Filamentous vibriophage fs2 encoding the rstC gene integrates into the same chromosomal region as cholera toxin X

The genome of the filamentous phage of Vibrio cholerae fs2 was found to contain rst C and rst B1 (truncated) genes downstream of ORF500. att -fs2-dir and att- fs2-rev sequences homologous to that of att -CTXφ were found between orf 500 and rst C of the fs2 genome. This prompted us to search for the integration site of fs2 in the genomes of V. cholerae O1 and O139. The genome of fs2 was found to integrate downstream of att RS of the CTXφ phage, which integrated into chromosome I of V. cholerae O1 and O139. When infected with fs2, a fimbriate strain of V. cholerae O1 appeared to reduce fimbrial production in an adult rabbit ileal loop assay.     

Human cardiac fibroblasts produce pro-inflammatory cytokines upon TLRs and RLRs stimulation

Molecular and Cellular Biochemistry - Heart inflammation is one of the major causes of heart damage that leads to dilated cardiomyopathy and often progresses to end-stage heart failure. In the...     

Dynamics and stability of polymorphic human telomeric G-quadruplex under tension

As critical DNA structures capping the human chromosome ends, the stability and structural polymorphism of human telomeric G-quadruplex (G4) have drawn increasing attention in recent years. This work characterizes the equilibrium transitions of single-molecule telomeric G4 at physiological K⁺ concentration. We report three folded states of telomeric G4 with markedly different lifetime and mechanical stability. Our results show that the kinetically favored folding pathway is through a short-lived intermediate state to a longer-lived state. By examining the force dependence of transition rates, the force-dependent transition free energy landscape for this pathway is determined. In addition, an ultra-long-lived form of telomeric G4 structure with a much stronger mechanical stability is identified.     

Findings from Integrated Behavioral and Biologic Survey among Males Who Inject Drugs (MWID) — Vietnam, 2009–2010: Evidence of the Need for an Integrated Response to HIV,Hepatitis B Virus,and Hepatitis C Virus

IntroductionGiven the overlapping modes of transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV), understanding the burden and relationship of these infections is critical for an effective response. Representative data on these infections among males who inject drugs (MWID), the key high-risk population for HIV in Vietnam, are currently lacking.MethodsData and stored specimens from Vietnam’s 2009-2010 Integrated Biologic and Behavioral Survey, a cross-sectional study among high-risk populations, were used for this analysis. Plasma samples were tested for HIV, HBV, and HCV using commercial assays. A questionnaire was administered to provide demographic, behavior, and service-uptake information. Provincial-level analyses were conducted to profile MWID enrollees and to provide estimates on the prevalence of HIV, HBV, and HCV infection.ResultsAmong 3010 MWID sampled across 10 provinces, the median (range) HIV prevalence was 28.1% (1.0%-55.5%). Median prevalence for current HBV infection (HBsAg+) was 14.1% (11.7%-28.0%), for previous exposure to HBV (total anti-HBc+) was 71.4% (49.9%-83.1%), and for current or past HCV infection (HCV Ag/Ab+) was 53.8% (10.9%-80.8%). In adjusted analysis, HBsAg+ (aOR: 2.09, 1.01-4.34) and HCV Ag/Ab+ (aOR: 19.58, 13.07-29.33) status were significantly associated with HIV infection; the association with total anti-HBc+ approached significance (aOR: 1.29, 0.99-1.68).ConclusionThe prevalence and association between HIV, HBV, and HCV are high among MWID in Vietnam. These findings indicate the need for integrated policies and practice that for the surveillance, prevention, screening, and treatment of both HIV and viral hepatitis among MWID in Vietnam.     

Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a Rabbit Model of Atherothrombosis

IntroductionThe detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture.ConclusionsOur targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout.     

A late embryogenesis abundant protein HVA1 regulated by an inducible promoter enhances root growth and abiotic stress tolerance in rice without yield penalty

Regulation of root architecture is essential for maintaining plant growth under adverse environment. A synthetic abscisic acid (ABA)/stress‐inducible promoter was designed to control the expression of a late embryogenesis abundant protein (HVA1) in transgenic rice. The background of HVA1 is low but highly inducible by ABA, salt, dehydration and cold. HVA1 was highly accumulated in root apical meristem (RAM) and lateral root primordia (LRP) after ABA/stress treatments, leading to enhanced root system expansion. Water‐use efficiency (WUE) and biomass also increased in transgenic rice, likely due to the maintenance of normal cell functions and metabolic activities conferred by HVA1 which is capable of stabilizing proteins, under osmotic stress. HVA1 promotes lateral root (LR) initiation, elongation and emergence and primary root (PR) elongation via an auxin‐dependent process, particularly by intensifying asymmetrical accumulation of auxin in LRP founder cells and RAM, even under ABA/stress‐suppressive conditions. We demonstrate a successful application of an inducible promoter in regulating the spatial and temporal expression of HVA1 for improving root architecture and multiple stress tolerance without yield penalty.     

USP18 lack in microglia causes destructive interferonopathy of the mouse brain

Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called “microgliopathies”. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. Here, we identified the ubiquitin‐specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence. We further found that microglial Usp18 negatively regulates the activation of Stat1 and concomitant induction of interferon‐induced genes, thereby terminating IFN signaling. The Usp18‐mediated control was independent from its catalytic activity but instead required the interaction with Ifnar2. Additionally, the absence of Ifnar1 restored microglial activation, indicating a tonic IFN signal which needs to be negatively controlled by Usp18 under non‐diseased conditions. These results identify Usp18 as a critical negative regulator of microglia activation and demonstrate a protective role of Usp18 for microglia function by regulating the Ifnar pathway. The findings establish Usp18 as a new molecule preventing destructive microgliopathy.     

Recombinase and translesion DNA polymerase decrease the speed of replication fork progression during the DNA damage response in Escherichia coli cells

The SOS response is a DNA damage response pathway that serves as a general safeguard of genome integrity in bacteria. Extensive studies of the SOS response in Escherichia coli have contributed to establishing the key concepts of cellular responses to DNA damage. However, how the SOS response impacts on the dynamics of DNA replication fork movement remains unknown. We found that inducing the SOS response decreases the mean speed of individual replication forks by 30–50% in E. coli cells, leading to a 20–30% reduction in overall DNA synthesis. dinB and recA belong to a group of genes that are upregulated during the SOS response, and encode the highly conserved proteins DinB (also known as DNA polymerase IV) and RecA, which, respectively, specializes in translesion DNA synthesis and functions as the central recombination protein. Both genes were independently responsible for the SOS-dependent slowdown of replication fork progression. Furthermore, fork speed was reduced when each gene was ectopically expressed in SOS-uninduced cells to the levels at which they are expressed in SOS-induced cells. These results clearly indicate that the increased expression of dinB and recA performs a novel role in restraining the progression of an unperturbed replication fork during the SOS response.     

Suboptimal breastfeeding practices are associated with infant illness in Vietnam

Background

Despite evidence supporting the importance of breastfeeding to child health, breastfeeding practices remain suboptimal in Vietnam. There is currently little evidence on the importance of breastfeeding in the prevention of morbidity during infancy in Vietnam. In order to provide country specific data for policy makers to support breastfeeding friendly policies and programs, analysis was undertaken on a cross-sectional dataset to investigate the association between breastfeeding practices and prevalence of diarrhea and acute respiratory infection (ARI) among infants aged 0–5 months.

Methods

Data on socio-demographic characteristics, infant feeding practices and prevalence of diarrhea and ARI were obtained from 6,068 mother-child dyads in 11 provinces of Vietnam in 2011. Multivariate logistic regression was used to examine the associations between breastfeeding practices and child illnesses.

Results

On average, the prevalence of diarrhea and ARI among infants 0–5 months was 5.3% and 24.5%, respectively. Though half of all infants were breastfed within one hour of birth, 73.3% were given prelacteal foods in the first three days after birth. Only 20.2% of children 0–5 months old were exclusively breastfed, while 32.4% were predominantly breastfed and 47.4% partially breastfed. After adjusting for confounders, early initiation of breastfeeding was associated with lower prevalence of diarrhea [adjusted odds ratio (AOR)?=?0.74 (95% CI 0.58, 0.93)], while prelacteal feeding was associated with higher prevalence [AOR?=?1.53 (95% CI 1.15, 2.03)]. Compared to infants who were exclusively breastfed, infants who were predominantly [AOR?=?1.52 (95% CI 1.05, 2.21)] or partially breastfed [AOR?=?1.55 (95% CI 1.07, 2.24)] were more likely to have diarrhea. Prelacteal feeding [AOR?=?1.16 (95% CI 1.01, 1.33)] and partial breastfeeding [AOR relative to exclusive breastfeeding?=?1.24 (95% CI 1.03, 1.48)] were associated with higher prevalence of ARI. While the protective effects of exclusive breastfeeding against diarrhea declined with child age, this effect for ARI appears to have remained constant.

Conclusions

Early initiation and exclusive breastfeeding protects against diarrhea and ARI. Results confirm that interventions to improve early and exclusive breastfeeding would contribute to improving child health and nutrition in Vietnam.