Molecular Epidemiology and Clinical Characteristics of Drug-Resistant Mycobacterium tuberculosis in a Tuberculosis Referral Hospital in China

Background

Despite the large number of drug-resistant tuberculosis (TB) cases in China, few studies have comprehensively analyzed the drug resistance-associated gene mutations and genotypes in relation to the clinical characteristics of M. tuberculosis (Mtb) isolates.

Methodology/Principal Findings

We thus analyzed the phenotypic and genotypic drug resistance profiles of 115 Mtb clinical isolates recovered from a tuberculosis referral hospital in Beijing, China. We also performed genotyping by 28 loci MIRU-VNTR analysis. Socio-demographic and clinical data were retrieved from medical records and analyzed. In total, 78 types of mutations (including 42 previously reported and 36 newly identified ones) were identified in 115 Mtb clinical isolates. There was significant correlation between phenotypic and genotypic drug resistance rates for first-line anti-TB drugs (P<0.001). Genotyping revealed 101 MIRU-VNTR types, with 20 isolates (17.4%) being clustered and 95 isolates (82.6%) having unique genotypes. Higher proportion of re-treatment cases was observed among patients with clustered isolates than those with unique MIRU-VNTR genotypes (75.0% vs. 41.1%). Moreover, clinical epidemiological links were identified among patients infected by Mtb strains belonging to the same clusters, suggesting a potential of transmission among patients.

Conclusions/Significance

Our study provided information on novel potential drug resistance-associated mutations in Mtb. In addition, the genotyping data from our study suggested that enforcement of the implementation of genotyping in diagnostic routines would provide important information for better monitor and control of TB transmission.     

Naringin Treatment Improves Functional Recovery by Increasing BDNF and VEGF Expression, Inhibiting Neuronal Apoptosis After Spinal Cord Injury

The aim of this study was to determine the therapeutic efficacy of starting naringin treatment 1 day after spinal cord injury (SCI) in rat and to investigate the underlying mechanism. SCI was induced using the modified weight-drop method in Sprague-Dawley rats. The SCI animals were randomly divided into three groups: vehicle-treated group; 20 mg/kg naringin-treated group; 40 mg/kg naringin-treated group, and additionally with sham group (laminectomy only). Locomotors functional recovery was assessed during the 6 weeks post operation period by performing open-field locomotors tests and inclined-plane tests. At the end of the study, the segments of spinal cord encompassing the injury site were removed for histopathological analysis. Immunohistochemistry was performed to observe the expression of the brain-derived neurotrophic factor (BDNF). The expression of vascular endothelial growth factor (VEGF), B-cell CLL/lymphoma-2 (Bcl-2), BCL-2-associated X protein (Bax) and caspase-3 were detected by Western blot analysis. The apoptotic neural cells were assessed using the TUNEL method. The results showed that the naringin-treated animals had significantly better locomotor function recovery, less myelin loss, and higher expression of BDNF and VEGF. In addition, naringin treatment significantly increased in Bcl-2:Bax ratio, reduced the enzyme activity of caspase-3 and decreased the number of apoptotic cells after SCI. These findings suggest that naringin treatment starting 1 day after SCI can significantly improve locomotor recovery, and this neuroprotective effect may be related to the upregulation of BDNF and VEGF and the inhibition of neural apoptosis. Therefore, naringin may be useful as a promising therapeutic agent for SCI.     

The spatial and temporal dynamics of rabies in China

Background and Objectives

Recent years have seen a rapid increase in the number of rabies cases in China and an expansion in the geographic distribution of the virus. In spite of the seriousness of the outbreak and increasing number of fatalities, little is known about the phylogeography of the disease in China. In this study, we report an analysis of a set of Nucleocapsid sequences consisting of samples collected through the trial Chinese National Surveillance System as well as publicly available sequences. This sequence set represents the most comprehensive dataset from China to date, comprising 210 sequences (including 57 new samples) from 15 provinces and covering all epidemic regions. Using this dataset we investigated genetic diversity, patterns of distribution, and evolutionary history.

Results

Our analysis indicates that the rabies virus in China is primarily defined by two clades that exhibit distinct population subdivision and translocation patterns and that contributed to the epidemic in different ways. The younger clade originated around 1992 and has properties that closely match the observed spread of the recent epidemic. The older clade originated around 1960 and has a dispersion pattern that suggests it represents a strain associated with a previous outbreak that remained at low levels throughout the country and reemerged in the current epidemic.

Conclusions

Our findings provide new insight into factors associated with the recent epidemic and are relevant to determining an effective policy for controlling the virus.     

The oldest known occurrence of the Foliomena fauna in the uppermost Darriwilian (Middle Ordovician) of South China

The oldest Foliomena fauna was, until now, known from the middle–upper Miaopo Formation (Nemagraptus gracilis Biozone, lower Sandbian, basal Upper Ordovician) of South China. In this study, the oldest record of the fauna is set back to the latest Darriwilian (upper Hustedograptus teretiusculus Biozone), represented by Foliomena jielingensis and some typical constituents of the Foliomena fauna from the basal Miaopo Formation at Jieling, northern Yichang, western Hubei Province, central China. The Miaopo Formation is characterized by its organic‐rich dark‐grey shale facies, unique in its localized distribution on the Yangtze Platform, and distinguished by its rich and diverse benthic and graptolitic faunas. This suggests an origin of the Foliomena fauna in periodically oxygen‐starved local depressions on the Yangtze Platform during the Middle–Late Ordovician transition.     

Maximum tree: a consistent estimator of the species tree

We propose a model based approach to use multiple gene trees to estimate the species tree. The coalescent process requires that gene divergences occur earlier than species divergences when there is any polymorphism in the ancestral species. Under this scenario, speciation times are restricted to be smaller than the corresponding gene split times. The maximum tree (MT) is the tree with the largest possible speciation times in the space of species trees restricted by available gene trees. If all populations have the same population size, the MT is the maximum likelihood estimate of the species tree. It can be shown the MT is a consistent estimator of the species tree even when the MT is built upon the estimates of the true gene trees if the gene tree estimates are statistically consistent. The MT converges in probability to the true species tree at an exponential rate.     

Essential role for the Pak4 protein kinase in extraembryonic tissue development and vessel formation

Pak4 is a member of the group B family of Pak serine/threonine kinases, originally identified as an effector protein for the Rho GTPase Cdc42. Pak4 knockout mice are embryonic lethal and do not survive past embryonic day 11.5. Previous work on Pak4 knockout mice has focused on studying the phenotype of the embryo. Abnormalities in the extraembryonic tissue, however, are common causes of early embryonic death in knockout mice. Extraembryonic tissue associated with the Pak4-null embryos was therefore examined. Abnormalities in both yolk sacs and placentas resulted when Pak4 was deleted. These included a lack of vasculature throughout the extraembryonic tissue, as well as an abnormally formed labyrinthine layer of the placenta. Interestingly, epiblast-specific deletion of Pak4 using a conditional knockout system, did not rescue the embryonic lethality. In fact, it did not even rescue the extraembryonic tissue defects. Our results suggest that the extraembryonic tissue abnormalities are secondary to defects that occur in response to epiblast abnormalities. More detailed analysis suggests that abnormalities in vasculature throughout the extraembryonic tissue and the epiblast may contribute to the death of the Pak4-null embryos.     

Big‐sized trees overrule remaining trees' attributes and species richness as determinants of aboveground biomass in tropical forests

Large‐diameter, tall‐stature, and big‐crown trees are the main stand structures of forests, generally contributing a large fraction of aboveground biomass, and hence play an important role in climate change mitigation strategies. Here, we hypothesized that the effects of large‐diameter, tall‐stature, and big‐crown trees overrule the effects of species richness and remaining trees attributes on aboveground biomass in tropical forests (i.e., we term the “big‐sized trees hypothesis”). Specifically, we assessed the importance of: (a) the “top 1% big‐sized trees effect” relative to species richness; (b) the “99% remaining trees effect” relative to species richness; and (c) the “top 1% big‐sized trees effect” relative to the “99% remaining trees effect” and species richness on aboveground biomass. Using environmental factor and forest inventory datasets from 712 tropical forest plots in Hainan Island of southern China, we tested several structural equation models for disentangling the relative effects of big‐sized trees, remaining trees attributes, and species richness on aboveground biomass, while considering for the full (indirect effects only) and partial (direct and indirect effects) mediation effects of climatic and soil conditions, as well as interactions between species richness and trees attributes. We found that top 1% big‐sized trees attributes strongly increased aboveground biomass (i.e., explained 55%–70% of the accounted variation) compared to species richness (2%–18%) and 99% remaining trees attributes (6%–10%). In addition, species richness increased aboveground biomass indirectly via increasing big‐sized trees but via decreasing remaining trees. Hence, we show that the “big‐sized trees effect” overrides the effects of remaining trees attributes and species richness on aboveground biomass in tropical forests. This study also indicates that big‐sized trees may be more susceptible to atmospheric drought. We argue that the effects of big‐sized trees on species richness and aboveground biomass should be tested for better understanding of the ecological mechanisms underlying forest functioning.