321 research outputs found

    Palestinian children's experiences of drug abuse in the home in the Occupied Territories of Palestine: A scoping review of extant literature

    Get PDF
    The Occupied Territories of Palestine (OtP) consists of the non-contiguous West Bank including East Jerusalem, and the Gaza Strip. Its dense population with political and economic tensions is affected by a rise in drug trafficking, abuse and addiction. A scoping review mapped what is known about Palestinian children's experiences of drug abuse in the home. Following application of exclusion measures, six records remained. Charting and analysis resulted in three themes; The consequences of being a child with a drug using parent; Causal factors of drug use in Palestinian families; and Prevalence rates of parental drug use are unknown. The review paints a concerning picture of stigma, family dysfunction, school drop-out, child and family isolation and maladaptive child development. Exposure to drugs, trauma and abuse contributes to strong potential for Palestinian child drug use, sexual exploitation, overdose, psychiatric illness, and infectious diseases acquisition. The review will inform the urgent strategic response

    Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems

    Get PDF
    The PgIB oligosaccharyltransferase (OTase) of Campylobacter jejuni can be functionally expressed in Escherichia coli, and its relaxed oligosaccharide substrate specificity allows the transfer of different glycans from the lipid carrier undecaprenyl pyrophosphate to an acceptor protein. To investigate the substrate specificity of PgIB, we tested the transfer of a set of lipid-linked polysaccharides in E. coli and Salmonella enterica serovar Typhimurium. A hexose linked to the C-6 of the monosaccharide at the reducing end did not inhibit the transfer of the O antigen to the acceptor protein. However, PgIB required an acetamido group at the C-2. A model for the mechanism of PgIB involving this functional group was proposed. Previous experiments have shown that eukaryotic OTases have the same requirement, suggesting that eukaryotic and prokaryotic OTases catalyze the transfer of oligosaccharides by a conserved mechanism. Moreover, we demonstrated the functional transfer of the C. jejuni glycosylation system into S. enterica. The elucidation of the mechanism of action and the substrate specificity of PgIB represents the foundation for engineering glycoproteins that will have an impact on biotechnology

    Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

    Get PDF
    Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

    Clinical and physiological effects of transcranial electrical stimulation position on motor evoked potentials in scoliosis surgery

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>During intraoperative monitoring for scoliosis surgery, we have previously elicited ipsilateral and contralateral motor evoked potentials (MEP) with cross scalp stimulation. Ipsilateral MEPs, which may have comprised summation of early ipsilaterally conducted components and transcallosally or deep white matter stimulated components, can show larger amplitudes than those derived purely from contralateral motor cortex stimulation. We tested this hypothesis using two stimulating positions. We compared intraoperative MEPs in 14 neurologically normal subjects undergoing scoliosis surgery using total intravenous anesthetic regimens.</p> <p>Methods</p> <p>Trancranial electrical stimulation was applied with both cross scalp (C3C4 or C4C3) or midline (C3Cz or C4Cz) positions. The latter was assumed to be more focal and result in little transcallosal/deep white matter stimulation. A train of 5 square wave stimuli 0.5 ms in duration at up to 200 mA was delivered with 4 ms (250 Hz) interstimulus intervals. Averaged supramaximal MEPs were obtained from the tibialis anterior bilaterally.</p> <p>Results</p> <p>The cross scalp stimulating position resulted in supramaximal MEPs that were of significantly higher amplitude, shorter latency and required lower stimulating intensity to elicit overall (Wilcoxon Signed Rank test, p < 0.05 for all), as compared to the midline stimulating position. However, no significant differences were found for all 3 parameters comparing ipsilaterally and contralaterally recorded MEPs (p > 0.05 for all), seen for both stimulating positions individually.</p> <p>Conclusions</p> <p>Our findings suggest that cross scalp stimulation resulted in MEPs obtained ipsilaterally and contralaterally which may be contributed to by summation of ipsilateral and simultaneous transcallosally or deep white matter conducted stimulation of the opposite motor cortex. Use of this stimulating position is advocated to elicit MEPs under operative circumstances where anesthetic agents may cause suppression of cortical and spinal excitability. Although less focal in nature, cross scalp stimulation would be most suitable for infratentorial or spinal surgery, in contrast to supratentorial neurosurgical procedures.</p

    PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

    Get PDF
    The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

    Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery

    Get PDF
    Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring

    Simple synthesis of 32P-labelled inositol hexakisphosphates for study of phosphate transformations

    Get PDF
    In many soils inositol hexakisphosphate in its various forms is as abundant as inorganic phosphate. The organismal and geochemical processes that exchange phosphate between inositol hexakisphosphate and other pools of soil phosphate are poorly defined, as are the organisms and enzymes involved. We rationalized that simple enzymic synthesis of inositol hexakisphosphate labeled with 32P would greatly enable study of transformation of soil inositol phosphates when combined with robust HPLC separations of different inositol phosphates

    Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

    Get PDF
    Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.National Institutes of Health (U.S.)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMS) (K08-AR054615))National Cancer Institute (U.S.) (NIH/(NCI) (R01-CA118750))National Cancer Institute (U.S.) (NIH/(NCI) R01-CA130795))Juvenile Diabetes Research Foundation InternationalAmerican Cancer SocietyHoward Hughes Medical Institute (Early career scientist)Stanford University (Graduate Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship

    The genomes of two key bumblebee species with primitive eusocial organization

    Get PDF
    Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

    Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

    Get PDF
    Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an
    corecore