AB

糖尿病
  • 文章类型: Journal Article
    斑马鱼是评估基因参与小儿白内障的杰出模型。通过操纵斑马鱼胚胎的基因组并比较突变后代与野生型胚胎的表型,可以增强白内障的基因发现。然而,野生型实验室鱼也会患上白内障,可能会混淆结果。在这项研究中,我们比较了两种常用的野生型实验室菌株之间的基线白内障率,AB和TL,还有mCherry记者的近交转基因系。我们评估了受精后4天鱼的白内障的总共805个镜头图像,并将观察到的每个白内障评分为轻度,中度或重度。我们发现AB菌株的白内障率为16.2%,TL有8.9%,mCherry占0.7%,这些比率有显著差异。我们发现,TL菌株的轻度白内障发生率低于AB鱼,然而,AB和TL菌株中中度和重度表型的比率相似。总的来说,我们发现,基线白内障率在单个设施中的菌株之间存在显著差异,并得出结论,在计划评估白内障遗传原因的实验时,应评估基线白内障率.
    Zebrafish are an outstanding model for assessing the involvement of genes in paediatric cataracts. Gene discovery for cataracts is enhanced by manipulation of the genome of zebrafish embryos and comparing the phenotypes of mutant progeny with the wildtype embryos. However, wildtype laboratory fish can also develop cataracts, potentially confounding the results. In this study, we compared the baseline cataract rate between two commonly used wildtype laboratory strains, AB and TL, and also an outbred transgenic line with mCherry reporter. We assessed a total of 805 lens images of fish at 4 days post-fertilisation for cataracts and scored each cataract observed as mild, moderate or severe. We found that the AB strain had a cataract rate of 16.2%, TL had 8.9%, and mCherry had 0.7% and these rates were significantly different. We found that TL strain had a lower rate of mild cataracts than AB fish, however, the rate of moderate and severe phenotypes in the AB and the TL strain was similar. Overall, we showed that the baseline cataract rate varies significantly between the strains housed in a single facility and conclude that baseline rates of cataracts should be assessed when planning experiments to assess the genetic causes of cataracts.
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  • 文章类型: Journal Article
    2022/2023年,欧洲经历了连续第三个高致病性禽流感季节。在此期间,捷克共和国再次受到严重影响。第一次,扑杀鸟类的数量接近一百万只,这是前几季的三倍。在家禽爆发的同时,还观察到海鸥大量死亡。在本研究中,我们对2022/2023年在捷克共和国收集的137株H5N1病毒株进行了全基因组测序和系统发育分析(占所有疫情或地点的94.6%).分析揭示了四种不同的基因型:AB,CH,BB和AF。系统发育分析表明,AF基因型从上一个H5N1季节持续存在,没有重新分类。此外,基因型BB,主要在海鸥中检测到,在当地表现出明显的菌株多样性。该病毒还导致了商业饲养火鸡的一次爆发。最后,一个有趣的时空集群,具有三个共同循环的H5N1基因型,AB,CH和AF,没有发现B型重分类的证据。高度敏感的分子监测以及及时共享基因组序列和相关元数据可以极大地帮助跟踪传播和检测与这种潜在的人畜共患病原体的毒力增加相关的分子变化。
    In 2022/2023, Europe experienced its third consecutive season of high-pathogenicity avian influenza. During this period, the Czech Republic was again severely affected. For the first time, the number of culled birds approached one million, which was three times higher than in previous seasons. In parallel to the outbreaks in poultry, mass die-offs of gulls were also observed. In the present study, we performed whole-genome sequencing and phylogenetic analysis of 137 H5N1 strains collected in the Czech Republic in 2022/2023 (94.6% of all outbreaks or locations). The analysis revealed four distinct genotypes: AB, CH, BB and AF. Phylogenetic analysis suggested that the AF genotype persisted from the previous H5N1 season without reassortment. In addition, the genotype BB, which was detected mainly in gulls, showed a noticeable strain diversity at the local level. This virus was also responsible for a single outbreak in commercially bred turkeys. Finally, an interesting spatio-temporal cluster with three co-circulating H5N1 genotypes, AB, CH and AF, was identified with no evidence of intrasubtype reassortment. Highly sensitive molecular surveillance and the timely sharing of genomic sequences and associated metadata could greatly assist in tracking the spread and detecting molecular changes associated with the increased virulence of this potentially zoonotic pathogen.
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  • 文章类型: Case Reports
    在心脏移植前和心脏移植后作为常规测定进行HLAAb分析,以鉴定针对HLA的Ab,移植后的焦点集中在供体特异性的那些Ab上。虽然虚拟交叉匹配在许多情况下降低了对前瞻性交叉匹配的要求,心脏移植候补名单上的高度敏感儿童的管理仍然具有挑战性,并且可能会延迟成功识别合适器官的能力。
    本报告描述了连续列出用于移植的家族性限制性心肌病的同卵双胞胎男孩的组织相容性评估和管理。这些男孩接受了HLAAb测试,证明了广泛的泛DR反应性,包括针对SAgs的Ab。
    我们的团队在列出第一个孩子后不久就开始调查最初的Ab结果;兄弟在8天后被列出,并且具有相同的广泛Ab概况。临床实验室使用具有已知抗原分型的供体样品进行了多次调查交叉匹配,并继续观察到广泛的反应性。然后,我们与一个附属研究实验室合作,在那里我们确定了两个男孩中针对波形蛋白和波形蛋白阳性外泌体的高水平Abs。
    虽然已经描述了针对自身抗原波形蛋白的Abs会导致假阳性组织交叉匹配,这是首次报道这些Abs与使用固相分析的假阳性Ab筛选相关.这一发现为我们对这两个脆弱的儿科心脏移植候选人的管理和监测提供了依据。
    HLA Ab analysis is carried out as a routine assay both pre- and post-heart transplantation to identify Abs directed against HLA with a focus post-transplant on those Abs that are donor-specific. While virtual crossmatching has decreased the requirement for prospective crossmatching in many cases, the management of highly sensitized children on the heart transplant waitlist remains challenging and can delay the ability to successfully identify a suitable organ.
    This report describes the histocompatibility assessment and management of identical twin boys with familial restrictive cardiomyopathy serially listed for transplant. The boys presented with HLA Ab testing that demonstrated broad pan-DR reactivity which included Abs directed against SAgs.
    Our team began investigating the initial Ab results soon after listing the first child; the brother was listed 8 days later and had the same broad Ab profile. The clinical lab ran multiple investigative crossmatches using donor samples with known antigen typing and continued to see broad reactivity. We then partnered with an affiliated research lab where we identified high-level Abs directed against vimentin along with vimentin-positive exosomes in both boys.
    While Abs directed against the self-antigen vimentin has been described to cause false-positive tissue crossmatches, this is the first report of these Abs being associated with false-positive Ab screens using solid-phase assays. This finding informed our management and surveillance in these two vulnerable pediatric heart transplant candidates.
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  • 文章类型: Journal Article
    对不同野生型斑马鱼(Daniorerio)的免疫谱的多样性知之甚少,尽管它作为研究人类疾病和药物测试的动物模型越来越受欢迎。在模拟人类疾病产生的数据的情况下,在解释结果时,很少考虑Danio鱼类的背景差异,这可能是有问题的,因为许多研究甚至没有提到动物的来源和菌株。在这项研究中,我们假设不同的野生型斑马鱼菌株可以呈现不同的免疫特性。为了解决两种常用的野生型斑马鱼菌株之间的免疫反应差异,AB和图宾根(TU),我们使用2,4,6-三硝基苯磺酸(TNBS)诱导的肠道炎症模型,并对这两种菌株的易感性和免疫谱进行了表征。我们的数据表明,当暴露于TNBS时,AB和TU菌株之间的存活率存在显着差异,提示这些菌株如何应对炎症挑战的重要生理差异。我们观察到AB菌株的死亡率增加,中性粒细胞较高的肠道浸润,当暴露于TNBS时,杯状细胞数量减少,IL-10表达减少,与TU菌株相比。总之,我们的研究证明了AB和TU动物的菌株特异性免疫反应。最后,这里显示的与菌株相关的炎症易感性的显著差异和免疫谱的差异,强调在利用斑马鱼模拟疾病和药物筛选目的时,需要考虑每个菌株的背景,因此,对斑马鱼的不同野生型菌株进行更好的免疫鉴定势在必行。
    Little is known about the diversity in immune profile of the different wild type strains of zebrafish (Danio rerio), despite its growing popularity as an animal model to study human diseases and drug testing. In the case of data resulting from modeling human diseases, differences in the background Danio fishes have rarely been taken into consideration when interpreting results and this is potentially problematic, as many studies not even mention the source and strain of the animals. In this study, we hypothesized that different wild type zebrafish strains could present distinct immune traits. To address the differences in immune responses between two commonly used wild type strains of zebrafish, AB and Tübingen (TU), we used an intestinal inflammation model induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) and characterized the susceptibility and immune profile in these two strains. Our data demonstrates significant differences in survival between AB and TU strains when exposed to TNBS, suggesting important physiological differences in how these strains respond to inflammatory challenges. We observed that the AB strain presented increased mortality, higher neutrophilic intestinal infiltration, decreased goblet cell numbers and decreased IL-10 expression when exposed to TNBS, compared to the TU strain. In summary, our study demonstrates strain-specific immunological responses in AB and TU animals. Finally, the significant variations in strain-related susceptibility to inflammation and the differences in the immune profile shown here, highlight that the background of each strain need to be considered when utilizing zebrafish to model diseases and for drug screening purposes, thus better immune characterization of the diverse wild type strains of zebrafish is imperative.
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  • 文章类型: Practice Guideline
    慢性乙型肝炎病毒(HBV)感染的诊断,感染的初始分期以及对治疗和未治疗患者的监测主要基于临床,生物学和影像学标准允许对大多数患者进行完整的非侵入性管理。除了传统的病毒学工具,HBVDNA的快速诊断测试和印迹纸测试是经过验证的替代方法。诊断后,最初的工作应该包括艾滋病毒,HCV和HDV血清学,HBeAg状态,和HBsAg和HBVDNA定量。严重程度(炎症和纤维化)的评估是基于ALT血清水平和通过弹性成像或血液测试肝纤维化的非侵入性评估,必须使用特定的截止值谨慎解释,并考虑ALT水平。一起来看,这些参数允许疾病分类和治疗决策。在非肝硬化患者中,每六个月通过超声筛查肝细胞癌的决定可能很困难,并且鼓励使用风险评分,例如PAGE-B。慢性HBV感染通常具有动态且通常不可预测的概况,并且定期监测是强制性的。在未经治疗的患者中,定期(3-12个月)随访应包括ALT和HBVDNA血清水平。定期HBsAg定量和肝纤维化的非侵入性评估可以改善疾病的预后和预后。在接受治疗的患者中,检查疗效主要基于HBVDNA阴性。在晚期纤维化患者中,肝脏硬度的演变可用于门静脉高压症的评估,但其改善不应被认为是停止肝细胞癌筛查。最后,新参数(HBVRNA,HBcrAg)很有前途,但它们的使用仍受到限制。
    Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cut-offs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
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  • 文章类型: Journal Article
    背景:对于运动员来说,由于在重大比赛中的压力,他们的表现出现了故障,这一直是一个问题。注意模式的改变和负性情感(NA)引起的应激反应(SR)的出现是对运动员成绩影响较大的直接原因。探讨如何改善运动员在紧张环境下的注意力偏差(AB)和SR是一个热门话题。
    目的:本研究旨在分析视觉搜索任务(VST)训练对压力情况下运动员AB和SR的改善效果。
    方法:将沈阳体育学院62名国家2级以上男子篮球运动员分为实验组(EG)和对照组(CG)。在EG中使用了视觉搜索任务训练程序(快乐,悲伤,恶心,中性面孔)和假训练计划用于CG(所有具有中性表情的面孔)两个月。在压力的情况下,对所有受试者训练前后的注意力行为进行了测试。采用生理一致性和自主平衡系统同步记录心率变异性。并行频域分析被划分为极低频带(VLF),低频(LF),高频(HF)和总频谱(TP)。归一化处理获得的指标如HFnorm,LFnorm,LF/HF。采取e-prime2.0软件获得注意力偏向得分。训练前后采用积极和消极情感量表(PANAS)和压力自评量表进行评估。
    结果:两组自评压力均低于训练前,试验组压力低于对照组(P<0.05)。培训后,实验组的积极情绪高于对照组,EG低于CG(P<0.05)。培训后,EG中快乐和中性面孔的注意力偏向得分高于CG,悲伤和厌恶面孔的注意偏向得分低于CG(P<0.05)。培训后,EG的LF/HF和LFnorm低于CG,HFnorm高于CG(P<0.05)。
    结论:视觉搜索任务训练能有效提高运动员PA和AB的阳性信息,减少负面信息和心理压力的关注偏差,解除SR。
    BACKGROUND: it has always been a problem for athletes that their performance is out of order due to pressure in major competitions. The change of attention pattern and the emergence of stress response (SR) caused by negative affect (NA) are the direct reasons for the greater impact on the performance of athletes. It is a hot topic to explore how to improve attention bias (AB) and SR of athletes in stressful situations.
    OBJECTIVE: the study aimed to analyze the improvement effect of visual search task (VST) training on AB and SR of athletes under pressure situations.
    METHODS: 62 male basketball players with national level 2 or above of Shenyang sports institute were divided into experimental group (EG) and control group (CG). Visual search task training program was used in the EG (happy, sad, disgusted, neutral faces) and sham training program was used in the CG (all faces with neutral expression) for two months. Under the stress situation, attention behavior of all subjects before and after training was tested. Physiological coherence and autonomic balance system were used to record heart rate variability synchronously. Parallel frequency domain analysis was divided into very low frequency band (VLF), low frequency (LF), high frequency (HF) and total spectrum (TP). The normalized treatment obtained indexes such as HFnorm, LFnorm, and LF/HF. The e-prime 2.0 software was adopted to obtain the attention bias score. The Positive and Negative Affect Scale (PANAS) and the self-rating stress scale were adopted for evaluation before and after training.
    RESULTS: the self-rating pressure in the two groups was lower than that before the training, and the pressure in the experimental group was lower than that in the control group (P < 0.05). After training, the positive emotion of the experimental group was higher than that of the control group, and the EG was lower than that of the CG (P < 0.05). After training, the score of attention bias of happy and neutral faces in the EG was higher than that of theCG, while the score of attention bias of sad and disgusted faces was lower than that of the CG (P < 0.05). After training, LF/HF and LFnorm in the EG were lower than those in the CG, and HFnorm was higher than those in the CG (P < 0.05).
    CONCLUSIONS: the training of visual search task can effectively improve the athletes\' PA and AB of positive information, reduce the attention bias of negative information and psychological pressure, and relieve theSR.
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  • 文章类型: Journal Article
    Viral RNAs (either derived from DNA viruses and genomic/mRNAs of RNA viruses) produced and replicated in eukaryotic cells are exposed to the activity of host cell RNA modification machinery. Moreover, some complex viruses encode their own RNA modification enzymes, generally cap-related m7G-and 2\'-O-methyltransferases whose expression allows specific modification of viral transcripts and modulation of viral RNA recognition by host restriction systems. Here we review current achievements in the detection of viral RNA modifications by liquid chromatography coupled to mass spectrometry (LC-MS) and deep sequencing-based approaches. The presence, origin and characterized functions of RNA modifications in viral RNAs are discussed.
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  • 文章类型: Comparative Study
    我们用了猪,流感的大型天然宿主动物,与人类有许多生理相似性,为了表征αβ,γδT细胞和抗体(Ab)对2009年大流行H1N1病毒感染的免疫反应。我们评估了具有相同MHC(猪白细胞抗原)的近交Babraham猪的病毒感染动力学和相关反应,并将其与商业近交动物进行了比较。高水平的鼻病毒脱落持续到感染后第4至5天,随后在第9天病毒急剧下降和清除。适应性T细胞和Ab应答在感染后5至6天可检测到,在9至14天达到峰值。γδT细胞在感染后第2天离体产生细胞因子,而从感染后第7天检测到产生病毒反应性IFNγ的γδT细胞。血液中NP四聚体特异性和病毒特异性CD8和CD4T细胞的分析,肺,肺引流淋巴结,和支气管肺泡灌洗(BAL)显示这些组织之间细胞因子产生的明显差异。BAL含有最高度活化的CD8,CD4和γδT细胞,产生大量的细胞因子,这可能有助于消除病毒。血液中的弱反应不能反映出强大的局部肺免疫反应。H1N1pdm09流感感染后,Babraham猪的免疫反应与近交动物的免疫反应相当。一起利用这两种猪模型的能力将提供无与伦比的能力来分析对流感的免疫反应。
    We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to days 4 to 5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from days 5 to 6 post infection reaching a peak at 9 to 14 days. γδ T cells produced cytokines ex vivo at day 2 post infection, while virus reactive IFNγ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes, and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4, and γδ T cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyze immune responses to influenza.
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  • 文章类型: Journal Article
    The spleen is a complex secondary lymphoid organ that plays a crucial role in controlling blood-stage infection with Plasmodium parasites. It is tasked with sensing and removing parasitized RBCs, erythropoiesis, the activation and differentiation of adaptive immune cells, and the development of protective immunity, all in the face of an intense inflammatory environment. This paper describes how these processes are regulated following infection and recognizes the gaps in our current knowledge, highlighting recent insights from human infections and mouse models.
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  • 文章类型: Case Reports
    红斑是一种与热相关的皮肤状况,可继发于与热持续直接或间接接触。历史上,红斑与壁炉和炉子的暴露有关;最近,它与加热器有关,热水瓶,和笔记本电脑。一名48岁的女性参加了色素沉着过度的评估,她腿远端有网状黄斑病变.其他病史显示,她在工作时在办公桌下使用空间加热器后出现了红斑。随着病原体的去除,她的皮肤状况停止了进展。除了红斑之外,与热相关的皮肤疾病包括基底细胞癌和鳞状细胞癌,烧伤,红血球痛,荨麻疹的亚型,和紫外线相关的疾病。对热相关皮肤状况的认识使临床医生能够根据相关的病史建立适当的诊断,皮肤病变的形态,and,如有必要,与皮肤状况的皮肤活检结果相关。
    Erythema ab igne is a thermal-associated skin condition that can occur secondary to persistent direct or indirect contact with heat. Historically, erythema ab igne has been linked to fireplace and stove exposures; more recently, it has been associated with heaters, hot water bottles, and laptops. A 48-year-old woman presented for the evaluation of hyperpigmented, reticulated macular lesions on her distal legs. Additional history revealed that she had developed erythema ab igne secondary to the use of a space heater underneath her desk at work. Her skin condition stopped progressing with removal of the causative agent. In addition to erythema ab igne, heat-related skin conditions include basal cell carcinomas and squamous cell carcinomas, burns, erythromelalgia, subtypes of urticaria, and ultraviolet-associated disorders. Awareness of thermal-associated skin conditions enables the clinician to establish the appropriate diagnosis based on the associated history of the condition, the morphology of the skin lesion, and, if necessary, correlation with the skin biopsy findings of the cutaneous condition.
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