Agricultural matrices affect ground ant assemblage composition inside forest fragments

© 2018 Assis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The establishment of agricultural matrices generally involves deforestation, which leads to fragmentation of the remaining forest. This fragmentation can affect forest dynamics both positively and negatively. Since most animal species are affected, certain groups can be used to measure the impact of such fragmentation. This study aimed to measure the impacts of agricultural crops (matrices) on ant communities of adjacent lower montane Atlantic rainforest fragments. We sampled nine forest fragments at locations surrounded by different agricultural matrices, namely: coffee (3 replicates); sugarcane (3); and pasture (3). At each site we installed pitfall traps along a 500 m transect from the interior of the matrix to the interior of the fragment (20 pitfall traps ~25 m apart). Each transect was partitioned into four categories: interior of the matrix; edge of the matrix; edge of the fragment; and interior of the fragment. For each sample site, we measured ant species richness and ant community composition within each transect category. Ant richness and composition differed between fragments and matrices. Each sample location had a specific composition of ants, probably because of the influence of the nature and management of the agricultural matrices. Species composition in the coffee matrix had the highest similarity to its corresponding fragment. The variability in species composition within forest fragments surrounded by pasture was greatest when compared with forest fragments surrounded by sugarcane or, to a lesser extent, coffee. Functional guild composition differed between locations, but the most representative guild was ‘generalist’ both in the agricultural matrices and forest fragments. Our results are important for understanding how agricultural matrices act on ant communities, and also, how these isolated forest fragments could act as an island of biodiversity in an ‘ocean of crops’

Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations.

Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause frontotemporal dementia in GRN mutation carriers. Progranulin haploinsufficiency may drive frontotemporal dementia pathogenesis by disrupting lysosomal function, as patients with GRN mutations on both alleles develop the lysosomal storage disorder neuronal ceroid lipofuscinosis, and frontotemporal dementia patients with GRN mutations (FTD-GRN) also accumulate lipofuscin. The specific lysosomal deficits caused by progranulin insufficiency remain unclear, but emerging data indicate that progranulin insufficiency may impair lysosomal sphingolipid-metabolizing enzymes. We investigated the effects of progranulin insufficiency on sphingolipid-metabolizing enzymes in the inferior frontal gyrus of FTD-GRN patients using fluorogenic activity assays, biochemical profiling of enzyme levels and posttranslational modifications, and quantitative neuropathology. Of the enzymes studied, only β-glucocerebrosidase exhibited impairment in FTD-GRN patients. Brains from FTD-GRN patients had lower activity than controls, which was associated with lower levels of mature β-glucocerebrosidase protein and accumulation of insoluble, incompletely glycosylated β-glucocerebrosidase. Immunostaining revealed loss of neuronal β-glucocerebrosidase in FTD-GRN patients. To investigate the effects of progranulin insufficiency on β-glucocerebrosidase outside of the context of neurodegeneration, we investigated β-glucocerebrosidase activity in progranulin-insufficient mice. Brains from Grn-/- mice had lower β-glucocerebrosidase activity than wild-type littermates, which was corrected by AAV-progranulin gene therapy. These data show that progranulin insufficiency impairs β-glucocerebrosidase activity in the brain. This effect is strongest in neurons and may be caused by impaired β-glucocerebrosidase processing

Disk galaxies are self-similar: the universality of the HI-to-Halo mass ratio for isolated disks

Observed scaling relations in galaxies between baryons and dark matter global properties are key to shed light on the process of galaxy formation and on the nature of dark matter. Here, we study the scaling relation between the neutral hydrogen (HI) and dark matter mass in isolated rotationally-supported disk galaxies at low redshift. We first show that state-of-the-art galaxy formation simulations predict that the HI-to-dark halo mass ratio decreases with stellar mass for the most massive disk galaxies. We then infer dark matter halo masses from high-quality rotation curve data for isolated disk galaxies in the local Universe, and report on the actual universality of the HI-to-dark halo mass ratio for these observed galaxies. This scaling relation holds for disks spanning a range of 4 orders of magnitude in stellar mass and 3 orders of magnitude in surface brightness. Accounting for the diversity of rotation curve shapes in our observational fits decreases the scatter of the HI-to-dark halo mass ratio while keeping it constant. This finding extends the previously reported discrepancy for the stellar-to-halo mass relation of massive disk galaxies within galaxy formation simulations to the realm of neutral atomic gas. Our result reveals that isolated galaxies with regularly rotating extended HI disks are surprisingly self-similar up to high masses, which hints at mass-independent self-regulation mechanisms that have yet to be fully understood.Comment: 14 pages, 4 figures. Accepted for publication in ApJ

Chronic Morphine Alters the Presynaptic Protein Profile: Identification of Novel Molecular Targets Using Proteomics and Network Analysis

Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence

The XMM-Newton wide angle survey (XWAS): the X-ray spectrum of type-1 AGN

Aims. We discuss the broad band X-ray properties of one of the largest samples of X-ray selected type-1 AGN to date (487 objects in total), drawn from the XMM-Newton Wide Angle Survey (XWAS). The objects presented in this work cover 2−10 keV (rest-frame) luminosities from ∼1042−1045 erg s−1 and are detected up to redshift ∼4. We constrain the overall properties of the broad band continuum, soft excess and X-ray absorption, along with their dependence on the X-ray luminosity and redshift.We discuss the implications for models of AGN emission. Methods. We fitted the observed 0.2−12 keV broad band spectra with various models to search for X-ray absorption and soft excess. The F-test was used with a significance threshold of 99% to statistically accept the detection of additional spectral components. Results. We constrained the mean spectral index of the broad band X-ray continuum to (Γ) = 1.96 ± 0.02 with intrinsic dispersion σ(Γ) = 0.27+0.01 −0.02. The continuum becomes harder at faint fluxes and at higher redshifts and hard (2−10 keV) luminosities. The dependence of Γ with flux is likely due to undetected absorption rather than to spectral variation. We found a strong dependence of the detection efficiency of objects on the spectral shape. We expect this effect to have an impact on the measured mean continuum shapes of sources at different redshifts and luminosities. We detected excess absorption in >∼3% of our objects, with rest-frame column densities ∼a few ×1022 cm−2. The apparent mismatch between the optical classification and X-ray properties of these objects is a challenge for the standard orientation-based AGN unification model. We found that the fraction of objects with detected soft excess is ∼36%. Using a thermal model, we constrained the soft excess mean rest-frame temperature and intrinsic dispersion to kT ∼ 100 eV and σkT ∼ 34 eV. The origin of the soft excess as thermal emission from the accretion disk or Compton scattered disk emission is ruled out on the basis of the temperatures detected and the lack of correlation of the soft excess temperature with the hard X-ray luminosity over more than 2 orders of magnitude in luminosity. Furthermore, the high luminosities of the soft excess rule out an origin in the host galaxy.We acknowledge Chris Done, Bozena Czerny, Gordon Stewart, Pilar Esquej and Ken Pounds for useful comments. We acknowledge the anonymous referee for a careful reading of the manuscript and for comments that improved the paper. S.M., M.W. and J.A.T. acknowledge support from the UK STFC research council. F.J.C. acknowledges financial support for this work from the Spanish Ministerio de Educación y Ciencia under project ESP2006-13608-C02-01. A.C. acknowledges financial support from the Spanish Ministerio de Educación y Ciencia fellowship and also from the MIUR and The Italian Space Agency (ASI) grants PRIN-MUR 2006-02-5203 and No. I/088/06/0. M.K. acknowledges support from the NASA grant NNX08AX50G and NNX07AG02G

Development and Deployment of the OpenMRS-Ebola Electronic Health Record System for an Ebola Treatment Center in Sierra Leone.

BACKGROUND: Stringent infection control requirements at Ebola treatment centers (ETCs), which are specialized facilities for isolating and treating Ebola patients, create substantial challenges for recording and reviewing patient information. During the 2014-2016 West African Ebola epidemic, paper-based data collection systems at ETCs compromised the quality, quantity, and confidentiality of patient data. Electronic health record (EHR) systems have the potential to address such problems, with benefits for patient care, surveillance, and research. However, no suitable software was available for deployment when large-scale ETCs opened as the epidemic escalated in 2014. OBJECTIVE: We present our work on rapidly developing and deploying OpenMRS-Ebola, an EHR system for the Kerry Town ETC in Sierra Leone. We describe our experience, lessons learned, and recommendations for future health emergencies. METHODS: We used the OpenMRS platform and Agile software development approaches to build OpenMRS-Ebola. Key features of our work included daily communications between the development team and ground-based operations team, iterative processes, and phased development and implementation. We made design decisions based on the restrictions of the ETC environment and regular user feedback. To evaluate the system, we conducted predeployment user questionnaires and compared the EHR records with duplicate paper records. RESULTS: We successfully built OpenMRS-Ebola, a modular stand-alone EHR system with a tablet-based application for infectious patient wards and a desktop-based application for noninfectious areas. OpenMRS-Ebola supports patient tracking (registration, bed allocation, and discharge); recording of vital signs and symptoms; medication and intravenous fluid ordering and monitoring; laboratory results; clinician notes; and data export. It displays relevant patient information to clinicians in infectious and noninfectious zones. We implemented phase 1 (patient tracking; drug ordering and monitoring) after 2.5 months of full-time development. OpenMRS-Ebola was used for 112 patient registrations, 569 prescription orders, and 971 medication administration recordings. We were unable to fully implement phases 2 and 3 as the ETC closed because of a decrease in new Ebola cases. The phase 1 evaluation suggested that OpenMRS-Ebola worked well in the context of the rollout, and the user feedback was positive. CONCLUSIONS: To our knowledge, OpenMRS-Ebola is the most comprehensive adaptable clinical EHR built for a low-resource setting health emergency. It is designed to address the main challenges of data collection in highly infectious environments that require robust infection prevention and control measures and it is interoperable with other electronic health systems. Although we built and deployed OpenMRS-Ebola more rapidly than typical software, our work highlights the challenges of having to develop an appropriate system during an emergency rather than being able to rapidly adapt an existing one. Lessons learned from this and previous emergencies should be used to ensure that a set of well-designed, easy-to-use, pretested health software is ready for quick deployment in future

The AOLI low-order non-linear curvature wavefront sensor: a method for high sensitivity wavefront reconstruction

The Adaptive Optics Lucky Imager (AOLI) is a new instrument under development to demonstrate near diffraction limited imaging in the visible on large ground-based telescopes. We present the adaptive optics system being designed for the instrument comprising a large stroke deformable mirror, fixed component non-linear curvature wavefront sensor and photon-counting EMCCD detectors. We describe the optical design of the wavefront sensor where two photoncounting CCDs provide a total of four reference images. Simulations of the optical characteristics of the system are discussed, with their relevance to low and high order AO systems. The development and optimisation of high-speed wavefront reconstruction algorithms are presented. Finally we discuss the results of simulations to demonstrate the sensitivity of the system.Comment: 10 pages. To be published in Proc SPIE 8447: Adaptive Optics Systems II

HES5 silencing is an early and recurrent change in prostate tumourigenesis.

Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86-97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour-normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2'-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.The authors are grateful to study volunteers for their participation and staff at the Welcome Trust Clinical Research Facility, Addenbrooke’s Clinical Research Centre, Cambridge. They also thank the NIHR Cambridge Biomedical Research Centre, the DOH HTA (ProtecT grant), and the NCRI/MRC (ProMPT grant) for help with the bio-repository, The University of Cambridge, Hutchison Whampoa Limited and Cancer Research UK for funding. They are grateful to the CRUK Cambridge Institute Genomics and Bioinformatics Core Facilities. Cross-validation of HES5 methylation includes the use of data generated by the TCGA Research Network.This is the final version of the article. It was originally published in the Endocrine-Related Cancer, April 1, 2015 22 131-144 doi: 10.1530/ERC-14-0454

The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.

The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression).We thank CRUK, The NIHR, The Academy of Medical Sciences(RG:63397) and the National Cancer Research Prostate Cancer: Mechanisms of Progression and Treatment (ProMPT) collaborative (G0500966/75466), Hutchison Whampoa Limited, the Human Research Tissue Bank (Addenbrooke’s Hospital, supported by the NIHR Cambridge BRC), and Cancer Research UK

A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation

Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research