Localized reversible nanoscale phase separation in Pr_0.63Ca_0.37MnO_3 single crystal using a scanning tunneling microscope tip

We report the destabilization of the charge ordered insulating (COI) state in a localized region of Pr_0.63Ca_0.37MnO_3 single crystal by current injection using a scanning tunneling microscope tip. This leads to controlled phase separation and formation of localized metallic nanoislands in the COI matrix which have been detected by local tunneling conductance mapping. The metallic regions thus created persist even after reducing the injected current to lower values. The original conductance state can be restored by injecting a current of similar magnitude but of opposite polarity. We thus achieve reversible nanoscale phase separation that gives rise to the possibility to "write, read, and erase" nanosized conducting regions in an insulating matrix with high spatial resolution.Comment: 8 pages, 4 figures, Appl. Phys. Lett (accepted for publication

CONVENTIONAL AYURVEDIC MANAGEMENT IN SPASTIC CEREBRAL PALSY: A CASE STUDY

Cerebral palsy is a non-progressive but crippling neurological disorder in children. The prevalence rate of cerebral palsy has risen to well above two per thousand life birth. Spastic cerebral palsy is a disorder that causes muscle tightness. This condition prevents the normal development of motor function. It makes up over 70% of all cases of cerebral palsy. As per Ayurvedic classics, the spasticity is termed as Jadatwam and is one of the Vatha predominant Lakshana. The important causative factors are the improper diet and regimen followed during pregnancy, Akalapravahanam (untimely contractures during labour), head injury during delivery, Garbha sosham (Intrauterine Growth Retardation) etc. Due to these aetiology Dhadhu, Kshaya occurs followed by Vata dosha prakopa and produces symptoms like Praseka, Sosha, Jadatwam etc. In this study, based on the concept of Vathavyadhi chikitsa, Snehana, Swedana, Sodhana and Brimhana therapy with appropriate Panchkarma procedure was done. Physiotherapy was provided along with treatment, it helped to improve motor functions and activities of daily living of the patient. The spasticity was assessed through the range of motion of joints (ROM) by using the instrument Goniometer while the motor and mental developments were assessed by developmental assessment scales for Indian infants (DASII). Considering the ROM of joints of upper and lower limb, spasticity was reduced in the extension movement of the ankle, hip, knee, elbow, and shoulder. The motor and mental developmental quotient of the baby was improved after the treatment. This article is an attempt to highlight the efficacy of conventional Ayurvedic management in spastic cerebral palsy with Kerala specialties

A Comparative Analysis of the Metabolomic Response of Electron Beam Inactivated E. coli O26:H11 and Salmonella Typhimurium ATCC 13311

Ionizing radiation such as Electron beam (EB) and gamma irradiation inactivate microbial cells preventing their multiplication. These cells, however, are structurally intact and appear to have residual metabolic activity. We were interested in understanding the metabolic pathways that were still functional in EB-inactivated cells. Therefore, the primary objective of this study was to compare the metabolites accumulating in EB-inactivated pathogens E. coli 026:H11 and S. Typhimurium immediately after EB inactivation and 24 h post inactivation. Defined aliquots (109 CFU/mL) of E. coli O26-H11 (TW 1597) and S. Typhimurium (ATCC 13311) suspended in phosphate-buffered saline were exposed to lethal EB doses of 3 kGy and 2 kGy, respectively. Complete inactivation (inability of cells to multiply) was confirmed by traditional plating methods. An untargeted analysis of the primary metabolites accumulating in un-irradiated (control) cells, EB-inactivated cells immediately after irradiation, and EB-inactivated cells that were incubated at room temperature for 24 h post EB inactivation was performed using gas chromatography/mass spectrometry. A total of 349 different metabolites were detected in the EB-inactivated S. Typhimurium and E. coli O26:H11 cells, out of which, only 50% were identifiable. In S. Typhimurium, 98 metabolites were expressed at statistically different concentrations (P < 0.05) between the three treatment groups. In E. coli O26:H11, 63 metabolites were expressed at statistically different concentrations (P < 0.05) between the three treatment groups. In both these pathogens, the β-alanine, alanine, aspartate, and glutamate metabolic pathways were significantly impacted (P < 0.01). Furthermore, the metabolomic changes in EB-inactivated cells were amplified significantly after 24 h storage at room temperature in phosphate-buffered saline. These results suggest that EB-inactivated cells are very metabolically active and, therefore, the term Metabolically Active yet Non-culturable is an apt term describing EB-inactivated bacterial cells

NRP2 transcriptionally regulates its downstream effector WDFY1.

Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, essential for promotion of oncogenic activation and cancer cell survival. Here, we have delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our results indicated that NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells. Thus, inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce cell death in metastatic cancer

Prion-like proteins sequester and suppress the toxicity of huntingtin exon 1

Expansions of preexisting polyglutamine (polyQ) tracts in at least nine different proteins cause devastating neurodegenerative diseases. There are many unique features to these pathologies, but there must also be unifying mechanisms underlying polyQ toxicity. Using a polyQ-expanded fragment of huntingtin exon-1 (Htt103Q), the causal protein in Huntington disease, we and others have created tractable models for investigating polyQ toxicity in yeast cells. These models recapitulate key pathological features of human diseases and provide access to an unrivalled genetic toolbox. To identify toxicity modifiers, we performed an unbiased overexpression screen of virtually every protein encoded by the yeast genome. Surprisingly, there was no overlap between our modifiers and those from a conceptually identical screen reported recently, a discrepancy we attribute to an artifact of their overexpression plasmid. The suppressors of Htt103Q toxicity recovered in our screen were strongly enriched for glutamine- and asparagine-rich prion-like proteins. Separated from the rest of the protein, the prion-like sequences of these proteins were themselves potent suppressors of polyQ-expanded huntingtin exon-1 toxicity, in both yeast and human cells. Replacing the glutamines in these sequences with asparagines abolished suppression and converted them to enhancers of toxicity. Replacing asparagines with glutamines created stronger suppressors. The suppressors (but not the enhancers) coaggregated with Htt103Q, forming large foci at the insoluble protein deposit in which proteins were highly immobile. Cells possessing foci had fewer (if any) small diffusible oligomers of Htt103Q. Until such foci were lost, cells were protected from death. We discuss the therapeutic implications of these findings.Howard Hughes Medical InstituteNational Institutes of Health (U.S.) (Grant GM25874)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)G. Harold and Leila Y. Mathers FoundationBeckman Laser Institute FoundationEleanor Schwartz Charitable FoundationWhitehead Institute for Biomedical Researc

The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort.

ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01).InterpretationPPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials

Factors Related to Female Sex Workers’ Willingness to Utilize VCT Service: A Qualitative Study in Jinan City, Northern China

While national HIV prevalence remains low in China, female sex workers (FSWs) have become infected at high rates. Free voluntary HIV counseling and testing (VCT) has been offered in recent years; however, its utilization rate is low. This study explored factors related to FSWs' willingness to utilize a VCT clinic. Qualitative interviews informed by the Ecological Perspective were conducted to interview 17 FSWs and 12 managers from 23 selected entertainment establishments in Jinan, the capital of Shandong province in northern China. While the majority of FSWs professed willingness to use VCT services, they described barriers to actual utilization of services which included: misunderstandings about HIV; low perceived risk and HIV prevalence; mistrust of the free VCT; and especially anxiety about the implications of possible test results. This research suggests that increasing FSWs' utilization of VCT will require increased knowledge of HIV and VCT, and acceptance of testing and on-site VCT services

Factors Associated with Utilization of a Free HIV VCT Clinic by Female Sex Workers in Jinan City, Northern China

Based on our previous qualitative exploration, this research presents the second phase in our study of factors associated with utilization of a free HIV VCT clinic in Jinan City, Northern China, by female sex workers (FSWs). A total of 970 FSWs from entertainment venues were interviewed and prospectively followed to determine who ultimately sought and received VCT at the clinic, compared to those who did not. Simple and multiple logistic regressions were performed on factors drawn from the Ecological Perspective, hypothesized to be associated with utilization of testing at the VCT clinic. Despite 69% of FSWs expressing willingness to attend the VCT clinic, only 11% were actually tested. The multiple logistic regression model that provided best goodness of fit included the covariates of willingness to attend the VCT clinic (Adjusted OR 3.13, 95% CI: 1.62–6.59), low perceived HIV infection risk (Adjusted OR 0.64, 95% CI: 0.35–1.11), low fear of FSWs status disclosure in the clinic (Adjusted OR 0.55, 95% CI: 0.31–0.94) and influence of acquaintances (Adjusted OR 0.52, 95% CI: 0.29–0.89) and peers (Adjusted OR 2.45, 95% CI: 1.40–4.50). This is the first study in China to follow FSWs longitudinally to measure factors related to VCT utilization. The low utilization of VCT services by participants in our study is similar to prior reports throughout China. FSWs’ access to VCT service is associated with intrapersonal, institutional, and particularly, interpersonal factors. Based on these findings, we recommend emphasis on confidentiality of services, VCT education for influential peers, and introduction of HIV rapid testing on site

Socio-demographic and AIDS-related factors associated with tuberculosis stigma in southern Thailand: a quantitative, cross-sectional study of stigma among patients with TB and healthy community members

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB) remains one of the most important infectious diseases worldwide. A comprehensive approach towards disease control that addresses social factors including stigma is now advocated. Patients with TB report fears of isolation and rejection that may lead to delays in seeking care and could affect treatment adherence. Qualitative studies have identified socio-demographic, TB knowledge, and clinical determinants of TB stigma, but only one prior study has quantified these associations using formally developed and validated stigma scales. The purpose of this study was to measure TB stigma and identify factors associated with TB stigma among patients and healthy community members.</p> <p>Methods</p> <p>A cross-sectional study was performed in southern Thailand among two different groups of participants: 480 patients with TB and 300 healthy community members. Data were collected on socio-demographic characteristics, TB knowledge, and clinical factors. Scales measuring perceived TB stigma, experienced/felt TB stigma, and perceived AIDS stigma were administered to patients with TB. Community members responded to a community TB stigma and community AIDS stigma scale, which contained the same items as the perceived stigma scales given to patients. Stigma scores could range from zero to 30, 33, or 36 depending on the scale. Three separate multivariable linear regressions were performed among patients with TB (perceived and experience/felt stigma) and community members (community stigma) to determine which factors were associated with higher mean TB stigma scores.</p> <p>Results</p> <p>Only low level of education, belief that TB increases the chance of getting AIDS, and AIDS stigma were associated with higher TB stigma scores in all three analyses. Co-infection with HIV was associated with higher TB stigma among patients. All differences in mean stigma scores between index and referent levels of each factor were less than two points, except for incorrectly believing that TB increases the chance of getting AIDS (mean difference of 2.16; 95% CI: 1.38, 2.94) and knowing someone who died from TB (mean difference of 2.59; 95% CI: 0.96, 4.22).</p> <p>Conclusion</p> <p>These results suggest that approaches addressing the dual TB/HIV epidemic may be needed to combat TB stigma and that simply correcting misconceptions about TB may have limited effects.</p