Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.

BackgroundBacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism.ResultsBT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications.ConclusionsStructural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively

Two Pfam protein families characterized by a crystal structure of protein lpg2210 from Legionella pneumophila.

BackgroundEvery genome contains a large number of uncharacterized proteins that may encode entirely novel biological systems. Many of these uncharacterized proteins fall into related sequence families. By applying sequence and structural analysis we hope to provide insight into novel biology.ResultsWe analyze a previously uncharacterized Pfam protein family called DUF4424 [Pfam:PF14415]. The recently solved three-dimensional structure of the protein lpg2210 from Legionella pneumophila provides the first structural information pertaining to this family. This protein additionally includes the first representative structure of another Pfam family called the YARHG domain [Pfam:PF13308]. The Pfam family DUF4424 adopts a 19-stranded beta-sandwich fold that shows similarity to the N-terminal domain of leukotriene A-4 hydrolase. The YARHG domain forms an all-helical domain at the C-terminus. Structure analysis allows us to recognize distant similarities between the DUF4424 domain and individual domains of M1 aminopeptidases and tricorn proteases, which form massive proteasome-like capsids in both archaea and bacteria.ConclusionsBased on our analyses we hypothesize that the DUF4424 domain may have a role in forming large, multi-component enzyme complexes. We suggest that the YARGH domain may play a role in binding a moiety in proximity with peptidoglycan, such as a hydrophobic outer membrane lipid or lipopolysaccharide

Two decades of research on migrant health in China: A systematic review. Lessons for future inquiry

This paper examines the adequacy, quality and relevance of existing evidence on migrant health in China as a guide to future research and policy. It uses a systematic review to identify publications on migrant health issues in China between 1985 and 2010 from selected databases. It also assesses the technical focus and methodologies for the 1,216 research articles retrieved. The volume of research on migrant health issues has grown nearly 55-fold between 1985-2000 and 2006-2010, with the publication of nearly 194 studies annually during the latter period. Almost two-thirds of the studies (68 per cent) sampled only migrants, with no comparison group either from destination urban areas or sending rural areas. Less than one-tenth of the studies evaluated a specific intervention (9 per cent); among those, most sampled only migrants and used a before-after design. The research tended to focus on communicable diseases (43 per cent), with HIV/AIDS accounting for 26 per cent. Research on health systems and non-communicable diseases represented 9 per cent and 13 per cent of the studies, respectively. More than half of the studies (54 per cent) were carried out in cities in four provinces, with few investigating family members left behind in rural areas. Despite a substantial increase in volume, research on migrant health in China has provided limited information to inform current policies and programmes. Most studies are descriptive and disproportionately focused on a handful of communicable diseases, neglecting some of the pressing policy-relevant issues in China on service access. Few studies have comparison populations. Increasing the rigour and relevance of future research will require better sampling frames with comparison populations; a focus on neglected research areas, including access to services; and partnerships with government and other agencies to evaluate specific interventions

Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway.

Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regulated by mTORC1, a sensor of nutrients and growth factors, which is highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes are recapitulated in intestinal stem cell-specific Tsc1 knockout mice. Mechanistically, mTORC1 activation increases protein synthesis of MKK6 and augments activation of the p38 MAPK-p53 pathway, leading to decreases in the number and activity of intestinal stem cells as well as villus size and density. Targeting p38 MAPK or p53 prevents or rescues ISC and villus aging and nutrient absorption defects. These findings reveal that mTORC1 drives aging by augmenting a prominent stress response pathway in gut stem cells and identify p38 MAPK as an anti-aging target downstream of mTORC1

Modeling and Experimental Verification of an Electromagnetic and Piezoelectric Hybrid Energy Harvester

This paper describes mathematical models of an electromagnetic and piezoelectric hybrid energy harvesting system and provides an analysis of the relationship between the resonance frequency and the configuration parameters of the system. An electromagnetic and piezoelectric energy harvesting device was designed and the experimental results showed good agreement with the analytical results. The maximum load power of the hybrid energy harvesting system achieved 4.25 mW at a resonant frequency of 18 Hz when the acceleration was 0.7 g, which is an increase of 15% compared with the 3.62 mW achieved by a single electromagnetic technique

Changes on content, structure and surface distribution of lignin in jute fibers after laccase treatment

Effect of laccase treatment on the content, structure, and surface distribution of lignin in jute fibers were fundamentally investigated. Four percent lignin was removed from jute fibers via the laccase treatment. The residual lignin in the laccase-treated jute fibers showed increased molecular weights, which indicated polymerization between lignins on jute fibers. Meanwhile, the phenolic hydroxyl content in lignin decreased during the laccase oxidation accompanied by demethylation of methoxyl groups and generation of carbonyl groups. Due to the degradation and subsequent polymerization of lignin by laccase, the bulgy lignins on jute fiber surfaces were redistributed, which made the surface neat and glossy.This work was financially supported by the National Natural Science Foundations of China (51603087, 51673087), Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R26), Fundamental Research Funds for the Central Universities (JUSRP51717A), Key R&D Program of Jiangsu Province (BE2016208), Portuguese Foundation for Science and Technology (UID/BIO/04469/2013 unit), and COMPETE 2020 (POCI-01-0145-FEDER006684).info:eu-repo/semantics/publishedVersio

Weight loss reduces basal-like breast cancer through kinome reprogramming

Additional file 1. Tumor burden and growth were not affected by diet. a. Tumor burden was quantified at sacrifice. b. Tumor volume was measured by calipers at detection and sacrifice. (N = 28 10 %; N = 31 60 %; N = 29, 60–10 %)

In situ characterization of mesoporous Co/CeO2 catalysts for the high-temperature water-gas shift

Mesoporous Co/CeO2 catalysts were found to exhibit significant activity for the high-temperature water-gas shift (WGS) reaction with cobalt loadings as low as 1 wt %. The catalysts feature a uniform dispersion of cobalt within the CeO2 fluorite type lattice with no evidence of discrete cobalt phase segregation. In situ XANES and ambient pressure XPS experiments were used to elucidate the active state of the catalysts as partially reduced cerium oxide doped with oxidized cobalt atoms. In situ XRD and DRIFTS experiments suggest facile cerium reduction and oxygen vacancy formation, particularly with lower cobalt loadings. In situ DRIFTS analysis also revealed the presence of surface carbonate and bidentate formate species under reaction conditions, which may be associated with additional mechanistic pathways for the WGS reaction. Deactivation behavior was observed with higher cobalt loadings. XANES data suggest the formation of small metallic cobalt clusters at temperatures above 400 °C may be responsible. Notably, this deactivation was not observed for the 1% cobalt loaded catalyst, which exhibited the highest activity per unit of cobalt.Peer ReviewedPostprint (author's final draft