Mercury in Nelson's Sparrow Subspecies at Breeding Sites

Background: Mercury is a persistent, biomagnifying contaminant that can cause negative effects on ecosystems. Marshes are often areas of relatively high mercury methylation and bioaccumulation. Nelson’s Sparrows (Ammodramus nelsoni) use marsh habitats year-round and have been documented to exhibit tissue mercury concentrations that exceed negative effects thresholds. We sought to further characterize the potential risk of Nelson’s Sparrows to mercury exposure by sampling individuals from sites within the range of each of its subspecies

Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs

The global pendulum swing towards community health workers in low- and middle-income countries: A scoping review of trends, geographical distribution and programmatic orientations, 2005 to 2014

BACKGROUND: There has been a substantial increase in publications and interest in community health workers (CHWs) in low- and middle-income countries (LMIC) over the last years. This paper examines the growth, geographical distribution and programmatic orientations of the indexed literature on CHWs in LMIC over a 10-year period. METHODS: A scoping review of publications on CHWs from 2005 to 2014 was conducted. Using an inclusive list of terms, we searched seven databases (including MEDLINE, CINAHL, Cochrane) for all English-language publications on CHWs in LMIC. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. These were coded in an Excel spreadsheet by year, type of publication (e.g. review, empirical), country, region, programmatic orientation (e.g. maternal-child health, HIV/AIDS, comprehensive) and CHW roles (e.g. prevention, treatment) and further analysed in Stata14. Drawing principally on the subset of review articles, specific roles within programme areas were identified and grouped. FINDINGS: Six hundred seventy-eight publications from 46 countries on CHWs were inventoried over the 10-year period. There was a sevenfold increase in annual number of publications from 23 in 2005 to 156 in 2014. Half the publications were reporting on initiatives in Africa, a third from Asia and 11 % from the Americas (mostly Brazil). The largest single focus and driver of the growth in publications was on CHW roles in meeting the Millennium Development Goals of maternal, child and neonatal survival (35 % of total), followed by HIV/AIDS (16 %), reproductive health (6 %), non-communicable diseases (4 %) and mental health (4 %). Only 17 % of the publications approached CHW roles in an integrated fashion. There were also distinct regional (and sometimes country) profiles, reflecting different histories and programme traditions. CONCLUSIONS: The growth in literature on CHWs provides empirical evidence of ever-increasing expectations for addressing health burdens through community-based action. This literature has a strong disease- or programme-specific orientation, raising important questions for the design and sustainable delivery of integrated national programmes.Scopu

Transcription, Epigenetics and Ameliorative Strategies in Huntington’s Disease: a Genome-Wide Perspective

ease (HD) is an early event that shapes the brain transcriptome by both the depletion and ectopic activation of gene products that eventually affect survival and neuronal functions. Disrup-tion in the activity of gene expression regulators, such as transcription factors, chromatin-remodeling proteins, and non-coding RNAs, accounts for the expression changes observed in multiple animal and cellular models of HD and in samples from patients. Here, I review the recent advances in the study of HD transcriptional dysregulation and its causes to finally discuss the possible implications in ameliorative strategies from a genome-wide perspective. To date, the use of genome-wide approaches, predominantly based on microar-ray platforms, has been successful in providing an extensive catalog of differentially regulated genes, including biomarkers aimed at monitoring the progress of the pathology. Although still incipient, the introduction of combined next-generation sequencing techniques is enhancing our comprehension of the mechanisms underlying altered transcriptional dysregulation in HD by providing the first genomic landscapes associated with epigenetics and the occupancy of transcription factors. In addition, the use of genome-wide approaches is becoming more and more necessary to evaluate the efficacy and safety of ameliorative strategies and to identify novel mechanisms of amelioration that may help in the improvement of current preclinical therapeutics. Finally, the major conclusions obtain-ed from HD transcriptomics studies have the potential to be extrapolated to other neurodegenerative disorders

Deterministic and robust room-temperature exchange coupling in monodomain multiferroic BiFeO3 heterostructures

Exploiting multiferroic BiFeO3 thin films in spintronic devices requires deterministic and robust control of both internal magnetoelectric coupling in BiFeO3, as well as exchange coupling of its antiferromagnetic order to a ferromagnetic overlayer. Previous reports utilized approaches based on multi-step ferroelectric switching with multiple ferroelectric domains. Because domain walls can be responsible for fatigue, contain localized charges intrinsically or via defects, and present problems for device reproducibility and scaling, an alternative approach using a monodomain magnetoelectric state with single-step switching is desirable. Here we demonstrate room temperature, deterministic and robust, exchange coupling between monodomain BiFeO3 films and Co overlayer that is intrinsic (i.e., not dependent on domain walls). Direct coupling between BiFeO3 antiferromagnetic order and Co magnetization is observed, with ~ 90° in-plane Co moment rotation upon single-step switching that is reproducible for hundreds of cycles. This has important consequences for practical, low power non-volatile magnetoelectric devices utilizing BiFeO3