Regulation of murine cytochrome c oxidase Vb gene expression during myogenesis: YY-1 and heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP1) reciprocally regulate transcription activity by physical interaction with the BERF-1/ZBP-89 factor.

A transcription suppressor element (sequence -481 to -320) containing a G-rich motif (designated GTG) and a newly identified CAT-rich motif (designated CATR) was previously shown to modulate expression of the mouse cytochrome c oxidase Vb gene during myogenesis. Here, we show that the GTG element is critical for transcription activation in both undifferentiated and differentiated myocytes. Mutations of the CATR motif abolished transcription repression in myoblasts while limiting transcription activation in differentiated myotubes, suggesting contrasting functional attributes of this DNA motif at different stages of myogenesis. Results show that the activity of the transcription suppressor motif is modulated by an orchestrated interplay between ubiquitous transcription factors: ZBP-89, YY-1, and a member of the heterogeneous nuclear ribonucleoprotein D-like protein (also known as JKTBP1) family. In undifferentiated muscle cells, GTG motif-bound ZBP-89 physically and functionally interacted with CATR motif-bound YY-1 to mediate transcription repression. In differentiated myotubes, heterogeneous nuclear ribonucleoprotein D-like protein/JKTBP1 bound to the CATR motif exclusive of YY-1 and interacted with ZBP-89 in attenuating repressor activity, leading to transcription activation. Our results show a novel mechanism of protein factor switching in transcription regulation of the cytochrome c oxidase Vb gene during myogenesis

Characterization of a new molecule capable of inhibiting several steps of the amyloid cascade in Alzheimer's disease

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in elderly people. Existent therapies are directed at alleviating some symptoms, but are not effective in altering the course of the disease. Methods: Based on our previous study that showed that an Fiji-interacting small peptide protected against the toxic effects of amyloid-beta peptide (A beta), we carried out an array of in silico, in vitro, and in vivo assays to identify a molecule having neuroprotective properties. Results: In silico studies showed that the molecule, referred to as M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine), was able to interact with the A beta peptide. Additionally, in vitro assays showed that M30 blocked A beta aggregation, association to the plasma membrane, synaptotoxicity, intracellular calcium, and cellular toxicity, while in vivo experiments demonstrated that M30 induced a neuroprotective effect by decreasing the toxicity of A beta in the dentate gyrus of the hippocampus and improving the alteration in spatial memory in behavior assays. Discussion Therefore, we propose that this new small molecule could be a useful candidate for the additional development of a treatment against AD since it appears to block multiple steps in the amyloid cascade. Overall, since there are no drugs that effectively block the progression of AD, this approach represents an innovative strategy. Significance: Currently, there is no effective treatment for AD and the expectations to develop an effective therapy are low. Using in silico, in vitro, and in vivo experiments, we identified a new compound that is able to inhibit A beta-induced neurotoxicity, specifically aggregation, association to neurons, synaptic toxicity, calcium dyshomeostasis and memory impairment induced by A beta. Because A beta toxicity is central to AD progression, the inhibition mediated by this new molecule might be useful as a therapeutic tool

Assessment of the scale, coverage and outcomes of the Avahan HIV prevention program for female sex workers in Tamil Nadu, India: is there evidence of an effect?

<p>Abstract</p> <p>Background</p> <p>Avahan, the India AIDS Initiative, a large-scale HIV prevention program, using peer-mediated approaches and STI services, was implemented for high-risk groups for HIV in six states in India. This paper describes the assessment of the program among female sex workers (FSWs) in the southern state of Tamil Nadu.</p> <p>Methods</p> <p>An analytical framework based on the Avahan impact evaluation design was used. Routine program monitoring data, two rounds of cross-sectional biological and behavioural surveys among FSWs in 2006 (Round 1) and 2009 (Round 2) and quality assessments of clinical services for sexually transmitted infections (STIs) were used to assess trends in coverage, condom use and prevalence of STIs, HIV and their association with program exposure. Logistic regression analysis was used to examine trends in intermediate outcomes and their associations with intervention exposure.</p> <p>Results</p> <p>The Avahan program in Tamil Nadu was scaled up and achieved monthly reported coverage of 79% within four years of implementation. The cross-sectional survey data showed an increasing proportion of FSWs being reached by Avahan, 54% in Round 1 and 86% in Round 2 [AOR=4.7;p=0.001]. Quality assessments of STI clinical services showed consistent improvement in quality scores (3.0 in 2005 to 4.5 in 2008). Condom distribution by the program rose to cover all estimated commercial sex acts. Reported consistent condom use increased between Round 1 and Round 2 with occasional (72% to 93%; AOR=5.5; p=0.001) and regular clients (68% to 89%; AOR=4.3; p=0.001) while reactive syphilis serology declined significantly (9.7% to 2.2% AOR=0.2; p=0.001). HIV prevalence remained stable at 6.1% between rounds. There was a strong association between Avahan exposure and consistent condom use with commercial clients; however no association was seen with declines in STIs.</p> <p>Conclusions</p> <p>The Avahan program in Tamil Nadu achieved high coverage of FSWs, resulting in outcomes of improved condom use, declining syphilis and stabilizing HIV prevalence. These expected outcomes following the program logic model and declining HIV prevalence among general population groups suggest potential impact of high risk group interventions on HIV epidemic in Tamil Nadu.</p

Permanent Lattice Compression of Lead-Halide Perovskite for Persistently Enhanced Optoelectronic Properties

Under mild mechanical pressure, halide perovskites show enhanced optoelectronic properties. However, these improvements are reversible upon decompression, and permanent enhancements have yet to be ..

Identification of mungbean lines with tolerance or resistance to yellow mosaic in fields in India where different begomovirus species and different Bemisia tabaci cryptic species predominate

Mungbean (Vigna radiata (L.) Wilczek) is an important pulse crop in India. A major constraint for improved productivity is the yield loss caused by mungbean yellow mosaic disease (MYMD). This disease is caused by several begomoviruses which are transmitted by the whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). The objective of this study was to identify the predominant begomoviruses infecting mungbean and the major cryptic species of B. tabaci associated with this crop in India. The indigenous B. tabaci cryptic species Asia II 1 was found dominant in Northern India, whereas Asia II 8 was found predominant in Southern India. Repeated samplings over consecutive years indicate a stable situation with, Mungbean yellow mosaic virus strains genetically most similar to a strain from urdbean (MYMV-Urdbean) predominant in North India, strains most similar to MYMV-Vigna predominant in South India, and Mungbean yellow mosaic India virus (MYMIV) strains predominant in Eastern India. In field studies, mungbean line NM 94 showed a high level of tolerance to the disease in the Eastern state of Odisha where MYMIV was predominant and in the Southern state of Andhra Pradesh where MYMV-Vigna was predominant, but only a moderate level of tolerance in the Southern state of Tamil Nadu. However, in Northern parts of India where there was high inoculum pressure of MYMV-Urdbean during the Kharif season, NM 94 developed severe yellow mosaic symptoms. The identification of high level of tolerance in mungbean lines such as ML 1628 and of resistance in black gram and rice bean provides hope for tackling the disease through resistance breeding

Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo

A selective tagging method for detecting minor alternatively-localized populations of a protein is used to study a disease-associated transmembrane form of prion protein. The analysis reveals key features of transmembrane prion protein metabolism and one way this is altered by human disease-causing mutants

Dysregulation of neuronal iron homeostasis as an alternative unifying effect of mutations causing familial Alzheimer's disease

The overwhelming majority of dominant mutations causing early onset familial Alzheimer's disease (EOfAD) occur in only three genes, PSEN1, PSEN2, and APP. An effect-in-common of these mutations is alteration of production of the APP-derived peptide, amyloid ß (Aß). It is this key fact that underlies the authority of the Amyloid Hypothesis that has informed Alzheimer's disease research for over two decades. Any challenge to this authority must offer an alternative explanation for the relationship between the PSEN genes and APP. In this paper, we explore one possible alternative relationship - the dysregulation of cellular iron homeostasis as a common effect of EOfAD mutations in these genes. This idea is attractive since it provides clear connections between EOfAD mutations and major characteristics of Alzheimer's disease such as dysfunctional mitochondria, vascular risk factors/hypoxia, energy metabolism, and inflammation. We combine our ideas with observations by others to describe a "Stress Threshold Change of State" model of Alzheimer's disease that may begin to explain the existence of both EOfAD and late onset sporadic (LOsAD) forms of the disease. Directing research to investigate the role of dysregulation of iron homeostasis in EOfAD may be a profitable way forward in our struggle to understand this form of dementia