A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency

Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe and characterized by early and progressive chronic kidney disease (CKD). No treatment is currently available for FLD, but novel therapeutics are under development. Furthermore, although biomarkers of LCAT deficiency have been identified, their suitability to monitor disease progression and therapeutic efficacy is unclear, as little data exist on the rate of progression of renal disease. Here, we systematically review observational studies of FLD, FED, and heterozygous subjects, which summarize available evidence on the natural history and biomarkers of LCAT deficiency, in order to guide the development of novel therapeutics. We identified 146 FLD and 53 FED patients from 219 publications, showing that both syndromes are characterized by early corneal opacity and markedly reduced HDL-C levels. Proteinuria/hematuria were the first signs of renal impairment in FLD, followed by rapid decline of renal function. Furthermore, LCAT activity toward endogenous substrates and the percentage of circulating esterified cholesterol (EC%) were the best discriminators between these two syndromes. In FLD, higher levels of total, non-HDL, and unesterified cholesterol were associated with severe CKD. We reveal a nonlinear association between LCAT activity and EC% levels, in which subnormal levels of LCAT activity were associated with normal EC%. This review provides the first step toward the identification of disease biomarkers to be used in clinical trials and suggests that restoring LCAT activity to subnormal levels may be sufficient to prevent renal disease progression.     

Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing,China

Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5' UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45×10^-3 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.     

模拟边坡条件下常见护坡植物苗期根系构型特征

植物根系对提高边坡稳定性具有重要作用。采用喷播的方式在侵蚀槽中制备模拟石质边坡,植物生长6个月后采用全根挖掘和Win-RHIZO根系分析仪扫描相结合的方法,研究了模拟边坡条件下11种常见护坡植物苗期的根系构型特征。结果表明：紫花苜蓿根系生物量最大,柠条根系生物量最小,二者主根发达,仅分布在下坡方向。沙打旺、胡枝子、紫穗槐和欧李根系生物量、总根数、总基根数、总根长、总根表面积、总根体积均较大,在上坡方向和下坡方向分布均匀,拓扑指数介于0.53—0.61之间,为叉状分枝结构,根系固土护坡能力较强,可作为边坡生态修复工程的优选植物。根系生物量与根系表面积、根体积呈现显著的线性正相关关系(R²分别为0.68和0.80),拓扑指数与根系长度、根系表面积、总根数、总基根数呈现显著的指数负相关关系(R²分别为0.82、0.68、0.87、0.86),可为植物根系构型研究提供科学依据及理论支撑。     

Altered Fecal Microbiota Composition Associated with Food Allergy in Infants

Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P = 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R = 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.     

Elevational diversity and distribution of ammonia-oxidizing archaea community in meadow soils on the Tibetan Plateau

Unraveling elevational diversity patterns of plants and animals has long been attracting scientific interests. However, whether soil microorganisms exhibit similar elevational patterns remains largely less explored, especially for functional microbial communities, such as ammonia oxidizers. Here, we investigated the diversity and distribution pattern of ammonia-oxidizing archaea (AOA) in meadow soils along an elevation gradient from 4400 m to the grassline at 5100 m on the Tibetan Plateau using terminal restriction fragment length polymorphism (T-RFLP) and sequencing methods by targeting amoA gene. Increasing elevations led to lower soil temperature and pH, but higher nutrients and water content. The results showed that AOA diversity and evenness monotonically increased with elevation, while richness was relatively stable. The increase of diversity and evenness was attributed to the growth inhibition of warm-adapted AOA phylotypes by lower temperature and the growth facilitation of cold-adapted AOA phylotypes by richer nutrients at higher elevations. Low temperature thus played an important role in the AOA growth and niche separation. The AOA community variation was explained by the combined effect of all soil properties (32.6%), and 8.1% of the total variation was individually explained by soil pH. The total AOA abundance decreased, whereas soil potential nitrification rate (PNR) increased with increasing elevations. Soil PNR positively correlated with the abundance of cold-adapted AOA phylotypes. Our findings suggest that low temperature plays an important role in AOA elevational diversity pattern and niche separation, rising the negative effects of warming on AOA diversity and soil nitrification process in the Tibetan region.     

Progress in the gut microbiota in exploring shrimp disease pathogenesis and incidence

Applied Microbiology and Biotechnology - It is now recognized that gut microbiota contributes indispensable roles in safeguarding host health. Shrimp is being threatened by newly emerging diseases...     

Microbial Communities and Functional Genes Associated with Soil Arsenic Contamination and the Rhizosphere of the Arsenic-Hyperaccumulating Plant Pteris vittata L.

To understand how microbial communities and functional genes respond to arsenic contamination in the rhizosphere of Pteris vittata, five soil samples with different arsenic contamination levels were collected from the rhizosphere of P. vittata and nonrhizosphere areas and investigated by Biolog, geochemical, and functional gene microarray (GeoChip 3.0) analyses. Biolog analysis revealed that the uncontaminated soil harbored the greatest diversity of sole-carbon utilization abilities and that arsenic contamination decreased the metabolic diversity, while rhizosphere soils had higher metabolic diversities than did the nonrhizosphere soils. GeoChip 3.0 analysis showed low proportions of overlapping genes across the five soil samples (16.52% to 45.75%). The uncontaminated soil had a higher heterogeneity and more unique genes (48.09%) than did the arsenic-contaminated soils. Arsenic resistance, sulfur reduction, phosphorus utilization, and denitrification genes were remarkably distinct between P. vittata rhizosphere and nonrhizosphere soils, which provides evidence for a strong linkage among the level of arsenic contamination, the rhizosphere, and the functional gene distribution. Canonical correspondence analysis (CCA) revealed that arsenic is the main driver in reducing the soil functional gene diversity; however, organic matter and phosphorus also have significant effects on the soil microbial community structure. The results implied that rhizobacteria play an important role during soil arsenic uptake and hyperaccumulation processes of P. vittata.Arsenic (As) is an abundant and widespread trace metalloid element present in virtually all environmental media and is well known to be carcinogenic even at low levels (24). Arsenic contaminations in soil and groundwater have been reported in many parts of the world (2, 29, 34). Recently, in parts of Asia, including China, chronic drinking of arsenic-contaminated groundwater has caused endemic arsenicosis, which has become a major threat to public health (36). Soil arsenic contamination also affects the physiology, growth, and grain quality of crops. For example, high arsenic concentrations were found in rice seeds from Chenzhou, Hunan province, which exceeded the maximal permissible limit of 0.5 mg/kg (dry weight) (21). Hence, remediation of arsenic-contaminated soil and water is one of the major challenges in environmental science and public health. Low-cost, efficient, and environmentally friendly remediation technologies to remove arsenic from contaminated soil and water are urgently needed.Phytoremediation, the use of plants to restore contaminated soil, has attracted great attention recently. A pivotal step toward the phytoremediation of arsenic-contaminated soils is the discovery of the arsenic hyperaccumulator Pteris vittata L. (Chinese brake fern), which possesses high arsenic tolerance and produces a large biomass. This plant species holds great promise for the phytoremediation of arsenic-contaminated soils. It was shown previously that the leaflets of P. vittata were able to accumulate about 100-fold of arsenic from soils (22). Plant arsenic uptake depends mainly on the arsenic source and bioavailability (25). P. vittata remediates arsenic contamination mainly by taking up arsenate [As(V)] via phosphate transport systems, whereas arsenite [As(III)] is very slowly taken up by P. vittata, at 1/10 of the rate of that for arsenate in the absence of phosphate (41). However, the uptake mechanisms still remain largely unknown.Microorganisms play a crucial role in arsenic geochemical cycling through microbial transformation processes, including reduction, oxidation, and methylation (2, 11, 31, 33, 40). Although the impacts of microbial metabolisms were previously reported to be associated with arsenic cycling of soil and water (7, 29), little is known about how rhizobacterial communities of P. vittata respond to arsenic. Recently, we found that inoculating arsenic resistance bacteria increased the arsenic accumulation efficiency of P. vittata by 13 to 110% (46). Therefore, rhizobacteria may play an important role during arsenic uptake and accumulation processes by P. vittata. Thus, it is important to elucidate the microbially diverse populations and functional genes associated with arsenic mobility and transport in the P. vittata rhizosphere. However, to fully understand the ecology of such complex rhizosphere-contaminated soils, it is necessary to analyze different microbial populations simultaneously.Our hypothesis is that the arsenic-hyperaccumulating ability of P. vittata is due to the interactions among plants, rhizobacteria, and arsenic. A study of microbial communities present in the plant rhizosphere is important to illustrate the mechanisms of arsenic hyperaccumulation in P. vittata. Thus, the objectives of this research were to understand how microbial metabolic diversities, communities, and functional genes/relative abundances were affected by soil arsenic contamination and the P. vittata rhizosphere environment. To determine the soil microbial metabolic diversity, the Biolog system (Biolog, Carlsbad, CA) was used to analyze the sole-carbon-source-utilizing capabilities of the soil microbial communities. For functional gene analysis, a high-density, sensitive, oligonucleotide-based microarray (GeoChip 3.0) was used. GeoChip-based technologies have revealed the structure, metabolic activity, and dynamics of microbial communities from complex environments, such as soil, sediments, and groundwater (10, 38, 39, 45, 48). Our results provide evidence that changes of microbial community structure, functional gene distribution, and microbial metabolic diversity are associated with the soil arsenic level and the rhizosphere effect of P. vittata and suggest that plant phytoremediation is an interactive process among plants, microorganisms, and soil contaminants.     

Protein structure prediction enhanced with evolutionary diversity: SPEED

For naturally occurring proteins, similar sequence implies similar structure. Consequently, multiple sequence alignments (MSAs) often are used in template‐based modeling of protein structure and have been incorporated into fragment‐based assembly methods. Our previous homology‐free structure prediction study introduced an algorithm that mimics the folding pathway by coupling the formation of secondary and tertiary structure. Moves in the Monte Carlo procedure involve only a change in a single pair of ?,ψ backbone dihedral angles that are obtained from a Protein Data Bank‐based distribution appropriate for each amino acid, conditional on the type and conformation of the flanking residues. We improve this method by using MSAs to enrich the sampling distribution, but in a manner that does not require structural knowledge of any protein sequence (i.e., not homologous fragment insertion). In combination with other tools, including clustering and refinement, the accuracies of the predicted secondary and tertiary structures are substantially improved and a global and position‐resolved measure of confidence is introduced for the accuracy of the predictions. Performance of the method in the Critical Assessment of Structure Prediction (CASP8) is discussed.