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1.
Antimicrob Agents Chemother ; : e0161923, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712935

RESUMO

We used whole-genome sequencing to analyze a collection of 35 fluconazole-resistant and 7 susceptible Candida parapsilosis isolates together with coverage analysis and GWAS techniques to identify new mechanisms of fluconazole resistance. Phylogenetic analysis shows that although the collection is diverse, two persistent clinical lineages were identified. We identified copy number variation (CNV) of two genes, ERG11 and CDR1B, in resistant isolates. Two strains have a CNV at the ERG11 locus; the entire ORF is amplified in one, and only the promoter region is amplified in the other. We show that the annotated telomeric gene CDR1B is actually an artifactual in silico fusion of two highly similar neighboring CDR genes due to an assembly error in the C. parapsilosis CDC317 reference genome. We report highly variable copy numbers of the CDR1B region across the collection. Several strains have increased the expansion of the two genes into a tandem array of new chimeric genes. Other strains have experienced a deletion between the two genes creating a single gene with a reciprocal chimerism. We find translocations, duplications, and gene conversion across the CDR gene family in the C. parapsilosis species complex, showing that it is a highly dynamic family.

2.
Int J Bipolar Disord ; 12(1): 19, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758284

RESUMO

BACKGROUND: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. RESULTS: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. CONCLUSIONS: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.

3.
Crit Rev Oncol Hematol ; 199: 104379, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38718940

RESUMO

The emerging era of precision medicine is characterized by an increasing availability of targeted anticancer therapies and by the parallel development of techniques to obtain more refined molecular data, whose interpretation may not always be straightforward. Molecular tumor boards gather various professional figures, in order to leverage the analysis of molecular data and provide prognostic and predictive insights for clinicians. In addition to healthcare development, they could also become a tool to promote knowledge and research spreading. A growing body of evidence on the application of molecular tumor boards to clinical practice is forming and positive signals are emerging, although a certain degree of heterogeneity exists. This work analyzes molecular tumor boards' potential workflows, figures involved, data sources, sample matrices and eligible patients, as well as available evidence and learning examples. The emerging concept of multi-institutional, disease-specific molecular tumor boards is also considered by presenting two ongoing nationwide experiences.

4.
Sci Rep ; 14(1): 11339, 2024 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760387

RESUMO

Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).


Assuntos
Imageamento por Ressonância Magnética , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Radiômica
5.
Genome Biol Evol ; 16(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38761112

RESUMO

The increased availability of quality genomic data has greatly improved the scope and resolution of our understanding of the recent evolutionary history of wild species adapted to extreme environments and their susceptibility to anthropogenic impacts. The guanaco (Lama guanicoe), the largest wild ungulate in South America, is a good example. The guanaco is well adapted to a wide range of habitats, including the Sechura Desert, the high Andes Mountains to the north, and the extreme temperatures and conditions of Navarino Island to the south. Guanacos also have a long history of overexploitation by humans. To assess the evolutionary impact of these challenging habitats on the genomic diversity, we analyzed 38 genomes (∼10 to 16×) throughout their extensive latitudinal distribution from the Sechura and Atacama Desert to southward into Tierra del Fuego Island. These included analyses of patterns of unique differentiation in the north and geographic region further south with admixture among L. g. cacsilensis and L. g. guanicoe. Our findings provide new insights on the divergence of the subspecies ∼800,000 yr BP and document two divergent demographic trajectories and to the initial expansion of guanaco into the more southern portions of the Atacama Desert. Patagonian guanacos have experienced contemporary reductions in effective population sizes, likely the consequence of anthropogenic impacts. The lowest levels of genetic diversity corresponded to their northern and western limits of distribution and some varying degrees of genetic differentiation. Adaptive genomic diversity was strongly linked with environmental variables and was linked with colonization toward the south followed by adaptation.


Assuntos
Camelídeos Americanos , Animais , Camelídeos Americanos/genética , Ecossistema , Clima Desértico , Adaptação Fisiológica/genética , Genoma , Variação Genética , Regiões Antárticas , América do Sul , Evolução Molecular
6.
Front Microbiol ; 15: 1358574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774501

RESUMO

Mamiellophyceae are dominant marine algae in much of the ocean, the most prevalent genera belonging to the order Mamiellales: Micromonas, Ostreococcus and Bathycoccus, whose genetics and global distributions have been extensively studied. Conversely, the genus Mantoniella, despite its potential ecological importance, remains relatively under-characterised. In this study, we isolated and characterised a novel species of Mamiellophyceae, Mantoniella tinhauana, from subtropical coastal waters in the South China Sea. Morphologically, it resembles other Mantoniella species; however, a comparative analysis of the 18S and ITS2 marker genes revealed its genetic distinctiveness. Furthermore, we sequenced and assembled the first genome of Mantoniella tinhauana, uncovering significant differences from previously studied Mamiellophyceae species. Notably, the genome lacked any detectable outlier chromosomes and exhibited numerous unique orthogroups. We explored gene groups associated with meiosis, scale and flagella formation, shedding light on species divergence, yet further investigation is warranted. To elucidate the biogeography of Mantoniella tinhauana, we conducted a comprehensive analysis using global metagenomic read mapping to the newly sequenced genome. Our findings indicate this species exhibits a cosmopolitan distribution with a low-level prevalence worldwide. Understanding the intricate dynamics between Mamiellophyceae and the environment is crucial for comprehending their impact on the ocean ecosystem and accurately predicting their response to forthcoming environmental changes.

7.
Am J Psychiatry ; : appiajp20230247, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745458

RESUMO

OBJECTIVE: Treatment-resistant depression (TRD) occurs in roughly one-third of all individuals with major depressive disorder (MDD). Although research has suggested a significant common variant genetic component of liability to TRD, with heritability estimated at 8% when compared with non-treatment-resistant MDD, no replicated genetic loci have been identified, and the genetic architecture of TRD remains unclear. A key barrier to this work has been the paucity of adequately powered cohorts for investigation, largely because of the challenge in prospectively investigating this phenotype. The objective of this study was to perform a well-powered genetic study of TRD. METHODS: Using receipt of electroconvulsive therapy (ECT) as a surrogate for TRD, the authors applied standard machine learning methods to electronic health record data to derive predicted probabilities of receiving ECT. These probabilities were then applied as a quantitative trait in a genome-wide association study of 154,433 genotyped patients across four large biobanks. RESULTS: Heritability estimates ranged from 2% to 4.2%, and significant genetic overlap was observed with cognition, attention deficit hyperactivity disorder, schizophrenia, alcohol and smoking traits, and body mass index. Two genome-wide significant loci were identified, both previously implicated in metabolic traits, suggesting shared biology and potential pharmacological implications. CONCLUSIONS: This work provides support for the utility of estimation of disease probability for genomic investigation and provides insights into the genetic architecture and biology of TRD.

8.
Mol Ecol Resour ; : e13969, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747336

RESUMO

A major aim of evolutionary biology is to understand why patterns of genomic diversity vary within taxa and space. Large-scale genomic studies of widespread species are useful for studying how environment and demography shape patterns of genomic divergence. Here, we describe one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screened ca 500,000 SNP markers across 647 individuals from 29 populations, spanning ~30 degrees of latitude and 40 degrees of longitude - almost the entire geographical range of the European subspecies. Genome-wide variation was consistent with a recent colonisation across Europe from a South-East European refugium, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear 'islands of differentiation', even among populations with very low levels of genome-wide differentiation. Low local recombination rates were a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination causes highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, probably as a result of recent directional selection at the species' range edges. Haplotype-based measures of selection were related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into spatio-temporal evolutionary dynamics.

9.
Trends Parasitol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38755024

RESUMO

Anopheles stephensi is an invasive malaria vector in Africa that has been implicated in malaria outbreaks in the Horn of Africa. In 10 years, it has been detected as far east as Djibouti and as far west as Ghana. Early detections were mostly incidental, but now active surveillance in Africa has been updated to include An. stephensi. Morphological identification of An. stephensi from native vectors can be challenging, thus, sequence-based assays have been used to confirm identification during initial detections. Methods of sequence-based identification of An. stephensi have varied across initial detections to date. Here, we summarize initial detections, make suggestions that could provide a standardized approach, and discuss how sequences can inform additional genomic studies beyond species identification.

11.
12.
Front Plant Sci ; 15: 1385210, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721336

RESUMO

Understanding the genetic basis of local adaption is crucial in the context of global climate change. Mangroves, as salt-tolerant trees and shrubs in the intertidal zone of tropical and subtropical coastlines, are particularly vulnerable to climate change. Kandelia obovata, the most cold-tolerant mangrove species, has undergone ecological speciation from its cold-intolerant counterpart, Kandelia candel, with geographic separation by the South China Sea. In this study, we conducted whole-genome re-sequencing of K. obovata populations along China's southeast coast, to elucidate the genetic basis responsible for mangrove local adaptation to climate. Our analysis revealed a strong population structure among the three K. obovata populations, with complex demographic histories involving population expansion, bottleneck, and gene flow. Genome-wide scans unveiled pronounced patterns of selective sweeps in highly differentiated regions among pairwise populations, with stronger signatures observed in the northern populations compared to the southern population. Additionally, significant genotype-environment associations for temperature-related variables were identified, while no associations were detected for precipitation. A set of 39 high-confidence candidate genes underlying local adaptation of K. obovata were identified, which are distinct from genes under selection detected by comparison between K. obovata and its cold-intolerant relative K. candel. These results significantly contribute to our understanding of the genetic underpinnings of local adaptation in K. obovata and provide valuable insights into the evolutionary processes shaping the genetic diversity of mangrove populations in response to climate change.

13.
Genes Chromosomes Cancer ; 63(5): e23238, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722224

RESUMO

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well-characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA-targeted Next generation sequencing (NGS) panels (MSK-IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31-76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of TP53 (79%) and RB1 (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. CDKN2A deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in BCOR, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm-level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in TP53, RB1, and CDKN2A. Overall survival and progression-free survival of PRMS were significantly worse (p < 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.


Assuntos
Rabdomiossarcoma Embrionário , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Rabdomiossarcoma/classificação , Mutação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genômica/métodos , Biomarcadores Tumorais/genética , Proteínas de Ligação a Retinoblastoma/genética , Ubiquitina-Proteína Ligases
14.
Plant J ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722594

RESUMO

Brassica carinata (BBCC) commonly referred to as Ethiopian mustard is a natural allotetraploid containing the genomes of Brassica nigra (BB) and Brassica oleracea (CC). It is an oilseed crop endemic to the northeastern regions of Africa. Although it is under limited cultivation, B. carinata is valuable as it is resistant/highly tolerant to most of the pathogens affecting widely cultivated Brassica species of the U's triangle. We report a chromosome-scale genome assembly of B. carinata accession HC20 using long-read Oxford Nanopore sequencing and Bionano optical maps. The assembly has a scaffold N50 of ~39.8 Mb and covers ~1.11 Gb of the genome. We compared the long-read genome assemblies of the U's triangle species and found extensive gene collinearity between the diploids and allopolyploids with no evidence of major gene losses. Therefore, B. juncea (AABB), B. napus (AACC), and B. carinata can be regarded as strict allopolyploids. We cataloged the nucleotide-binding and leucine-rich repeat immune receptor (NLR) repertoire of B. carinata and, identified 465 NLRs, and compared these with the NLRs in the other Brassica species. We investigated the extent and nature of early-generation genomic interactions between the constituent genomes of B. carinata and B. juncea in interspecific crosses between the two species. Besides the expected recombination between the constituent B genomes, extensive homoeologous exchanges were observed between the A and C genomes. Interspecific crosses, therefore, can be used for transferring disease resistance from B. carinata to B. juncea and broadening the genetic base of the two allotetraploid species.

15.
mSystems ; : e0009524, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727215

RESUMO

The Solar Lake in Taba, Egypt, encompasses one of the few modern-day microbial mats' systems metabolically analogous to Precambrian stromatolites. Solar Lake benthic communities and their adaptation to the Lake's unique limnological cycle have not been described for over two decades. In this study, we revisit the flat mat and describe the summer's shallow water versus exposed microbial community; the latter occurs in response to the seasonal partial receding of water. We employed metagenomic NovaSeq-6000 shotgun sequencing and 16S rRNA, mcrA, and dsrB quantitative PCR. A total of 292 medium-to-high-quality metagenome-assembled genomes (MAGs) were reconstructed. At the structural level, Candidatus Aenigmatarchaeota, Micrarchaeota, and Omnitrophota MAGs were exclusively detected in the shallow-water mats, whereas Halobacteria and Myxococcota MAGs were specific to the exposed microbial mat. Functionally, genes involved in reactive oxygen species (ROS) detoxification and osmotic pressure were more abundant in the exposed than in the shallow-water microbial mats, whereas genes involved in sulfate reduction/oxidation and nitrogen fixation were ubiquitously detected. Genes involved in the utilization of methylated amines for methane production were predominant when compared with genes associated with alternative methanogenesis pathways. Solar Lake methanogen MAGs belonged to Methanosarcinia, Bathyarchaeia, Candidatus Methanofastidiosales, and Archaeoglobales. The latter had the genetic capacity for anaerobic methane oxidation. Moreover, Coleofasciculus chthonoplastes, previously reported to dominate the winter shallow-water flat mat, had a substantial presence in the summer. These findings reveal the taxonomic and biochemical microbial zonation of the exposed and shallow-water Solar Lake flat mat benthic community and their capacity to ecologically adapt to the summer water recession. IMPORTANCE: Fifty-five years ago, the extremophilic "Solar Lake" was discovered on the Red Sea shores, garnering microbiologists' interest worldwide from the 1970s to 1990s. Nevertheless, research on the lake paused at the turn of the millennium. In our study, we revisited the Solar Lake benthic community using a genome-centric approach and described the distinct microbial communities in the exposed versus shallow-water mat unveiling microbial zonation in the benthic communities surrounding the Solar Lake. Our findings highlighted the unique structural and functional adaptations employed by these microbial mat communities. Moreover, we report new methanogens and phototrophs, including an intriguing methanogen from the Archaeoglobales family. We describe how the Solar Lake's flat mat microbial community adapts to stressors like oxygen intrusion and drought due to summer water level changes, which provides insights into the genomic strategies of microbial communities to cope with altered and extreme environmental conditions.

16.
mSystems ; : e0022624, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727238

RESUMO

Staphylococcus epidermidis, a common commensal bacterium found on human skin, can cause infections in clinical settings, and the presence of antibiotic resistance genes (ARGs) impedes the treatment of S. epidermidis infections. However, studies characterizing the ARGs in S. epidermidis with regard to genomic and ecological diversities are limited. Thus, we performed a comprehensive and comparative analysis of 405 high-quality S. epidermidis genomes, including those of 35 environmental isolates from the Han River, to investigate the genomic diversity of antibiotic resistance in this pathogen. Comparative genomic analysis revealed the prevalence of ARGs in S. epidermidis genomes associated with multi-locus sequence types. The genes encoding dihydrofolate reductase (dfrC) and multidrug efflux pump (norA) were genome-wide core ARGs. ß-Lactam class ARGs were also highly prevalent in the S. epidermidis genomes, which was consistent with the resistance phenotype observed in river isolates. Furthermore, we identified chloramphenicol acetyltransferase genes (cat) in the plasmid-like sequences of the six river isolates, which have not been reported previously in S. epidermidis genomes. These genes were identical to those harbored by the Enterococcus faecium plasmids and associated with the insertion sequence 6 family transposases, homologous to those found in Staphylococcus aureus plasmids, suggesting the possibility of horizontal gene transfer between these Gram-positive pathogens. Comparison of the ARG and virulence factor profiles between S. epidermidis and S. aureus genomes revealed that these two species were clearly distinguished, suggesting genomic demarcation despite ecological overlap. Our findings provide a comprehensive understanding of the genomic diversity of antibiotic resistance in S. epidermidis. IMPORTANCE: A comprehensive understanding of the antibiotic resistance gene (ARG) profiles of the skin commensal bacterium and opportunistic pathogen Staphylococcus epidermidis needs to be documented from a genomic point of view. Our study encompasses a comparative analysis of entire S. epidermidis genomes from various habitats, including those of 35 environmental isolates from the Han River sequenced in this study. Our results shed light on the distribution and diversity of ARGs within different S. epidermidis multi-locus sequence types, providing valuable insights into the ecological and genetic factors associated with antibiotic resistance. A comparison between S. epidermidis and Staphylococcus aureus revealed marked differences in ARG and virulence factor profiles, despite their overlapping ecological niches.

17.
Mol Ecol Resour ; : e13967, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727721

RESUMO

Zoo populations of threatened species are a valuable resource for the restoration of wild populations. However, their small effective population size poses a risk to long-term viability, especially in species with high genetic load. Recent bioinformatic developments can identify harmful genetic variants in genome data. Here, we advance this approach, analysing the genetic load in the threatened pink pigeon (Nesoenas mayeri). We lifted the mutation-impact scores that had been calculated for the chicken (Gallus gallus) to estimate the genetic load in six pink pigeons. Additionally, we perform in silico crossings to predict the genetic load and realized load of potential offspring. We thus identify the optimal mate pairs that are theoretically expected to produce offspring with the least inbreeding depression. We use computer simulations to show how genomics-informed conservation can reduce the genetic load whilst reducing the loss of genome-wide diversity. Genomics-informed management is likely to become instrumental in maintaining the long-term viability of zoo populations.

18.
Front Genet ; 15: 1383609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706792

RESUMO

Background: In sub-Saharan Africa, 80% of poultry production is on smallholder village farms, where chickens are typically reared outdoors in free-ranging conditions. There is limited knowledge on chickens' phenotypic characteristics and genetics under these conditions. Objective: The present is a large-scale study set out to phenotypically characterise the performance of tropically adapted commercial chickens in typical smallholder farm conditions, and to examine the genetic profile of chicken phenotypes associated with growth, meat production, immunity, and survival. Methods: A total of 2,573 T451A dual-purpose Sasso chickens kept outdoors in emulated free-ranging conditions at the poultry facility of the International Livestock Research Institute in Addis Ababa, Ethiopia, were included in the study. The chickens were raised in five equally sized batches and were individually monitored and phenotyped from the age of 56 days for 8 weeks. Individual chicken data collected included weekly body weight, growth rate, body and breast meat weight at slaughter, Newcastle Disease Virus (NDV) titres and intestinal Immunoglobulin A (IgA) levels recorded at the beginning and the end of the period of study, and survival rate during the same period. Genotyping by sequencing was performed on all chickens using a low-coverage and imputation approach. Chicken phenotypes and genotypes were combined in genomic association analyses. Results: We discovered that the chickens were phenotypically diverse, with extensive variance levels observed in all traits. Batch number and sex of the chicken significantly affected the studied phenotypes. Following quality assurance, genotypes consisted of 2.9 million Single Nucleotide Polymorphism markers that were used in the genomic analyses. Results revealed a largely polygenic mode of genetic control of all phenotypic traits. Nevertheless, 15 distinct markers were identified that were significantly associated with growth, carcass traits, NDV titres, IgA levels, and chicken survival. These markers were located in regions harbouring relevant annotated genes. Conclusion: Results suggest that performance of chickens raised under smallholder farm conditions is amenable to genetic improvement and may inform selective breeding programmes for enhanced chicken productivity in sub-Saharan Africa.

19.
Mitochondrial DNA B Resour ; 9(5): 578-582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707210

RESUMO

Leibnitzia anandria is a perennial herbaceous plant with medicinal properties, and the entire plant can be used in traditional medicine. Leibnitzia anandria was once classified under the genus Gerbera Cass., but was reclassified under Leibnitzia Cass. recently. In this study, using the GeneLab M sequencing technology of the Genemind platform, we have sequenced, assembled, and analyzed the complete chloroplast genome of Leibnitzia anandria for the first time. The genome is 154168 bp in length, consisting of a large single-copy region(LSC, 80166 bp), a small single-copy region(SSC, 18202 bp), and a pair of inverted repeat sequences(IR, 27900 bp). We have predicted and annotated a total of 133 genes, including 88 protein-coding genes, 37 tRNA-coding genes, and 8 rRNA-coding genes. The results of the phylogenetic analysis indicate that Leibnitzia anandria and Leibnitzia nepalensis, as well as the closely related Gerbera plant, clustered into a separate clade, rather than grouping together with the other plants belonging to the tribe Mutisieae. This study provides new information for the phylogeny research of Leibnitzia anandria, contributing to a better understanding of its taxonomy and evolution.

20.
Heliyon ; 10(9): e30332, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707387

RESUMO

Cronobacter sakazakii is an opportunistic pathogen that has been associated with severe infection in neonates such as necrotizing enterocolitis (NEC), neonatal meningitis, and bacteremia. This pathogen can survive in a relatively dry environment, especially in powdered infant formula (PIF). Unfortunately, conventional drugs that were once effective against C. sakazakii are gradually losing their efficacy due to rising antibiotic resistance. In this study, a subtractive genomic approach was followed in order to identify potential therapeutic targets in the pathogen. The whole proteome of the pathogen was filtered through a step-by-step process, which involved removing paralogous proteins, human homologs, sequences that are less essential for survival, proteins with shared metabolic pathways, and proteins that are located in cells other than the cytoplasmic membrane. As a result, nine novel drug targets were identified. Further, the analysis also unveiled that the FDA-approved drug Terbinafine can be repurposed against the Glutathione/l-cysteine transport system ATP-binding/permease protein CydC of C. sakazakii. Moreover, molecular docking and dynamics studies of Terbinafine and CydC suggested that this drug can be used to treat C. sakazakii infection in neonates. However, for clinical purposes further in vitro and in vivo studies are necessary.

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