A20 plays a critical role in the immunoregulatory function of mesenchymal stem cells

Mesenchymal stem cells (MSCs) possess an immunoregulatory capacity and are a therapeutic target for many inflammation‐related diseases. However, the detailed mechanisms of MSC‐mediated immunosuppression remain unclear. In this study, we provide new information to partly explain the molecular mechanisms of immunoregulation by MSCs. Specifically, we found that A20 expression was induced in MSCs by inflammatory cytokines. Knockdown of A20 in MSCs resulted in increased proliferation and reduced adipogenesis, and partly reversed the suppressive effect of MSCs on T cell proliferation in vitro and inhibited tumour growth in vivo. Mechanistic studies indicated that knockdown of A20 in MSCs inhibited activation of the p38 mitogen‐activated protein kinase (MAPK) pathway, which potently promoted the production of tumour necrosis factor (TNF)‐α and inhibited the production of interleukin (IL)‐10. Collectively, these data reveal a crucial role of A20 in regulating the immunomodulatory activities of MSCs by controlling the expression of TNF‐α and IL‐10 in an inflammatory environment. These findings provide novel insights into the pathogenesis of various inflammatory‐associated diseases, and are a new reference for the future development of treatments for such afflictions.     

Differential Expression of microRNAs and their Regulatory Networks in Skin Tissue of Liaoning Cashmere Goat during Hair Follicle Cycles

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that negatively regulate gene expression. Herein, we investigated a selective number of miRNAs for their expression in skin tissue of Liaoning Cashmere goat during hair follicle cycles, and their intracellular regulatory networks were constructed based on bioinformatics analysis. The relative expression of six miRNAs (mir-103-3p, -15b-5p, 17-5p, -200b, -25-3p, and -30c-5p) at anagen phase is significantly higher than that at catagen and/or telogen phases. In comparison to anagen, the relative expression of seven miRNAs (mir-148a-3p, -199a-3p, -199a-5p, -24-3p, -30a-5p, -30e-5p, and -29a-3p) was revealed to be significantly up-regulated at catagen and/or telogen stages. The network analyses of miRNAs indicated those miRNAs investigated might be directly or indirectly involved in several signaling pathways through their target genes. These results provided a foundation for further insight into the roles of these miRNAs in skin tissue of Liaoning Cashmere goat during hair follicle cycles.     

Variations in carbon source–sink relationships in subalpine fir across elevational gradients

• Cold‐adapted trees display acclimation in both carbon source and carbon sink capacity to low‐temperature stress at their upper elevational range limits. Hence a balanced carbon source–sink capacity might be required for their persistence and survival at the elevational tree limits.
• The present study examined the spatial dynamics of carbon source–sink relationship in subalpine fir (Abies fargesii) trees along elevational gradients in the northern slope of the temperate region and in the southern slope of the subtropics in terms of climate in the Qinling Mountain range, north‐central China.
• The results showed that non‐structural carbohydrate (NSC) concentrations in both the source and sink tissues increased with the increase in elevation. The ratio of carbon source–sink displayed a consistent decreasing trend with the increase in elevation and during growing season, showing that it was lowest at a ratio of 2.93 in the northern slope and at a ratio of 2.61 in the southern slope at the upper distribution elevations in the late growing season. Such variations of carbon source–sink ratio might be attributable to the balance between carbon source and sink activities, which changed seasonally across the elevational distribution range.
• We concluded that a ratio of carbon source–sink of at least 2.6 might be essential for subalpine fir trees to persist at their upper range limits. Therefore, a sufficient source–sink ratio and a balanced source–sink relationship might be required for subalpine fir trees to survive and develop at their upper elevational distribution limits.

     

Forest characteristics and population structure of Glyptostrobus pensilis,a globally endangered relict species of southeastern China

The Chinese water pine Glyptostrobus pensilis is the sole surviving species of the genus Glyptostrobus. It is endemic to southern China, central Vietnam, and eastern Laos, and today it is nearly extinct in the wild. Forest community characteristics and population structure of G. pensilis in China have remained un-known up to now. We investigated six swamp forest stands and analyzed their forest community characteristics (i.e. vertical stratification, species composition, and diversity) and population structure, including the frequency distribution of DBH (diameter at breast height) and age-classes as found in Fujian Province, southeastern China. The vertical stratifications of all the forest stands were rather simple. The remaining wild specimens ranged from roughly 15 to some 357 years for an average of ca. 85 years, with only a few individuals less than 20 years old. Compared with the stands and populations of G. pensilis in Vietnam, the taxonomic compositions of the stands in the two regions were different, except for the dominant species-G. pensilis. The Shannon-Wiener index showed the overstory of each stand had much lower diversity (0.26 on average) in Fujian Province than that (1.97 on average) in Vietnam, whereas the diversity indices were about the same (around 2.41) for the understories in the two regions. Furthermore, we discovered 18 G. pensilis seedlings at the study sites in Fujian Province. This discovery demonstrates that G. pensilis regeneration is extremely poor and its populations are declining, although these populations are rela-tively healthier than those in Vietnam.     

亚热带-温带过渡区秦岭落叶阔叶林幼苗组成及数量动态研究

以秦岭落叶阔叶林25 hm²固定样地的木本植物幼苗为研究对象,于2015 - 2019年对幼苗种类、数量、萌发和死亡情况进行调查,并对幼苗的物种组成、数量及动态特征进行分析。结果显示：5年间调查到的幼苗分属24科42属,共69个物种,累计记录 11 408 株;样地中的树种组成和优势树种组成基本不变,但整体物种数有减少趋势;幼苗数量在年际间和不同物种间有较大差异,17个物种幼苗数量较多,大于100株,其总和占幼苗总量的56.28%,产生新增幼苗的物种有53个,累计增加6280株;死亡幼苗6929株,其中4469株为新生幼苗,占新增幼苗总数的74.14%,新苗的死亡数远远大于旧苗死亡数;幼苗新增和死亡的高峰期大致吻合,出现在每年的5 - 7月。整体看来,秦岭大样地的幼苗数量处于平稳波动状态,物种更新较为稳定。     

Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis

Background

Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We evaluated the recently developed microscopic observation drug susceptibility (MODS) assay format for speed and accuracy in diagnosing TBM.

Methodology/Principal Findings

Two hundred and thirty consecutive CSF samples collected from 156 patients clinically suspected of TBM on presentation at a tertiary referal hospital in Vietnam were enrolled into the study over a five month period and tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterial growth Indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. Sixty-one samples were from patients already on TB therapy for >1day and 19 samples were excluded due to untraceable patient records. One hundred and fifty samples from 137 newly presenting patients remained. Forty-two percent (n = 57/137) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Sensitivity by patient against clinical gold standard for ZN smear, MODS MGIT and LJ were 52.6%, 64.9%, 70.2% and 70.2%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 78.7%, respectively for HIV infected patients and 100% and 82.1% for HIV negative patients. The median time to positive was 6 days (interquartile range 5–7), significantly faster than MGIT at 15.5 days (interquartile range 12–24), and LJ at 24 days (interquartile range 18–35 days) (P<0.01).

Conclusions

We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM with high sensitivity, ease of performance and low cost (0.53 USD/sample).     

Discovering robust protein biomarkers for disease from relative expression reversals in 2-D DIGE data

This study assesses the ability of a novel family of machine learning algorithms to identify changes in relative protein expression levels, measured using 2-D DIGE data, which support accurate class prediction. The analysis was done using a training set of 36 total cellular lysates comprised of six normal and three cancer biological replicates (the remaining are technical replicates) and a validation set of four normal and two cancer samples. Protein samples were separated by 2-D DIGE and expression was quantified using DeCyder-2D Differential Analysis Software. The relative expression reversal (RER) classifier correctly classified 9/9 training biological samples (p<0.022) as estimated using a modified version of leave one out cross validation and 6/6 validation samples. The classification rule involved comparison of expression levels for a single pair of protein spots, tropomyosin isoforms and alpha-enolase, both of which have prior association as potential biomarkers in cancer. The data was also analyzed using algorithms similar to those found in the extended data analysis package of DeCyder software. We propose that by accounting for sources of within- and between-gel variation, RER classifiers applied to 2-D DIGE data provide a useful approach for identifying biomarkers that discriminate among protein samples of interest.     

Minimum population size,genetic diversity,and social structure of the Asian elephant in Cat Tien National Park and its adjoining areas,Vietnam, based on molecular genetic analyses

Vietnam’s elephant population that has suffered severe declines during the past three decades is now believed to number 60–80 individuals in the wild. Cat Tien National Park is thought to be one of the key areas for the recovery of Vietnam’s elephants. We carried out a molecular genetic study of elephants in Cat Tien National Park and its adjoining areas with the objectives of estimating minimum population size, assessing genetic diversity, and obtaining insights into social organization. We obtained a minimum population size of 11 elephants based on a combination of unique nuclear microsatellite genotypes and mitochondrial haplotypes. While mitochondrial diversity based on a 600-base pair segment was high in this small sample of individuals, the six microsatellite loci examined showed low diversity and the signature of a recent population bottleneck. Along with nuclear genetic depauperation of Cat Tien’s elephants, we also report disruption of normal social organization, with different matrilines having coalesced into a single social group because of anthropogenic disturbance. The results emphasize the critical condition of this elephant population and the need for urgent conservation measures if this population is to be saved.     

Potent effect of target structure on microRNA function

MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for other experimentally tested miRNA-target interactions in C. elegans and Drosophila melanogaster. These findings indicate a potent effect of target structure on target recognition by miRNAs and establish a structure-based framework for genome-wide identification of animal miRNA targets.