were detected in these 4 Hsf genes respectively, which might alter the functions of these genes. RT-qPCR results further confirmed the expression profile of one of these 4 Hsf genes, HsfB2c. The expression pattern of this gene in the cultivated rice variety in response to salt stress was similar with the previously known salt stress-tolerant gene, WRKY28. This indicated that these 4 Hsf genes might be among the conserved genes related to salt stress tolerance in the wild and cultivated rice. In summary, these results provide novel clues to the further functional studies of Hsf genes in rice for breeding programs.

Genetic diversity and haplotypes of Cysticercus tenuicollis isolates from slaughtered sheep and goats in Elazig and Bingol provinces of Turkey.

The cestode Taenia hydatigena uses canids, primarily dogs, as definitive hosts, whereas the metacestode larval stage cysticercus infects a range of intermediate hosts, including domestic animals such as goats, sheep and pigs. In this study, we aimed to determine the genetic differences and haplotypes of Cysticercus tenuicollis isolates obtained from sheep and goats slaughtered in the Bingol and Elazig provinces of Turkey. C. tenuicollis isolates were collected from 44 sheep and 26 goats slaughtered in slaughterhouses in Bingol and Elazig. After the isolation of total genomic DNA from C. tenuicollis isolates, the genetic characterization of the partial mitochondrial cytochrome oxidase 1 (CO1) gene region (866bp) was amplified using specific primers by polymerase chain reaction (PCR), the products were then sequenced, and haplotype and genetic diversity analyses were carried out. As a result of the haplotype network analyses, 34 different haplotypes were detected around the main haplotype (Hap02) arranged in a star-like configuration and separated from other haplotypes by 1-28 mutation steps and covering 22.85% (16/70) of all isolates. Twenty-seven polymorphic fields were detected, 77.77% (21/27) of which were parsimony-informative, and secondary haplotype and nucleotide diversity were observed. Additionally, we detected high intraspecies haplotype diversity (hd: 0.933) and high nucleotide diversity (π: 0.00383), with 27 different nucleotide variation positions among the haplotypes of the isolates. Tajima's D value was negative, indicating population expansion and/or selection purification. The significantly negative Fu's Fs values indicated recent population expansion or the presence of expected rare haplotypes. The results of this study confirmed that C. tenuicollis isolates clustered in one lineage and were closely related to the relevant reference sequences in different countries, confirming the circulation of C. tenuicollis in different geographical regions.

Whole-genome selection signature differences between Chaohu and Ji'an red ducks.

Assessing the genetic structure of local varieties and understanding their genetic data are crucial for effective management and preservation. However, the genetic differences among local breeds require further explanation. To enhance our understanding of their population structure and genetic diversity, we conducted a genome-wide comparative study of Chaohu and Ji'an Red ducks using genome sequence and restriction site-associated DNA sequencing technology. Our analysis revealed a distinct genetic distinction between the two breeds, leading to divided groups. The phylogenetic tree for Chaohu duck displayed two branches, potentially indicating minimal impact from artificial selection. Additionally, our ROH (runs of homozygosity) analysis revealed that Chaohu ducks had a lower average inbreeding coefficient than Ji'an Red ducks. We identified several genomic regions with high genetic similarity in these indigenous duck breeds. By conducting a selective sweep analysis, we identified 574 candidate genes associated with muscle growth (BMP2, ITGA8, MYLK, and PTCH1), fat deposits (ELOVL1 and HACD2), and pigmentation (ASIP and LOC101797494). These results offer valuable insights for the further enhancement and conservation of Chinese indigenous duck breeds.

Translatability of life-extending pharmacological treatments between different species.

Anti-aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti-aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti-aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species-specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti-aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan.

Haemonchus contortus, an obligatory haematophagus worm infection in small ruminants: Population genetics and genetic diversity

Haemonchus contortus, a stomach worm, is prevalent in ruminants worldwide. They particularly hamper profitable small ruminant production. Here, we estimate the genetic variation of H. contortus collected from slaughtered goats and sheep from various geographic zones of Bangladesh using multiple genes. To perform this, adult parasites were isolated from the abomasum of slaughtered animals (sheep and goats). Among them, 79 male H. contortus were identified by microscopy. Following the extraction of DNA, ITS-2 and cox1 genes were amplified and subsequently considered for sequencing. After alignment and editing, sequences were analyzed to find out sequence variation, diversity pattern of genes, and population genetics of isolates. Among the sequence data, the analyses identified 19 genotypes of ITS-2 and 77 haplotypes of cox1 genes. The diversity of nucleotides was 0.0103 for ITS-2 and 0.029 for cox1 gene. The dendogram constructed by the genotype and haplotype sequences of H. contortus revealed that two populations were circulating in Bangladesh without any demarcation of host and geographic regions. Analysis of population genetics demonstrated a high flow of genes (89.2 %) within the population of the worm in Bangladesh. The Fst value showed very little amount of genetic difference among the worm populations of Bangladesh but marked genetic variation between different continents. The findings are expected to help explain the risks of anthelmintic resistance and the transmission pattern of the parasite, and also provide a control strategy against H. contortus.

Molecular Mechanisms of Genotype-Dependent Lifespan Variation Mediated by Caloric Restriction: Insight from Wild Yeast Isolates.

Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among the closely related species or strains of a single species. Since mitochondrial-mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect.

Sex or gender differences in treatment outcomes of sepsis and septic shock.

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer's disease pathogenesis

We analyzed data from human genome-wide association studies (GWASs) to identify genetic variants and biological pathways linked to Alzheimer's disease (AD). Ten AD biomarkers (APOE, NECTIN2, APOC1, APOC1P1, TOMM40, RNU4-67P, KRAS, Y_RNA, THORLNC, LINC01956) were found across studies, including six central genetic variants (MAPT (rs242557-A), GRIN2B (rs74442473-G), APOE (rs438811-T), ANK3 (rs438811-T), BIN1 (rs744373-G), and BDNF (rs7481773-A)). ANK3 (rs438811-T) and GRIN2B (rs74442473-G) were essential hub biomarkers for amyloid plaques, while MAPT (rs242557-A) and BIN1 (rs744373-G) were crucial for neurofibrillary tangles (NFTs). Higher-risk AD biomarkers were associated with increased protein-lipid complex formation, while lower-risk AD biomarkers were correlated with improved synaptic function. Six essential miRNAs (hsa-miR-124–3p, 15a-5p, 16–5p, 204–5p, 520g-3p, 520h) and three transcription factors (ZMAT4, ZBED6, FOXG1) emerged as possible candidates to reveal the genetic differences that lead to amyloid plaques, NFTs, and ultimately AD. These findings serve as a basis for potential AD treatments and offer new avenues for therapeutic approaches to directly target the genetic variations and processes associated with the disease.