Engineering the Campylobacter jejuni N-glycan to create an effective chicken vaccine.

Campylobacter jejuni is a predominant cause of human gastroenteritis worldwide. Source-attribution studies indicate that chickens are the main reservoir for infection, thus elimination of C. jejuni from poultry would significantly reduce the burden of human disease.

Effects of structured vocational services in ex-offender veterans with mental illness: 6-month follow-up.

With more than 200,000 veterans incarcerated, a significant need exists for the development of technologies that help veterans with felony histories return to employment. This study evaluated the effect of three methods of vocational assistance on competitive employment over a 6 mo follow-up period: (1) basic vocational services, (2) self-study using a vocational manual designed for formerly incarcerated veterans, and (3) a group led by vocational staff using the vocational manual. We evaluated 111 veterans for time to obtain and total time of competitive employment.

Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City.

Background: Transmitted drug resistance (TDR) is critical to managing HIV-1-infected individuals and being a public health concern. We report on TDR prevalence and include analyses of phylogenetic clustering of HIV-1 in a predominantly men who have sex with men cohort diagnosed during acute/recent HIV-1 infection in New York City.

Methods: Genotypic resistance testing was conducted on plasma samples of 600 individuals with acute/recent HIV-1 infection (1995-2010).

Regulation of pri-miRNA Processing Through Smads.

microRNAs (miRNAs) are small (∼22 nucleotides (nt)), noncoding RNAs that play a critical role in diverse biological functions by modulating mRNA stability and translational control. Numerous miRNA profiling studies have indicated that the levels of miRNAs are tightly controlled during developmental stages and various pathophysiological and physiological conditions. Following transcription, the long primary miRNA transcript undergoes a series of coordinated maturation steps to generate the mature miRNA.

Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha.

The signal transducers of the transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP), the Smads, promote the expression of a subset of miRNAs by facilitating the cleavage reaction by Drosha. The mechanism that limits Smad-mediated processing to a selective group of miRNAs remained hitherto unexplored. In this study, we expand the number of TGFbeta/BMP-regulated miRNAs (T/B-miRs) to 20.

Regulation of pri-miRNA processing through Smads.

microRNAs (miRNAs) are small (-22 nucleotides (nt)), noncoding RNAs that play a critical role in diverse biological functions by modulating mRNA stability and translational control. Numerous miRNA profiling studies have indicated that the levels of miRNAs are tightly controlled during developmental stages and various pathophysiological and physiological conditions. Following transcription, the long primary miRNA transcript undergoes a series of coordinated maturation steps to generate the mature miRNA.

Molecular basis for antagonism between PDGF and the TGFbeta family of signalling pathways by control of miR-24 expression.

Modulation of the vascular smooth-muscle-cell (vSMC) phenotype from a quiescent 'contractile' phenotype to a proliferative 'synthetic' phenotype has been implicated in vascular injury repair, as well as pathogenesis of vascular proliferative diseases. Both bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFbeta)-signalling pathways promote a contractile phenotype, while the platelet-derived growth factor-BB (PDGF-BB)-signalling pathway promotes a switch to the synthetic phenotype. Here we show that PDGF-BB induces microRNA-24 (miR-24), which in turn leads to downregulation of Tribbles-like protein-3 (Trb3).

Control of microRNA biogenesis by TGFbeta signaling pathway-A novel role of Smads in the nucleus.

microRNAs (miRNAs) are small, non-coding RNAs that modulate diverse biological functions through the repression of target genes. miRNA profiling studies have indicated that the levels of miRNAs are altered during normal development and pathogenesis of various diseases, including cancer and cardiovascular disorders. The signaling pathways which control miRNA biogenesis and the mechanisms of regulation, however, are not well understood.

Regulation of MicroRNA Biogenesis: A miRiad of mechanisms.

microRNAs are small, non-coding RNAs that influence diverse biological functions through the repression of target genes during normal development and pathological responses. Widespread use of microRNA arrays to profile microRNA expression has indicated that the levels of many microRNAs are altered during development and disease. These findings have prompted a great deal of investigation into the mechanism and function of microRNA-mediated repression.

Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype.

The platelet-derived growth factor (PDGF) signaling pathway is a critical regulator of animal development and homeostasis. Activation of the PDGF pathway leads to neointimal proliferative responses to artery injury; it promotes a switch of vascular smooth muscle cells (vSMC) to a less contractile phenotype by inhibiting the SMC-specific gene expression and increasing the rate of proliferation and migration. The molecular mechanism for these pleiotropic effects of PDGFs has not been fully described.

Drug-susceptible HIV-1 infection despite intermittent fixed-dose combination tenofovir/emtricitabine as prophylaxis is associated with low-level viremia, delayed seroconversion, and an attenuated clinical course.

Background: Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC).

SMAD proteins control DROSHA-mediated microRNA maturation.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA and protein synthesis. Aberrant miRNA expression leads to developmental abnormalities and diseases, such as cardiovascular disorders and cancer; however, the stimuli and processes regulating miRNA biogenesis are largely unknown. The transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) family of growth factors orchestrates fundamental biological processes in development and in the homeostasis of adult tissues, including the vasculature.

Control of phenotypic plasticity of smooth muscle cells by bone morphogenetic protein signaling through the myocardin-related transcription factors.

Vascular smooth muscle cells (VSMCs), unlike other muscle cells, do not terminally differentiate. In response to injury, VSMCs change phenotype, proliferate, and migrate as part of the repair process. Dysregulation of this plasticity program contributes to the pathogenesis of several vascular disorders, such as atherosclerosis, restenosis, and hypertension.

A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor.

Bone morphogenetic protein (BMP) signaling regulates many different biological processes, including cell growth, differentiation, and embryogenesis. BMPs bind to heterogeneous complexes of transmembrane serine/threonine (Ser/Thr) kinase receptors known as the BMP type I and II receptors (BMPRI and BMPRII). BMPRII phosphorylates and activates the BMPRI kinase, which in turn activates the Smad proteins.

Allelic variation on chromosome 5 controls beta-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice.

Leptin signaling is a critical component of normal insulin sensitivity. Overt hyperglycemia and type 2 diabetes mellitus can be manifested in states of leptin signaling deficiencies by the additional effects of other genetic factors. We have previously described the contrasting insulin sensitivities and glycemic states of two congenic diabetes (db/db) mouse strains.