Patent Human Infections with the Whipworm,Trichuris trichiura,Are Not Associated with Alterations in the Faecal Microbiota

Background

The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals.

Materials and Methods

School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes.

Results

Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition.

Discussion

Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies.     

Enteropathogens associated with acute diarrhea in community and hospital patients in Jakarta,Indonesia

The prevalence of bacteria, parasite and viral pathogens in 3875 patients with diarrhea in community and hospital settings from March 1997 through August 1999 in Jakarta, Indonesia was determined using routine bacteriology and molecular assay techniques. Bacterial pathogens isolated from hospital patients were, in decreasing frequency, Vibrio cholerae O1, Shigella flexneri, Salmonella spp. and Campylobacter jejuni, while S. flexneri, V. cholerae O1, Salmonella spp. and C. jejuni were isolated from the community patients. V. cholerae O1 was isolated more frequently (P<0.005) from the hospital patients than the community patients. Overall, bacterial pathogens were isolated from 538 of 3875 (14%) enrolled cases of diarrhea. Enterotoxigenic Escherichia coli were detected in 218 (18%) of 1244 rectal swabs. A small percentage of enterohemorrhagic E. coli (1%) and of Clostridium difficile (1.3%) was detected. Parasitic examination of 389 samples resulted in 43 (11%) positives comprising Ascaris lumbricoides (1.5%), Blastocystis hominis (5.7%), Giardia lamblia (0.8%), Trichuris trichiura (2.1%) and Endolimax nana (0.5%). Rotavirus (37.5%), adenovirus (3.3%) and Norwalk-like virus (17.6%) were also detected. Antimicrobial resistance was observed among some isolates. Bacterial isolates were susceptible to quinolones, with the exception of some isolates of C. jejuni which were resistant to ciprofloxacin, nalidixic acid and norfloxacin. Data obtained from this community- and hospital-based study will enable the Indonesian Ministry of Health to plan relevant studies on diarrheal diseases in the archipelago.     

Persistence of Swidden Cultivation in the Face of Globalization: A Case Study from Communities in Calakmul, Mexico

Over the last decades, political, economic and environmental pressures have encouraged changes from swidden to more intensive agricultural practices, resulting in the hypothesis that swidden cultivation systems are disappearing. In Calakmul, southeastern Mexico, communities decreased the area under milpa, the traditional maize swidden system, but a collapse did not occur. To document and explain the persistence of swidden we employ a variety of data: (1) 59 standardized household surveys from 2003 and 2010 in five villages, (2) in-depth interviews in one village, and (3) coupled human–environmental timelines in this same village. Droughts, hurricanes, and remittances were important drivers of decreases in milpa cultivation. Market crop profitability and conservation programs were also reported to affect the area under milpa. Off-farm employment and governmental transfers have tended to stabilize household economies and decrease dependency on agricultural production, but have also allowed households to maintain their milpas for subsistence and cultural reproduction. Findings in Calakmul point to the need to consider swidden as an evolving and active response to changing policy, economic, and environmental conditions.     

Changes in Antimicrobial Susceptibility of Native Enterococcus faecium in Chickens Fed Virginiamycin

The extent of transfer of antimicrobial resistance from agricultural environments to humans is controversial. To assess the potential hazard posed by streptogramin use in food animals, this study evaluated the effect of virginiamycin exposure on antimicrobial resistance in Enterococcus faecium recovered from treated broilers. Four consecutive broiler feeding trials were conducted using animals raised on common litter. In the first three trials, one group of birds was fed virginiamycin continuously in feed at 20 g/ton, and a second group served as the nontreated control. In the fourth trial, antimicrobial-free feed was given to both groups. Fecal samples were cultured 1 day after chickens hatched and then at 1, 3, 5, and 7 weeks of age. Isolates from each time point were tested for susceptibility to a panel of different antimicrobials. Quinupristin/dalfopristin-resistant E. faecium appeared after 5 weeks of treatment in trial 1 and within 7 days of trials 2 to 4. Following removal of virginiamycin in trial 4, no resistant isolates were detected after 5 weeks. PCR failed to detect vat, vgb, or erm(B) in any of the streptogramin-resistant E. faecium isolates, whereas the msr(C) gene was detected in 97% of resistant isolates. In an experimental setting using broiler chickens, continuous virginiamycin exposure was required to maintain a stable streptogramin-resistant population of E. faecium in the animals. The bases of resistance could not be explained by known genetic determinants.     

Synthesis of monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside for epitope mapping of anti-Candida albicans antibodies

A panel of six complementary monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside (1) were synthesized by stereoselective glycosylation of monodeoxy and mono-O-methyl monosaccharide acceptors with a 2-O-acetyl-glucosyl trichloroacetimidate donor, followed by a two-step oxidation-reduction sequence at C-2′. The β-manno configurations of the final deprotected congeners 2-7 were confirmed by measurement of ¹J_C1,H1 heteronuclear and ³J_1′,2′ homonuclear coupling constants. These disaccharide derivatives will be used to map the protective epitope recognized by a protective anti-Candida albicans monoclonal antibody C3.1 (IgG3) and to determine its key polar contacts with the binding site.     

Dipeptidyl nitrile inhibitors of Cathepsin L

A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.     

A new long-necked ‘sauropod-mimic’ stegosaur and the evolution of the plated dinosaurs

Stegosaurian dinosaurs have a quadrupedal stance, short forelimbs, short necks, and are generally considered to be low browsers. A new stegosaur, Miragaia longicollum gen. et sp. nov., from the Late Jurassic of Portugal, has a neck comprising at least 17 cervical vertebrae. This is eight additional cervical vertebrae when compared with the ancestral condition seen in basal ornithischians such as Scutellosaurus. Miragaia has a higher cervical count than most of the iconically long-necked sauropod dinosaurs. Long neck length has been achieved by ‘cervicalization’ of anterior dorsal vertebrae and probable lengthening of centra. All these anatomical features are evolutionarily convergent with those exhibited in the necks of sauropod dinosaurs. Miragaia longicollum is based upon a partial articulated skeleton, and includes the only known cranial remains from any European stegosaur. A well-resolved phylogeny supports a new clade that unites Miragaia and Dacentrurus as the sister group to Stegosaurus; this new topology challenges the common view of Dacentrurus as a basal stegosaur.     

Leptin increases maternal investment

The primary goal of virtually all organisms is to produce genetic offspring, thereby passing on their genes to future generations. Offspring production, however, is limited by available resources within an environment. Moreover, distributing sufficient energy among competing physiological systems is challenging and can result in trade-offs between self-maintenance and offspring investment when resources are limited. In the current study, we tested the hypothesis that the adipose hormone leptin is involved in mediating energetic trade-offs between competing physiological systems. Specifically, we tested the effects of elevated maternal leptin on investment into offspring production versus self maintenance (immune function), in the Siberian hamster (Phodopus sungorus). The current study provides the first evidence that leptin serves as a signal to mothers of available energy resulting in epigenetic effects. Therefore, elevated leptin allows females to retain more embryos to parturition, and rear more offspring to weaning via reduced maternal infanticide. Innate immune response was suppressed seemingly as a result of these enlarged litters, suggesting that the observed fitness increase is not without costs to the mother. Collectively, these findings suggest that leptin plays a critical role in allowing mothers to determine how much energy to invest in the production and care of young versus self-maintenance.     

记河北省后城组新发现之小型兽脚类足迹(英文)

几十年前人们就已经开始研究中国东北侏罗纪—白垩纪界线附近地层中的小型兽脚类恐龙足迹,虽然这些遗迹化石比辽宁省义县组带羽毛的恐龙及其他实体化石逊色了许多。本文记述了河北省承德南双庙后城组(土城子组)最下部河流相沉积中发现的一组兽脚类恐龙足迹。南双庙足迹具有三趾,趾粗大,其形态与美国下侏罗统经典的"brontozoid"足迹(Gral- lator,Anchisauripus和Eubrontes)相符。虽然许多产自辽宁土城子组中基本同时的brontozoid足迹被鉴定为小型的跷脚龙足迹属(Grallator),但南双庙足迹更大一些(全长可达28.8 cm),可能应该归入安琪龙足迹属(Anchisauripus)。南双庙足迹很可能是一群小型兽脚类行走而产生。在辽宁义县组的兽脚类恐龙中,最可能留下这类足迹的是小型的窃蛋龙类——尾羽龙(Caudipteryx)。不过这个解释还很勉强,因为这些足迹缺乏鉴定性特征,而且河北的后城组与辽宁的义县组之间还有一定的时间及地理间隔。     

The Structure of the Bacterial Oxidoreductase Enzyme DsbA in Complex with a Peptide Reveals a Basis for Substrate Specificity in the Catalytic Cycle of DsbA Enzymes

Oxidative protein folding in Gram-negative bacteria results in the formation of disulfide bonds between pairs of cysteine residues. This is a multistep process in which the dithiol-disulfide oxidoreductase enzyme, DsbA, plays a central role. The structure of DsbA comprises an all helical domain of unknown function and a thioredoxin domain, where active site cysteines shuttle between an oxidized, substrate-bound, reduced form and a DsbB-bound form, where DsbB is a membrane protein that reoxidizes DsbA. Most DsbA enzymes interact with a wide variety of reduced substrates and show little specificity. However, a number of DsbA enzymes have now been identified that have narrow substrate repertoires and appear to interact specifically with a smaller number of substrates. The transient nature of the DsbA-substrate complex has hampered our understanding of the factors that govern the interaction of DsbA enzymes with their substrates. Here we report the crystal structure of a complex between Escherichia coli DsbA and a peptide with a sequence derived from a substrate. The binding site identified in the DsbA-peptide complex was distinct from that observed for DsbB in the DsbA-DsbB complex. The structure revealed details of the DsbA-peptide interaction and suggested a mechanism by which DsbA can simultaneously show broad specificity for substrates yet exhibit specificity for DsbB. This mode of binding was supported by solution nuclear magnetic resonance data as well as functional data, which demonstrated that the substrate specificity of DsbA could be modified via changes at the binding interface identified in the structure of the complex.