Integrating phylogenetic and ecological distances reveals new insights into parasite host specificity

The range of hosts a pathogen infects (host specificity) is a key element of disease risk that may be influenced by both shared phylogenetic history and shared ecological attributes of prospective hosts. Phylospecificity indices quantify host specificity in terms of host relatedness, but can fail to capture ecological attributes that increase susceptibility. For instance, similarity in habitat niche may expose phylogenetically unrelated host species to similar pathogen assemblages. Using a recently proposed method that integrates multiple distances, we assess the relative contributions of host phylogenetic and functional distances to pathogen host specificity (functional–phylogenetic host specificity). We apply this index to a data set of avian malaria parasite (Plasmodium and Haemoproteus spp.) infections from Melanesian birds to show that multihost parasites generally use hosts that are closely related, not hosts with similar habitat niches. We also show that host community phylogenetic ß‐diversity (Pßd) predicts parasite Pßd and that individual host species carry phylogenetically clustered Haemoproteus parasite assemblages. Our findings were robust to phylogenetic uncertainty, and suggest that phylogenetic ancestry of both hosts and parasites plays important roles in driving avian malaria host specificity and community assembly. However, restricting host specificity analyses to either recent or historical timescales identified notable exceptions, including a ‘habitat specialist’ parasite that infects a diversity of unrelated host species with similar habitat niches. This work highlights that integrating ecological and phylogenetic distances provides a powerful approach to better understand drivers of pathogen host specificity and community assembly.     

Describing the role of Drosophila melanogaster ABC transporters in insecticide biology using CRISPR-Cas9 knockouts

ABC transporters have a well-established role in drug resistance, effluxing xenobiotics from cells and tissues within the organism. More recently, research has been dedicated to understanding the role insect ABC transporters play in insecticide toxicity, but progress in understanding the contribution of specific transporters has been hampered by the lack of functional genetic tools. Here, we report knockouts of three Drosophila melanogaster ABC transporter genes, Mdr49, Mdr50, and Mdr65, that are homologous to the well-studied mammalian ABCB1 (P-glycoprotein). Each knockout mutant was created in the same wild type background and tested against a panel of insecticides representing different chemical classes. Mdr65 knockouts were more susceptible to all neuroactive insecticides tested, but Mdr49 and Mdr50 knockouts showed increased susceptibility or resistance depending on the insecticide used. Mdr65 was chosen for further analysis. Calculation of LC₅₀ values for the Mdr65 knockout allowed the substrate specificity of this transporter to be examined. No obvious distinguishing structural features were shared among MDR65 substrates. A role for Mdr65 in insecticide transport was confirmed by testing the capacity of the knockout to synergize with the ABC inhibitor verapamil and by measuring the levels of insecticide retained in the body of knockout flies. These data unambiguously establish the influence of ABC transporters on the capacity of wild type D. melanogaster to tolerate insecticide exposure and suggest that both tissue and substrate specificity underpin this capacity.     

不同负重量站立30 min对健康青年心脏自主神经功能的影响

目的：本研究评估不同负重量（0 kg、27.5 kg和50 kg）站立30 min对心脏自主神经功能的影响。方法：采用随机交互设计,24名健康男性受试者完成3次30 min静止站立,分别记录RR间期：包括安静状态5 min（卧位）,静态站立30 min,站立后恢复期5 min（卧位）,进行相应心率变异（HRV）分析。结果：与安静状态相比,站立中HR增加（P < 0.05）,RMSSD降低（P < 0.05）,负重量增加,SDNN、SDNN/HR和LF呈下降趋势,HF降低（P < 0.05）,LF/HF增加（P < 0.05）。与负重0 kg和27.5 kg相比,负重50 kg E-POCPeak和TRIMP增加（P < 0.05）。恢复期,HR下降,但未能恢复至安静水平;RMSSD恢复至安静水平,SDNN增加（P < 0.05）;负重50 kg,HR均高于负重0 kg和27.5 kg（P < 0.05）。结论：急性静力性30 min站立,心脏自主神经功能发生调整,随着负重量增加,整体HRV呈下降趋势,5 min恢复期,交感神经活性处在较高水平。不同负重状态下整体HRV变化相似。     

TiD: Standalone software for mining putative drug targets from bacterial proteome

TiD is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. With an input bacterial proteome, TiD removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. The targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. TiD classifies proposed targets as known, novel and virulent. Users can perform pathway analysis, choke point analysis, interactome analysis, subcellular localization and functional annotations through web servers cross-referenced with the application. Drug targets identified by TiD for Listeria monocytogenes, Bacillus anthracis and Pseudomonas aeruginosa have revealed significant overlaps with previous studies. TiD takes < 2 h to scan putative targets from a bacterial proteome with ~ 5000 proteins; hence, we propose it as a useful tool for rational drug design. TiD is available at http://bmicnip.in/TiD/.     

A meta‐analysis on growth,physiological, and biochemical responses of woody species to ground‐level ozone highlights the role of plant functional types

The carbon‐sink strength of temperate and boreal forests at midlatitudes of the northern hemisphere is decreased by ozone pollution, but knowledge on subtropical evergreen broadleaved forests is missing. Taking the dataset from Chinese studies covering temperate and subtropical regions, effects of elevated ozone concentration ([O₃]) on growth, biomass, and functional leaf traits of different types of woody plants were quantitatively evaluated by meta‐analysis. Elevated mean [O₃] of 116 ppb reduced total biomass of woody plants by 14% compared with control (mean [O₃] of 21 ppb). Temperate species from China were more sensitive to O₃ than those from Europe and North America in terms of photosynthesis and transpiration. Significant reductions in chlorophyll content, chlorophyll fluorescence parameters, and ascorbate peroxidase induced significant injury to photosynthesis and growth (height and diameter). Importantly, subtropical species were significantly less sensitive to O₃ than temperate ones, whereas deciduous broadleaf species were significantly more sensitive than evergreen broadleaf and needle‐leaf species. These findings suggest that carbon‐sink strength of Chinese forests is reduced by present and future [O₃] relative to control (20–40 ppb). Given that (sub)‐tropical evergreen broadleaved species dominate in Chinese forests, estimation of the global carbon‐sink constraints due to [O₃] should be re‐evaluated.     

Exploring the Ca2+-dependent synaptic dynamics in vibro-dissociated cells

Dynamic alteration of the synaptic strength is one of the most important processes occurring in the nervous system. Combination of electrophysiology, confocal imaging and molecular biology led to significant advances in this research field. Yet, a progress in this area, in particular in studies of changes in the quantal behavior of central synapses and impact of glial cells on individual synapses, is hampered by technical difficulties of resolving small quantal synaptic currents. In this paper we will show how the technique of non-enzymatic vibro-dissociation, which enables to isolate living neurons avoiding artifacts of cell culture and preserving functional synapse, can be used to obtain a valuable information on fine details and mechanisms of synaptic plasticity. In particular, we will describe our recent results on Ca²⁺-dependent modulation of the postsynaptic AMPA and NMDA receptors in the individual synaptic boutons.     

腹腔镜下行子宫切除术及淋巴清扫术治疗老年子宫颈癌的疗效

目的:探讨腹腔镜与开腹下行子宫切除术及淋巴清扫术治疗老年子宫颈癌患者的临床疗效。方法:选取2014年1月至2016年1月我院收治的60例老年子宫颈癌患者,随机分为两组,每组30例,A组患者接受开放性子宫切除术及淋巴清扫术,B组患者在腹腔镜下行子宫切除术及淋巴清扫术,比较两组患者的手术情况、术后恢复情况以及术中、术后并发症的发生情况和随访期间的生活质量。结果:B组患者手术中淋巴结的清扫数目明显比A组多(P0.05),术中出血量和术后使用镇痛泵的次数明显少于A组(P0.05),抗生素的使用时间、术后排气时间、膀胱功能恢复时间、引流管滞留时间、住院时间较A组患者明显缩短(P0.05),术中大出血以及术后尿潴留、淋巴囊肿的发生率显著低于A组(P0.05);术后3个月和6个月的I-QOL以及FACT-G评分显著高于A组(P0.05)。结论:腹腔镜下行子宫切除术加盆腔淋巴清扫术治疗老年子宫颈癌患者的临床疗效显著,有利于患者术后恢复,并有效提高患者术后生活质量。     

TLIF与PLIF对退行性腰椎滑脱合并腰椎管狭窄患者临床疗效及安全性比较

目的:比较经椎间孔椎体间融合术(transforaminal lumbar interbody fusion,TLIF)与经后路椎体间融合术(posterior lumbar interbody fusion,PLIF)对退行性腰椎滑脱合并腰椎管狭窄患者临床疗效及安全性。方法:选择2013年6月到2015年6月我院收治的90例退行性腰椎滑脱合并腰椎管狭窄患者,随机分为TLIF组和PLIF组,各45例。TLIF组患者给予TLIF治疗,PLIF组患者给予PLIF治疗。记录并比较两组患者手术时间、术中失血量、术后引流量及术后卧床时间。评价并比较两组患者治疗前后视觉疼痛评分(visual analogue scale,VAS)和Oswestry功能不良指数(oswestry disability index,ODI)。记录并比较两组患者治疗后神经根损伤、感染、硬膜囊破裂等并发症发生情况。结果:TLIF组患者的手术时间、术中失血量、术后引流量及术后卧床时间均明显小于PLIF组,均具有显著性差异(P0.05)。治疗前,两组患者VAS、ODI评分,相比均无显著性差异(P0.05);治疗后,两组患者VAS、ODI评分均明显小于治疗前,且TLIF组患者的VAS、ODI评分均明显小于PLIF组,均具有显著性差异(P0.05)。TLIF组患者的并发症发生率明显低于PLIF组,均具有显著性差异(X~2=3.873,P=0.049)。结论:相比于PLIF,TLIF治疗退行性腰椎滑脱合并腰椎管狭窄患者的临床疗效显著,有助于腰椎功能的恢复,并发症发生率较低,值得在临床上推广应用。