A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet–Biedl syndrome in a Pakistani family

Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family.     

鸡减蛋综合征病毒（EDSV—76）末端前体蛋白的基因结构分析

从中国发病鸡群中分离的鸡减蛋综合征病毒弱毒株ＡＡ－２,经常规方法提取其病毒核酸后,组建了完整的限制性内切酶ＰｓｔＩ及ＨｉｎｇⅢ水解片段的基因文库,并对其中ＨｉｎｄⅢ,－ＳａｃⅠ进行了序列测定。同源比较分析证明：其Ｌ链含编码病毒末端前体蛋白,容量为５８０个氨基酸残基的开放读码框架。     

Swimming with the giant: coexistence patterns of a new redfin minnow Pseudobarbus skeltoni from a global biodiversity hot spot

Ecological niche theory predicts that coexistence is facilitated by resource partitioning mechanisms that are influenced by abiotic and biotic interactions. Alternative hypotheses suggest that under certain conditions, species may become phenotypically similar and functionally equivalent, which invokes the possibility of other mechanisms, such as habitat filtering processes. To test these hypotheses, we examined the coexistence of the giant redfin Pseudobarbus skeltoni, a newly described freshwater fish, together with its congener Pseudobabus burchelli and an anabantid Sandelia capensis by assessing their scenopoetic and bionomic patterns. We found high habitat and isotope niche overlaps between the two redfins, rendering niche partitioning a less plausible sole mechanism that drives their coexistence. By comparison, environment–trait relationships revealed differences in species–environment relationships, making habitat filtering and functional equivalence less likely alternatives. Based on P. skeltoni's high habitat niche overlap with other species, and its large isotope niche width, we inferred the likelihood of differential resource utilization at trophic level as an alternative mechanism that distinguished it from its congener. In comparison, its congener P. burchelli appeared to have a relatively small trophic niche, suggesting that its trophic niche was more conserved despite being the most abundant species. By contrast, S. capensis was distinguished by occupying a higher trophic position and by having a trophic niche that had a low probability of overlapping onto those of redfins. Therefore, trophic niche partitioning appeared to influence the coexistence between S. capensis and redfins. This study suggests that coexistence of these fishes appears to be promoted by their differences in niche adaptation mechanisms that are probably shaped by historic evolutionary and ecological processes.     

血管生成素样蛋白4和Ⅱ型肺泡细胞表面抗原-6与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能研究

摘要 目的：分析血管生成素样蛋白4(ANGPTL4)和Ⅱ型肺泡细胞表面抗原-6(KL-6)与急性呼吸窘迫综合征严重程度的关系及对预后的评估效能。方法：选择我院自2020年1月至2022年12月收治的120例急性呼吸窘迫综合征患者作为研究对象（观察组）,根据氧合指数（PaO₂/FiO₂）分为轻度组、中度组和重度组;另选120例非急性呼吸窘迫综合征患者作为对照组。检测所有患者血清ANGPTL4和KL-6的表达水平,分析血清ANGPTL4和KL-6与APACHE Ⅱ评分、PaO₂/FiO₂的关系,使用受试者工作特征曲线（ROC）下面积（AUC）评价血清ANGPTL4联合KL-6对急性呼吸窘迫综合征预后的评估效能。结果：对比对照组,观察组血清ANGPTL4、KL-6的表达水平均明显升高（P＜0.05）;血清ANGPTL4、KL-6的表达水平在轻度组、中度组和重度组中差异有统计学意义,且急性呼吸窘迫综合征越严重,升高越明显（P＜0.05）;经Pearson相关性分析,急性呼吸窘迫综合征患者血清ANGPTL4、KL-6的表达水平与PaO₂/FiO₂呈负相关,与APACHE Ⅱ评分呈正相关（P＜0.05）;经ROC曲线分析,血清ANGPTL4联合KL-6预测急性呼吸窘迫综合征患者入院28d内死亡的敏感度为90.14%、特异度为65.74%,AUC为0.900。结论：血清ANGPTL4、KL-6表达水平升高与急性呼吸窘迫综合征严重程度增大密切相关,两者联合在患者预后评估中具有一定价值,可作为判断病情及预后的辅助指标。     

学龄前阻塞性睡眠呼吸暂停低通气综合征儿童肠道菌群特征分析

摘要 目的：探讨学龄前阻塞性睡眠呼吸暂停低通气综合征（OSAHS）儿童与正常儿童肠道菌群的差异。方法：选取2023年7月至2023年11月期间新疆医科大学第一附属医院儿科门诊收治的学龄前OSAHS儿童30例作为OSAHS组,选取同期于新疆医科大学第一附属医院健康管理中心体检健康的儿童30例作为对照组。利用16SrDNA扩增子测序技术对肠道菌群进行分析。采用Spearman法分析睡眠质量与肠道菌群门、属水平丰度的相关性。结果：OSAHS组和对照组共发现2588个扩增子序列变异（ASVs）,OSAHS组检出特有ASVs 1034个,对照组检出特有ASVs 1554个。OSAHS组Chao1指数和Observed otus指数显著低于对照组（P<0.05）,两组间Shannnon指数、Simpson指数、Goods coverage指数、Peilou-e指数均差异无统计学意义（P>0.05）。OSAHS组与对照组间肠道菌群群落结构存在显著差异（P<0.05）。在门水平上,OSAHS组拟杆菌门的相对丰度低于对照组,厚壁菌门的相对丰度、厚壁菌门/拟杆菌门的比例高于对照组（P<0.05）。在属水平上,OSAHS组与对照组组优势菌群相对分度比较差异无统计学意义（P>0.05）。在门水平上,睡眠质量与拟杆菌门呈正相关（P<0.05）。在属水平上,睡眠质量与双歧杆菌属、乳杆菌属呈负相关,与拟杆菌属呈正相关（P<0.05）。阻塞性呼吸暂停低通气指数（OAHI）与肠杆菌属呈负相关（P<0.05）。最低血氧饱和度（LSaO₂）与肠杆菌属呈正相关（P<0.05）。平均血氧饱和度（MSaO₂）与X.Eubacterium._eligens_group呈正相关（P＜0.05）。结论：与正常儿童的肠道菌群的种类和相对丰度相比,学龄前OSAHS儿童的厚壁菌门/拟杆菌门比例升高,可能存在肠道菌群失调。睡眠质量在门、属水平上与拟杆菌门、双歧杆菌属、乳杆菌属明显相关。     

Histoplasmosis diseminada y síndrome hemofagocítico en pacientes VIH: serie de casos en un hospital peruano

BackgroundDisseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality.AimsTo describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV.MethodsA retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015.ResultsDH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%.ConclusionsIn this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy.     

Extracellular HIV-1 Nef increases migration of monocytes

Infiltration of human immunodeficiency virus type 1 (HIV-1)-infected and uninfected monocytes/macrophages in organs and tissues is a general phenomenon observed in progression of acquired immunodeficiency syndrome (AIDS). HIV-1 protein Nef is considered as a progression factor in AIDS, and is released from HIV-1-infected cells. Here, we show that extracellular Nef increases migration of monocytes. This effect is (i) concentration-dependent, (ii) reaches the order of magnitude of that induced by formyl-methyonyl-leucyl-proline (fMLP) or CC chemokine ligand 2 (CCL2)/monocyte chemotactic protein (MCP)-1, (iii) inhibited by anti-Nef monoclonal antibodies as well as by heating, and (iv) depends on a concentration gradient of Nef. Further, Nef does not elicit monocytic THP-1 cells to express chemokines such as CCL2, macrophage inhibitory protein-1alpha (CCL3) and macrophage inhibitory protein-1beta (CCL4). These data suggest that extracellular Nef may contribute to disease progression as well as HIV-1 spreading through affecting migration of monocytes.     

Pathology of Hematodinium infections in snow crabs (Chionoecetes opilio) from Newfoundland, Canada

Bitter crab disease (BCD) of snow crabs, Chionoecetes opilio, is caused by a parasitic dinoflagellate, Hematodinium sp. The disease has shown an alarming increase in prevalence in the commercial fishery in eastern and northeastern areas of Newfoundland and Labrador since it was first recorded there in the early 1990s. We documented histopathological alterations to the tissues in snow crabs with heavy infections of Hematodinium sp. and during sporulation of the parasite. Pressure necrosis was evident in the spongy connective tissues of the hepatopancreas and the blood vessels in most organs. In heavy infections, little remained of the spongy connective tissues around the hepatopancreas. Damage to the gills varied; in some cases it was severe, particularly during sporulation, involving apparent thinning of the cuticle, loss of epithelial cells, and fusion of the membranous layers of adjacent gill lamellae. Affected lamellae exhibited varying degrees of distention with a loss of trabecular cells, hemocyte infiltrations, and swelling or "clubbing" along the distal margins. Large numbers of zoospores were located along the distal margins of affected lamellae suggesting that sporulation may cause a lysis or bursting of the thin lamellar cuticle, releasing spores. Pressure necrosis, due to the build up of high densities of parasites, was the primary histopathological alteration in most tissues. Hematodinium infections in the snow crab are chronic, long-term infections that end in host death, during sporulation of the parasite.     

Structural and spectroscopic studies of a model for catechol oxidase

A binuclear copper complex, [Cu₂(BPMP)(OAc)₂][ClO₄]·H₂O, has been prepared using the binucleating ligand 2,6-bis[bis(pyridin-2-ylmethylamino)methyl]-4-methylphenol (H-BPMP). The X-ray crystal structure reveals the copper centers to have a five-coordinate square pyramidal geometry, with the acetate ligands bound terminally. The bridging phenolate occupies the apical position of the square-based pyramids and magnetic susceptibility, electron paramagnetic resonance (EPR) and variable-temperature variable-field magnetic circular dichroism (MCD) measurements indicate that the two centers are very weakly antiferromagnetically coupled (J = −0.6 cm⁻¹). Simulation of the dipole–dipole-coupled EPR spectrum showed that in solution the Cu–O–Cu angle was increased from 126° to 160° and that the internuclear distance was larger than that observed crystallographically. The high-resolution spectroscopic information obtained has been correlated with a detailed ligand-field analysis to gain insight into the electronic structure of the complex. Symmetry arguments have been used to demonstrate that the sign of the MCD is characteristic of the tetragonally elongated environment. The complex also displays catecholase activity (k _cat = 15 ± 1.5 min⁻¹, K _M = 6.4 ± 1.8 mM), which is compared with other dicopper catechol oxidase models. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.