HIV-Infected Former Plasma Donors in Rural Central China: From Infection to Survival Outcomes, 1985–2008

BACKGROUND: The HIV epidemic among former plasma donors (FPDs) in rural Central China in the early-mid 1990s is likely the largest known HIV-infected cohort in the world related to commercial plasma donation but has never been fully described. The objectives of this study are to estimate the timing and geographic spread of HIV infection in this cohort and to demonstrate the impact of antiretroviral therapy on survival outcomes. METHODOLOGY/PRINCIPAL FINDINGS: HIV-infected FPDs were identified using the national HIV epidemiology and treatment databases. Locations of subjects were mapped. Dates of infection and survival were estimated using the midpoint date between initial-final plasma donation dates from 1985-2008 among those with plasma donation windows ≤2 years. Among 37,084 FPDs in the two databases, 36,110 were included. 95% were located in focal areas of Henan Province and adjacent areas of surrounding provinces. Midpoint year between initial-final plasma donation dates was 1994 among FPDs with known donation dates. Median survival from infection to AIDS was 11.8 years and, among those not treated, 1.6 years from AIDS to death. Among those on treatment, 71% were still alive after five years. Using Cox proportional hazard modeling, untreated AIDS patients were 4.9 times (95% confidence interval 4.6-5.2) more likely to die than those on treatment. CONCLUSIONS/SIGNIFICANCE: The epidemic of HIV-infected FPD in China was not widespread throughout China but rather was centered in Henan Province and the adjacent areas of surrounding provinces. Even in these areas, infections were concentrated in focal locations. Overall, HIV infections in this cohort peaked in 1994, with median survival of 13.4 years from infection to death among those not treated. Among AIDS patients on treatment, 71% were still alive after five years

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous stimuli. This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Cavα2δ1 expression

Preparation and Characterization of Covalently Binding of Rat Anti-human IgG Monolayer on Thiol-Modified Gold Surface

The 16-mercaptohexadecanoic acid (MHA) film and rat anti-human IgG protein monolayer were fabricated on gold substrates using self-assembled monolayer (SAM) method. The surface properties of the bare gold substrate, the MHA film and the protein monolayer were characterized by contact angle measurements, atomic force microscopy (AFM), grazing incidence X-ray diffraction (GIXRD) method and X-ray photoelectron spectroscopy, respectively. The contact angles of the MHA film and the protein monolayer were 18° and 12°, respectively, all being hydrophilic. AFM images show dissimilar topographic nanostructures between different surfaces, and the thickness of the MHA film and the protein monolayer was estimated to be 1.51 and 5.53 nm, respectively. The GIXRD 2θ degrees of the MHA film and the protein monolayer ranged from 0° to 15°, significantly smaller than that of the bare gold surface, but the MHA film and the protein monolayer displayed very different profiles and distributions of their diffraction peaks. Moreover, the spectra of binding energy measured from these different surfaces could be well fitted with either Au4f, S2p or N1s, respectively. Taken together, these results indicate that MHA film and protein monolayer were successfully formed with homogeneous surfaces, and thus demonstrate that the SAM method is a reliable technique for fabricating protein monolayer

Lack of Association of miR-146a rs2910164 Polymorphism with Gastrointestinal Cancers: Evidence from 10206 Subjects

BACKGROUND: Recent studies on the association between miR-146a rs2910164 polymorphism and risk of gastrointestinal (GI) cancers showed inconclusive results. Accordingly, we conducted a comprehensive literature search and a meta-analysis to clarify the association. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from the following electronic databases: Pubmed, Excerpta Medica Database (Embase), and Chinese Biomedical Literature Database (CBM), with the last report up to February 24, 2012. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of association. Ultimately, a total of 12 studies (4,817 cases and 5,389 controls) were found to be eligible for meta-analysis. We summarized the data on the association between miR-146a rs2910164 polymorphism and risk of GI cancers in the overall population, and performed subgroup analyses by ethnicity, cancer types, and quality of studies. In the overall analysis, there was no evidence of association between miR-146a rs2910164 polymorphism and the risk of GI cancers (G versus C: OR = 1.07, 95%CI 0.98-1.16, P = 0.14; GG+GC versus CC: OR = 1.14, 95%CI 1.00-1.31, P = 0.05; GG versus GC+CC: OR = 1.06, 95%CI 0.91-1.23, P = 0.47; GG versus CC: OR = 1.17, 95%CI 0.95-1.44, P = 0.13; GC versus CC: OR = 1.14, 95%CI 1.00-1.31, P = 0.05). Similar results were found in the subgroup analyses by ethnicity, cancer types, and quality of studies. CONCLUSIONS/SIGNIFICANCE: This meta-analysis demonstrates that miR-146a rs2910164 polymorphism is not associated with GI cancers susceptibility. More well-designed studies based on larger sample sizes and homogeneous cancer patients are needed

Complete Sequencing and Pan-Genomic Analysis of Lactobacillus delbrueckii subsp. bulgaricus Reveal Its Genetic Basis for Industrial Yogurt Production

Lactobacillus delbrueckii subsp. bulgaricus (Lb. bulgaricus) is an important species of Lactic Acid Bacteria (LAB) used for cheese and yogurt fermentation. The genome of Lb. bulgaricus 2038, an industrial strain mainly used for yogurt production, was completely sequenced and compared against the other two ATCC collection strains of the same subspecies. Specific physiological properties of strain 2038, such as lysine biosynthesis, formate production, aspartate-related carbon-skeleton intermediate metabolism, unique EPS synthesis and efficient DNA restriction/modification systems, are all different from those of the collection strains that might benefit the industrial production of yogurt. Other common features shared by Lb. bulgaricus strains, such as efficient protocooperation with Streptococcus thermophilus and lactate production as well as well-equipped stress tolerance mechanisms may account for it being selected originally for yogurt fermentation industry. Multiple lines of evidence suggested that Lb. bulgaricus 2038 was genetically closer to the common ancestor of the subspecies than the other two sequenced collection strains, probably due to a strict industrial maintenance process for strain 2038 that might have halted its genome decay and sustained a gene network suitable for large scale yogurt production

Comparative genomic and transcriptomic analysis revealed genetic characteristics related to solvent formation and xylose utilization in Clostridium acetobutylicum EA 2018

<p>Abstract</p> <p>Background</p> <p><it>Clostridium acetobutylicum</it>, a gram-positive and spore-forming anaerobe, is a major strain for the fermentative production of acetone, butanol and ethanol. But a previously isolated hyper-butanol producing strain <it>C. acetobutylicum </it>EA 2018 does not produce spores and has greater capability of solvent production, especially for butanol, than the type strain <it>C. acetobutylicum </it>ATCC 824.</p> <p>Results</p> <p>Complete genome of <it>C. acetobutylicum </it>EA 2018 was sequenced using Roche 454 pyrosequencing. Genomic comparison with ATCC 824 identified many variations which may contribute to the hyper-butanol producing characteristics in the EA 2018 strain, including a total of 46 deletion sites and 26 insertion sites. In addition, transcriptomic profiling of gene expression in EA 2018 relative to that of ATCC824 revealed expression-level changes of several key genes related to solvent formation. For example, <it>spo0A </it>and <it>adhEII </it>have higher expression level, and most of the acid formation related genes have lower expression level in EA 2018. Interestingly, the results also showed that the variation in CEA_G2622 (CAC2613 in ATCC 824), a putative transcriptional regulator involved in xylose utilization, might accelerate utilization of substrate xylose.</p> <p>Conclusions</p> <p>Comparative analysis of <it>C. acetobutylicum </it>hyper-butanol producing strain EA 2018 and type strain ATCC 824 at both genomic and transcriptomic levels, for the first time, provides molecular-level understanding of non-sporulation, higher solvent production and enhanced xylose utilization in the mutant EA 2018. The information could be valuable for further genetic modification of <it>C. acetobutylicum </it>for more effective butanol production.</p

Genetic Variation of HvCBF Genes and Their Association with Salinity Tolerance in Tibetan Annual Wild Barley

The evaluation of both the genetic variation and the identification of salinity tolerant accessions of Tibetan annual wild barley (hereafter referred to as Tibetan barley) (Hordeum vulgare L. ssp. Spontaneum and H. vulgare L. ssp. agriocrithum) are essential for discovering and exploiting novel alleles involved in salinity tolerance. In this study, we examined tissue dry biomass and the Na+ and K+ contents of 188 Tibetan barley accessions in response to salt stress. We investigated the genetic variation of transcription factors HvCBF1, HvCBF3 and HvCBF4 within these accessions, conducting association analysis between these three genes and the respective genotypic salt tolerance. Salt stress significantly reduced shoot and root dry weight by 27.6% to 73.1% in the Tibetan barley lines. HvCBF1, HvCBF3 and HvCBF4 showed diverse sequence variation in amplicon as evident by the identification of single nucleotide polymorphisms (SNPs) and 3, 8 and 13 haplotypes, respectively. Furthermore, the decay of Linkage disequilibrium (LD) of chromosome 5 was 8.9 cM (r2<0.1). Marker bpb-4891 and haplotype 13 (Ps 610) of the HvCBF4 gene were significantly (P<0.05) and highly significantly (P<0.001) associated with salt tolerance. However, HvCBF1 and HvCBF3 genes were not associated with salinity tolerance. The accessions from haplotype 13 of the HvCBF4 gene showed high salinity tolerance, maintaining significantly lower Na+/K+ ratios and higher dry weight. It is thus proposed that these Tibetan barley accessions could be of value for enhancing salinity tolerance in cultivated barley

The Effect of Central Loops in miRNA:MRE Duplexes on the Efficiency of miRNA-Mediated Gene Regulation

MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of miRNAs have been identified but the target identification of mammalian mRNAs is still a difficult task due to a poor understanding of the interaction between miRNAs and the miRNA recognizing element (MRE). In recent research, the importance of the 5′ end of the miRNA:MRE duplex has been emphasized and the effect of the tail region addressed, but the role of the central loop has largely remained unexplored. Here we examined the effect of the loop region in miRNA:MRE duplexes and found that the location of the central loop is one of the important factors affecting the efficiency of gene regulation mediated by miRNAs. It was further determined that the addition of a loop score combining both location and size as a new criterion for predicting MREs and their cognate miRNAs significantly decreased the false positive rates and increased the specificity of MRE prediction