genetic diversity

遗传多样性
  • 文章类型: Journal Article
    广西的艾滋病病例和死亡率很高,这突显了研究该地区HIV-1遗传多样性对疾病进展的影响的紧迫性。2016年1月至2021年12月纳入初诊HIV-1患者,每半年进行一次随访和CD4+T淋巴细胞检测,直至2022年12月。采用多因素logistic回归分析治疗前CD4+T淋巴细胞计数的影响因素,同时采用局部加权回归模型(LOESS)和广义估计方程模型(GEE)评估影响CD4+T淋巴细胞恢复的因素。Cox回归分析用于检查亚型对生存风险的影响。此外,HIV-1env序列用于预测CXCR4和CCR5受体。该研究涵盖了1867个具有pol序列的个体和281个具有env序列的个体。我们的研究结果表明,年龄超过30岁,离婚/丧偶,农民,异性感染,CRF01_AE,长期感染,治疗前病毒载量>10000拷贝/ml是治疗前CD4+T淋巴细胞下降风险较高的相关因素。具体来说,男性,年龄超过30岁,异性感染(HET),长期感染,CRF01_AE,和治疗前CD4T细胞计数低于350/µL被确定为阻碍CD4+T淋巴细胞恢复的危险因素。与CRF07_BC和CRF55_01B相比,感染CRF01_AE的个体的治疗前CD4+T淋巴细胞计数和恢复较低。此外,CRF01_AE和CRF08_BC亚型的死亡率高于CRF07_BC,CRF55_01B,和其他亚型。值得注意的是,CRF01_AE显示最高百分比的CXCR4亲和力比。这项研究揭示了HIV-1基因多样性对CD4+T淋巴细胞动力学和临床结果的复杂影响。突出了广西艾滋病病毒感染的多面性,为该地区HIV感染者的亚型特异性疾病进展提供了新的见解。
    The high proportion of AIDS cases and mortality rates in Guangxi underscores the urgency to investigate the influence of HIV-1 genetic diversity on disease progression in this region. Newly diagnosed HIV-1 patients were enrolled from January 2016 to December 2021, and the follow-up work and detection of CD4+T lymphocytes were carried out every six months until December 2022. Multivariate logistic regression was used to analyze the factors affecting pre-treatment CD4+T lymphocyte counts, while local weighted regression models (LOESS) and generalized estimating equation models (GEE) were conducted to assess factors influencing CD4+T Lymphocyte Recovery. Cox regression analysis was utilized to examine the impact of subtypes on survival risk. Additionally, HIV-1 env sequences were utilized for predicting CXCR4 and CCR5 receptors. The study encompassed 1867 individuals with pol sequences and 281 with env sequences. Our findings indicate that age over 30, divorced/widowed, peasant, heterosexual infection, CRF01_AE, long-term infection, and Pre-treatment Viral load >10000 copies/ml were factors associated with higher risk for pre-treatment CD4+T lymphocyte decline. Specifically, male gender, age over 30, heterosexual infection (HETs), long-term infection, CRF01_AE, and Pre-treatment CD4 T cell counts below 350/µL were identified as risk factors impeding CD4+T lymphocyte recovery. Pre-treatment CD4+T lymphocyte counts and recovery in individuals infected with CRF01_AE were lower compared to CRF07_BC and CRF55_01B. Additionally, CRF01_AE and CRF08_BC subtypes exhibited higher mortality rates than CRF07_BC, CRF55_01B, and other subtypes. Notably, CRF01_AE demonstrated the highest percentage of CXCR4 affinity ratios. This research unveils the intricate influence of HIV-1 gene diversity on CD4+T lymphocyte dynamics and clinical outcomes. It highlights the multifaceted nature of HIV infection in Guangxi, providing novel insights into subtype-specific disease progression among HIV-infected individuals in this region.
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  • 文章类型: Journal Article
    尽管受威胁植物的非原位集合在它们包含最大遗传变异时最有用,收藏中遗传多样性的保护和维持通常鲜为人知。我们使用对Karomiagigas的非原位集合的群体基因组分析进行了案例研究,来自坦桑尼亚的极度濒危的热带树。在两个野生种群中只有约43个个体是已知的,并在两个地点从野生收集的种子中建立了包含34个个体的异地收集物。该研究旨在了解集合中代表了多少多样性,分析离境个体的亲子关系,并确定捕获和维持遗传多样性的有效策略。
    我们使用2b-RADseq方法对所有已知个体进行了基因分型,比较了野生种群和异地采集的遗传多样性,并对藏品进行了亲子关系分析。
    根据私有等位基因的数量,发现野生种群比离地种群具有更高的遗传多样性水平,多态位点的数量,观察到的和预期的杂合性,核苷酸多样性,和等位基因丰富度。此外,只有32.6%的野生个体在异地代表,许多个体被发现是单个野生个体自交的产物。
    群体基因组分析为K.gigas遗传多样性的保护提供了重要的见解,找出差距和低效率,但也强调了保护遗传多样性的策略。基因组分析提供了必要的信息,以确保馆藏有效地保护受威胁的热带树木的遗传多样性。
    UNASSIGNED: Although ex situ collections of threatened plants are most useful when they contain maximal genetic variation, the conservation and maintenance of genetic diversity in collections are often poorly known. We present a case study using population genomic analyses of an ex situ collection of Karomia gigas, a critically endangered tropical tree from Tanzania. Only ~43 individuals are known in two wild populations, and ex situ collections containing 34 individuals were established in two sites from wild-collected seed. The study aimed to understand how much diversity is represented in the collection, analyze the parentage of ex situ individuals, and identify efficient strategies to capture and maintain genetic diversity.
    UNASSIGNED: We genotyped all known individuals using a 2b-RADseq approach, compared genetic diversity in wild populations and ex situ collections, and conducted parentage analysis of the collections.
    UNASSIGNED: Wild populations were found to have greater levels of genetic diversity than ex situ populations as measured by number of private alleles, number of polymorphic sites, observed and expected heterozygosity, nucleotide diversity, and allelic richness. In addition, only 32.6% of wild individuals are represented ex situ and many individuals were found to be the product of selfing by a single wild individual.
    UNASSIGNED: Population genomic analyses provided important insights into the conservation of genetic diversity in K. gigas, identifying gaps and inefficiencies, but also highlighting strategies to conserve genetic diversity ex situ. Genomic analyses provide essential information to ensure that collections effectively conserve genetic diversity in threatened tropical trees.
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  • 文章类型: Journal Article
    来自O组的遗传上不同的HIV-1株(HIV-1非M)的易感性,N,和P到CCR5共受体拮抗剂,maraviroc(MVC),在45个临床菌株的大小组中进行了调查,病毒遗传多样性的代表。将结果与具有已知向性的HIV-1组M(HIV-1/M)的参考菌株进行比较。在非M菌株中,观察到对MVC的广泛表型敏感性。绝大多数HIV-1/O毒株(40/42)对MVC表现出很高的易感性,中值和平均IC50值为1.23和1.33nM,分别,与HIV-1/MR5株(1.89nM)相似。然而,剩下的两个HIV-1/O菌株表现出较低的易感性(IC50在482和496nM),根据他们的双重/混合(DM)取向。有趣的是,两种HIV-1/N菌株表现出不同的易感性模式,尽管总是具有相对较低的IC50值(2.87和47.5nM)。这强调了仅基于IC50值确定敏感性的复杂性。我们的研究检查了所有HIV-1非M组对MVC的易感性,并将这些发现与病毒嗜性(X4,R5或DM)相关联。结果证实了在感染HIV-1非M的患者开始MVC治疗之前确定向性的重要意义。此外,我们主张考虑额外的参数,例如抑制曲线的斜率,提供更全面的表型易感性特征。
    目的:与HIV-1M组不同,缺乏对HIV-1非M群体的研究(O,N,和P)在理解他们对抗逆转录病毒治疗的易感性方面提出了挑战,特别是由于它们对非核苷逆转录酶抑制剂的天然抗性。TROPI-CO研究在逻辑上补充了我们先前对整合酶抑制剂和抗gp120功效的研究。迄今为止存在的45种非M菌株的最大组产生了关于maraviroc(MVC)易感性的有价值的结果。MVCIC50的显著变化揭示了一系列的磁化率,大多数菌株表现出R5向性。值得注意的是,无MVC耐药菌株提示潜在的治疗途径.该研究还采用了强大的基于细胞的新型表型测定,并根据抑制曲线斜率确定了不同的磁化率。我们的发现强调了在启动MVC之前确定向性的重要性,并为在HIV-1非M感染的微妙背景下选择有效的治疗策略提供了重要的见解。
    The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from groups O, N, and P to the CCR5 co-receptor antagonist, maraviroc (MVC), was investigated among a large panel of 45 clinical strains, representative of the viral genetic diversity. The results were compared to the reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC were observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC, with median and mean IC50 values of 1.23 and 1.33 nM, respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the two remaining HIV-1/O strains exhibited a lower susceptibility (IC50 at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the two HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50 values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50 values. Our study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5, or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles.
    OBJECTIVE: Unlike HIV-1 group M, the scarcity of studies on HIV-1 non-M groups (O, N, and P) presents challenges in understanding their susceptibility to antiretroviral treatments, particularly due to their natural resistance to non-nucleoside reverse transcriptase inhibitors. The TROPI-CO study logically complements our prior investigations into integrase inhibitors and anti-gp120 efficacy. The largest panel of 45 non-M strains existing so far yielded valuable results on maraviroc (MVC) susceptibility. The significant variations in MVC IC50 reveal a spectrum of susceptibilities, with most strains displaying R5 tropism. Notably, the absence of MVC-resistant strains suggests a potential therapeutic avenue. The study also employs a robust novel cell-based phenotropism assay and identifies distinct groups of susceptibilities based on inhibition curve slopes. Our findings emphasize the importance of determining tropism before initiating MVC and provide crucial insights for selecting effective therapeutic strategies in the delicate context of HIV-1 non-M infections.
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  • 文章类型: Journal Article
    尽管以前有报道称出现了对唑类药物敏感性降低的马拉色菌,关于这种酵母菌的唑类抗性分离株的实际患病率和遗传多样性的信息有限.我们评估了在2年期间在兽医教学医院就诊的犬中耳炎或皮肤病病例中分离株的唑耐药率,并分析了ERG11(编码羊毛甾醇14-α脱甲基酶,唑类的主要靶标)和一组表现出唑类敏感性降低的分离株的全基因组序列多样性。来自54次临床发作(1-6次分离株/发作)的89株厚皮杆菌分离株的敏感性测试显示,对大多数唑类药物和其他抗真菌药的最低抑制浓度(MIC)较低,而是来自六个不同事件的11个分离株(即,12.4%的分离株和11.1%的发作)对多种唑类(氟康唑,伊曲康唑,酮康唑,泊沙康唑,ravukonazole,和/或伏立康唑)。ERG11对这11株耐药唑的分离株进行测序,鉴定出8个DNA序列图谱,其中大多数包含在一些唑敏感分离物中也发现的氨基酸取代。全基因组测序(WGS)结果显示,来自同一耳炎发作的唑类耐药分离株,甚至影响同一只动物的不同事件,与其他狗的分离株相比,它们之间的遗传相关性更高。总之,我们的结果证实了在先前的研究中观察到的动物来源的厚皮杆菌分离株中显著的ERG11序列变异性,并证明了WGS对该酵母菌属的流行病学研究的价值.
    我们分析了在一家兽医医院中分离的耐唑马拉色菌的流行率和多样性。发现多唑类耐药的患病率较低(约占分离株和病例的10%)。抗性分离株的全基因组和ERG11测序揭示了显着的遗传多样性。
    Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from the same episode of otitis, or even different episodes affecting the same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrated the value of WGS for disentangling the epidemiology of this yeast species.
    We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.
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  • 文章类型: Journal Article
    结核分枝杆菌复合体(MTBC)菌株的遗传多样性在Amhara地区的圣水场所(HWS)出现肺结核(PTB)症状的个体中进行了表征,埃塞俄比亚。
    从2019年6月至2020年3月进行了一项横断面研究,以描述MTBC分离株的遗传多样性和耐药性。收集痰标本并在Löwenstein-Jensen培养基中培养。线探针测定,MTBDRplusVER2.0和MTBDRslVER2.0用于检测一线和二线抗TB药物抗性模式。利用spoligotyping技术来表征遗传多样性。使用STATA15进行统计分析。
    在560名有PTB症状的参与者中,122例(21.8%)为培养阳性病例。116个分离株的Spoligotyping揭示了不同的MTBC亚谱系,有四个主要谱系:欧美(EA)(谱系4),东非印第安人(EAI)(谱系3),埃塞俄比亚(ETH)(谱系7),东亚(EA)(谱系2)。大多数(96.6%)的分离株是EA(谱系4)和EAI,比例分别为54.3%和42.2%,分别。总共确定了31种spoligotype模式,其中26个记录在SITVIT2数据库中。其中,有15种独特的spoligotypes,而11个被分组为2-17个分离株。SIT149/T3-ETH(n=17),SIT26/CAS1-DELHI(n=16),SIT25/CAS1-DELHI(n=12),以SIT52/T2(n=11)为主。一种罕见的spoligotype模式:SIT41/土耳其和SIT1/北京,在北谢瓦也被确认。具有已知SIT的子谱系的总体聚类率为76.4%。在测试的122株培养阳性菌株中,16.4%对利福平(RIF)和/或异烟肼(异烟肼)耐药。在12.3%的分离株中检测到耐多药结核病(MDR-TB),其中五种是氟喹诺酮类药物(FLQs)耐药。SIT149/T3-ETH和SIT21/CAS1-KILI亚谱系显示较高比例的耐药性。
    确定了不同的MTBCspoligotypes,以T和CAS家族和EA(谱系4)为主。耐药结核病的高流行率,SIT149/T3-ETH和CAS1-KILI子谱系占更大份额,被观察到。在本研究队列中,有必要进行大样本量和具有更强鉴别力的测序方法的研究,以更好地了解循环MTBC的遗传多样性。这将有助于采取有针对性的干预措施。
    UNASSIGNED: The genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia.
    UNASSIGNED: A cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Löwenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first-and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15.
    UNASSIGNED: Of 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%.Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance.
    UNASSIGNED: Diverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.
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  • 文章类型: Journal Article
    绵羊饲养员要求美国绵羊实验站(USSES)通过国家绵羊改良计划(NSIP)参与国家遗传评估。原因包括需要(1)比较工业和美国农业部(USDA)的生产率,(2)美国农业部鸡群的透明度,(3)NSIP的遗传联系,通过对行业群体进行抽样,(4)开发供公开发布的优质遗传系。作为回应,USSES开始将来自NSIP参与羊群的外部父亲纳入USSESTarghee羊群。我们的目标,根据谱系分析,是为了测试外部遗传学是否渗入羊群。谱系包括13189只平均最大世代的动物,意味着完整的世代,和平均等效完整代分别为4.2、1.8和2.6。平均世代间隔为3.1年。参考种群定义为2021年至2023年出生的羔羊(n=792)。另外两个种群被定义为当前的成熟母羊群(n=123)和当前的成熟公羊群(n=14)。整个种群的遗传保护指数平均为7.7,参考种群为25.7。整个种群的总体近亲繁殖为0.003,参考种群为0.006。近交率为每代0.0003。整个人群的平均亲缘关系为0.015,参考人群的平均亲缘关系为0.018。创始人的有效数量,祖先的有效数量,对参考人群有贡献的创始人基因组当量分别为60,39和19.1.创始人的有效数量与祖先的有效数量之比为1.5,表明存在遗传瓶颈。有效人口规模的度量范围为102至547。在外来父亲产生的704个后代中,保留了17只公羊和132只母羊用于繁殖。USSES父亲产生了299个后代,其中保留了2只公羊羔羊和51只母羊羔羊。合并外部父系导致参考人群的外部遗传学的遗传方差的累积百分比为48.8、49.1和44.2,当前成熟的母羊群,和目前成熟的公羊,分别。利益相关者的需求通过外部父亲的渗入和参与NSIP来解决,但是未来的选择实践需要进行修改,以保持羊群中至少50%的USSES核心遗传学。
    Sheep breeders requested that the U.S. Sheep Experiment Station (USSES) to participate in national genetic evaluation through the National Sheep Improvement Program (NSIP). The reasons included the need for (1) a comparison of the productivity of industry and United States Department of Agriculture (USDA) lines, (2) transparency of USDA flocks, (3) genetic ties for NSIP by sampling of industry flocks, and (4) development of premium genetic lines for public release. In response, USSES began to incorporate external sires from NSIP participating flocks into the USSES Targhee flock. Our objective, based on a pedigree analysis, was to test if introgression of external genetics into the flock was achieved. The pedigree included 13,189 animals with mean maximum generations, mean complete generations, and mean equivalent complete generations of 4.2, 1.8, and 2.6, respectively. The mean generation interval was 3.1 yr. The reference population was defined as lambs born from 2021 to 2023 (n = 792). Two additional populations were defined as the current mature ewe flock (n = 123) and the current mature rams (n = 14). The Genetic Conservation Index averaged 7.7 for the full population and 25.7 for the reference population. Overall inbreeding was 0.003 for the full population and 0.006 for the reference population. The rate of inbreeding was 0.0003 per generation. Average relatedness was 0.015 for the full population and 0.018 for the reference population. The effective number of founders, effective number of ancestors, and founder genome equivalents contributing to the reference population were 60, 39, and 19.1, respectively. The ratio of the effective number of founders to the effective number of ancestors was 1.5, indicating the presence of genetic bottlenecks. Measures of effective population size ranged from 102 to 547. Of the 704 offspring produced by external sires, 17 ram lambs and 132 ewe lambs were retained for breeding. The USSES sires produced 299 offspring with 2 ram lambs and 51 ewe lambs retained. Incorporating external sires resulted in a cumulative percentage of genetic variance of 48.8, 49.1, and 44.2 of external genetics for the reference population, current mature ewe flock, and current mature rams, respectively. Stakeholder needs were addressed by introgression of external sires and participation in NSIP, but future selection practices need to be modified to maintain a minimum of 50% USSES core genetics in the flock.
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  • 文章类型: Preprint
    将人类癌症组织异种移植到小鼠体内以测试新的癌症治疗方法对于理解和治疗这种疾病至关重要。然而,只有少数近交系小鼠被用来研究癌症,以及主要是一种菌株的衍生物,主要是NOD/ShiLtJ,用于治疗效果研究。正如已经证明的那样,当人类癌细胞系或患者来源的组织(PDX)被异种移植到小鼠体内时,例如,肿瘤细胞是人的,但包含肿瘤(基质)的支持细胞来自小鼠。因此,异种移植组织的研究结果受宿主菌株的影响。我们以前发表过,当相同的肿瘤细胞异种移植到不同的小鼠品系中时,肿瘤生长的模式,肿瘤的组织学,浸润肿瘤的免疫细胞数量,循环细胞因子的类型因菌株而异。因此,为了更好地理解癌症在体内的行为,必须异种移植多个小鼠品系。在这里,我们描述并报告了一系列方法,我们用来揭示相同癌细胞系时表达的基因和蛋白质,MDA-MB-231在不同的宿主中异种移植。首先,使用蛋白质组学分析,我们展示了如何在体内使用相同的细胞系来揭示肿瘤细胞中有助于其适应宿主的蛋白质变化。然后,我们展示了不同的宿主对同一细胞系的分子反应。我们还发现,使用多种菌株可以揭示比传统上用于“难以异种移植”PDX的宿主更合适的宿主。此外,利用复杂的性状遗传学,我们说明了发现支持肿瘤生长的宿主等位基因的可行方法。最后,我们证明了多样性远交小鼠,小鼠品系遗传多样性模型的缩影,可以使用2-脱氧-D-葡萄糖处理与人细胞系或PDX异种移植。
    Xenografting human cancer tissues into mice to test new cures against cancers is critical for understanding and treating the disease. However, only a few inbred strains of mice are used to study cancers, and derivatives of mainly one strain, mostly NOD/ShiLtJ, are used for therapy efficacy studies. As it has been demonstrated when human cancer cell lines or patient-derived tissues (PDX) are xenografted into mice, the neoplastic cells are human but the supporting cells that comprise the tumor (the stroma) are from the mouse. Therefore, results of studies of xenografted tissues are influenced by the host strain. We previously published that when the same neoplastic cells are xenografted into different mouse strains, the pattern of tumor growth, histology of the tumor, number of immune cells infiltrating the tumor, and types of circulating cytokines differ depending on the strain. Therefore, to better comprehend the behavior of cancer in vivo, one must xenograft multiple mouse strains. Here we describe and report a series of methods that we used to reveal the genes and proteins expressed when the same cancer cell line, MDA-MB-231, is xenografted in different hosts. First, using proteomic analysis, we show how to use the same cell line in vivo to reveal the protein changes in the neoplastic cell that help it adapt to its host. Then, we show how different hosts respond molecularly to the same cell line. We also find that using multiple strains can reveal a more suitable host than those traditionally used for a \"difficult to xenograft\" PDX. In addition, using complex trait genetics, we illustrate a feasible method for uncovering the alleles of the host that support tumor growth. Finally, we demonstrate that Diversity Outbred mice, the epitome of a model of mouse-strain genetic diversity, can be xenografted with human cell lines or PDX using 2-deoxy-D-glucose treatment.
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  • 文章类型: Editorial
    非洲科学有巨大的潜力,然而,它努力应对重大挑战。在这里,我们描述了在尤贝州建立生物医学科学研究和培训中心(BioRTC),尼日利亚东北部,作为促进大陆研究的枢纽的案例研究,并描述了克服当前障碍的策略。我们详细介绍了建立BioRTC的步骤,强调利益相关者参与的至关重要性,社区参与,资源优化和合作。凭借其最先进的设施和对培训非洲科学家的承诺,BioRTC有望大大推进该地区的神经科学研究和培训。虽然我们正处于旅程的早期阶段,我们的模型,强调开放获取和包容性,为类似资源有限的环境中的神经科学研究发展提供了可复制的蓝图,承诺丰富全球神经科学界。我们邀请那些分享我们愿景并相信我们潜力的人的支持与合作。
    African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research and Training Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to overcome current barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation and collaborations. With its state-of-the-art facilities and commitment to training African scientists, BioRTC is poised to significantly advance neuroscience research and training in the region. Although we are in the early stages of our journey, our model, emphasizing open access and inclusivity, offers a replicable blueprint for neuroscience research development in similar resource-limited settings, promising to enrich the global neuroscience community. We invite the support and collaboration of those who share our vision and believe in our potential.
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  • 文章类型: Journal Article
    Poultry meat contaminated with Campylobacter, a major bacterial cause of foodborne gastroenteritis worldwide, is considered the primary source of human campylobacteriosis. Thus, reduction or elimination of Campylobacter in poultry production will have a significant impact on food safety and public health. Despite the significant progress made over the last decades, many puzzles remain about the epidemiology of Campylobacter on poultry farms, hampering the development of an effective control strategy. This longitudinal study was conducted to determine the prevalence and genetic diversity of Campylobacter in a U.S. commercial broiler production farm system. Cecal contents (15 samples/flock) and boot swabs (3 samples/flock) were collected from approximately 6-wk-old birds from 406 conventional broiler flocks reared in 53 houses on 15 farms (located within a relatively close geographic proximity and managed by the same poultry integrator) for up to eight consecutive production cycles and cultured for Campylobacter. Pulsed-field gel electrophoresis was used to investigate the genetic diversity of the Campylobacter jejuni isolates recovered from the cecal contents. The prevalence of Campylobacter at the farm, house, and flock levels were found to be 93% (14/15), 79% (42/53), and 47% (192/406), respectively. Campylobacter prevalence varied remarkably among different farms and flocks, with some farms or houses testing consistently negative while others being positive all the time over the entire study period. Campylobacter isolation rate changed significantly by sample type (higher by cecal contents vs. boot swabs) and season/production cycle (higher in spring vs. other seasons). The majority (88%; 2364/2675) of the isolates were identified as C. jejuni, and almost all the rest (11%; 303/2675) were Campylobacter coli. Genotyping showed limited diversity within a flock and suggested persistence of some C. jejuni clones over multiple production cycles on the same farm. In conclusion, this study indicated that although Campylobacter prevalence was overall high, there were marked differences in the prevalence among the broiler flocks or farms tested. Future studies aimed at identification of potential risk factors associated with differential Campylobacter status are warranted in order to develop effective on-farm interventions.
    Estudio longitudinal sobre Campylobacter en parvadas comerciales de pollo de engorde criados convencionalmente en los Estados Unidos: prevalencia y diversidad genética. Los productos cárnicos de origen avícola contaminado con Campylobacter, que es una importante causa bacteriana de gastroenteritis transmitida por alimentos en todo el mundo, se consideran la principal fuente de campilobacteriosis humana. Por lo tanto, la reducción o eliminación de Campylobacter en la producción avícola tendrá un impacto significativo en la seguridad alimentaria y en la salud pública. A pesar de los importantes avances realizados en las últimas décadas, persisten muchos enigmas sobre la epidemiología de Campylobacter en las granjas avícolas, lo que obstaculiza el desarrollo de una estrategia de control eficaz. Este estudio longitudinal se realizó para determinar la prevalencia y la diversidad genética de Campylobacter en un sistema de granja de producción comercial de pollos de engorde en los Estados Unidos. Se recogieron contenidos cecales (15 muestras/parvada) y cubre botas de arrastre (tres muestras/parvada) de aves de aproximadamente seis semanas de edad de 406 parvadas de pollos de engorde convencionales criadas en 53 casetas de 15 granjas (ubicadas dentro de una proximidad geográfica relativamente cercana y manejadas por el mismo integrador avícola) durante ocho ciclos de producción consecutivos y con cultivo para Campylobacter. Se utilizó electroforesis en gel de campo con pulsasiones para investigar la diversidad genética de los aislados de Campylobacter jejuni recuperados del contenido cecal. Se encontró que la prevalencia de Campylobacter a nivel de granja, caseta y parvada era del 93% (14/15), 79% (42/53) y 47% (192/406), respectivamente. La prevalencia de Campylobacter varió notablemente entre diferentes granjas y rebaños, y algunas granjas o casetas dieron resultados consistentemente negativos mientras que otras dieron positivo todo el tiempo durante todo el período del estudio. La tasa de aislamiento de Campylobacter cambió significativamente según el tipo de muestra (mayor con muestras de contenido cecal en comparación con los cubre botas de arrastre) y la estación/ciclo de producción (mayor en primavera frente a otras estaciones). La mayoría (88%; 2364/2675) de los aislados se identificaron como C. jejuni, y casi todo el resto (11%; 303/2675) fueron Campylobacter coli. La genotipificación mostró una diversidad limitada dentro de una parvada y sugirió la persistencia de algunos clones de C. jejuni durante múltiples ciclos de producción en la misma granja. En conclusión, este estudio indicó que, aunque la prevalencia de Campylobacter fue alta en general, hubo marcadas diferencias en la prevalencia entre las parvadas o granjas de pollos de engorde analizadas. Se justifica la conducción de estudios futuros destinados a identificar posibles factores de riesgo asociados con el estado diferencial de Campylobacter para desarrollar intervenciones efectivas en las granjas.
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  • 文章类型: Journal Article
    背景:杜鹃花,于2020年在贵州省普定县首次发现,已适应生活在岩石裂隙栖息地,具有重要的观赏和经济价值。然而,该物种的遗传多样性和种群结构很少被描述,严重影响野生种质资源的收集和保护。
    结果:在本研究中,使用13对多态性微卫星引物研究了来自六个不同地理种群的65个R.pudingense种质的遗传多样性。总共获得254个等位基因(Na),每个基因座平均19.5个等位基因。多态信息含量(PIC)的平均值,观测杂合性(Ho),和期望杂合度(He)分别为0.8826、0.4501和0.8993,这些结果表明所采用的微卫星引物具有良好的多态性,普丁安斯在物种水平上表现出很高的遗传多样性。平均遗传分化系数(Fst)为0.1325,表明普丁香种群发生了中度分歧。群体间遗传分化系数和基因流量的平均值分别为0.1165和3.1281。分子方差分析(AMOVA)表明,大多数种群差异(88%)归因于种群内变异。PCoA结果与UPGMA聚类分析的结果一致,支持R.pudingense的六个种群可以清楚地分为两个单独的集群的结论。根据Mantel分析,我们推测PD人群可能已经从WM-1和WM-2迁移。因此,建议尽可能保护普丁恩斯的自然栖息地,以最大限度地保护其遗传多样性。
    结论:这是对贵州省普定势的遗传多样性和种群结构的首次综合分析。研究结果表明,该园艺植物具有较高的遗传多样性和中等的种群差异。本研究为普丁香野生资源的保护提供了理论依据,为该新品种的选育或培育奠定了基础。
    BACKGROUND: Rhododendron pudingense, firstly discovered in Puding county of Guizhou province in 2020, have adapted to living in rocky fissure habitat, which has important ornamental and economic values. However, the genetic diversity and population structure of this species have been rarely described, which seriously affects the collection and protection of wild germplasm resources.
    RESULTS: In the present study, 13 pairs of primers for polymorphic microsatellite were used to investigate the genetic diversity of 65 R. pudingense accessions from six different geographic populations. A total of 254 alleles (Na) were obtained with an average of 19.5 alleles per locus. The average values of polymorphic information content (PIC), observed heterozygosity (Ho), and expected heterozygosity (He) were 0.8826, 0.4501, and 0.8993, respectively, These results indicate that the microsatellite primers adopted demonstrate good polymorphism, and the R. pudingense exhibits a high level of genetic diversity at the species level. The average genetic differentiation coefficient (Fst) was 0.1325, suggested that moderate divergence occurred in R. pudingense populations. The average values of genetic differentiation coefficient and gene flow among populations were 0.1165 and 3.1281, respectively. The analysis of molecular variance (AMOVA) indicated that most of the population differences (88%) were attributed to within-population variation. The PCoA results are consistent with the findings of the UPGMA clustering analysis, supporting the conclusion that the six populations of R. pudingense can be clearly grouped into two separate clusters. Based on Mantel analysis, we speculate that the PD population may have migrated from WM-1 and WM-2. Therefore, it is advised to protect the natural habitat of R. pudingense in situ as much as possible, in order to maximize the preservation of its genetic diversity.
    CONCLUSIONS: This is the first comprehensive analysis of genetic diversity and population structure of R. pudingense in Guizhou province. The research results revealed the high genetic diversity and moderate population diferentiation in this horticulture plant. This study provide a theoretical basis for the conservation of wild resources of the R. pudingense and lay the foundation for the breeding or cultivation of this new species.
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