Impacts of Biodiversity Loss on Ocean Ecosystem Services Worm, Boris; Barbier, Edward B; Beaumont, Nicola ...
Science (American Association for the Advancement of Science),
11/2006, Letnik:
314, Številka:
5800
Journal Article
Recenzirano
Human-dominated marine ecosystems are experiencing accelerating loss of populations and species, with largely unknown consequences. We analyzed local experiments, long-term regional time series, and ...global fisheries data to test how biodiversity loss affects marine ecosystem services across temporal and spatial scales. Overall, rates of resource collapse increased and recovery potential, stability, and water quality decreased exponentially with declining diversity. Restoration of biodiversity, in contrast, increased productivity fourfold and decreased variability by 21%, on average. We conclude that marine biodiversity loss is increasingly impairing the ocean's capacity to provide food, maintain water quality, and recover from perturbations. Yet available data suggest that at this point, these trends are still reversible.
Unlike adult mammals, adult frogs regrow their optic nerve following a crush injury, making Xenopus laevis a compelling model for studying the molecular mechanisms that underlie neuronal ...regeneration. Using Translational Ribosome Affinity Purification (TRAP), a method to isolate ribosome-associated mRNAs from a target cell population, we have generated a transcriptional profile by RNA-Seq for retinal ganglion cells (RGC) during the period of recovery following an optic nerve injury. Based on bioinformatic analysis using the Xenopus laevis 9.1 genome assembly, our results reveal a profound shift in the composition of ribosome-associated mRNAs during the early stages of RGC regeneration. As factors involved in cell signaling are rapidly down-regulated, those involved in protein biosynthesis are up-regulated alongside key initiators of axon development. Using the new genome assembly, we were also able to analyze gene expression profiles of homeologous gene pairs arising from a whole-genome duplication in the Xenopus lineage. Here we see evidence of divergence in regulatory control among a significant proportion of pairs. Our data should provide a valuable resource for identifying genes involved in the regeneration process to target for future functional studies, in both naturally regenerative and non-regenerative vertebrates.
•Generated TRAP expression profiles for retinal ganglion cells in an adult injury model.•RNA-Seq reveals down-regulation in cell signaling and cell-type specific factors after injury.•Injury leads to up-regulation in protein biosynthesis genes and initiators of axon development.•Sequence alignment to new gene models shows evidence for divergent regulation of homeolog pairs.•RNA-Seq data are available through public repository and interactive web application.
Despite being twice as likely to get Alzheimer's disease (AD), African Americans have been grossly underrepresented in AD research. While emerging evidence indicates that African Americans with AD ...have lower cerebrospinal fluid (CSF) levels of Tau compared to Caucasians, other differences in AD CSF biomarkers have not been fully elucidated. Here, we performed unbiased proteomic profiling of CSF from African Americans and Caucasians with and without AD to identify both common and divergent AD CSF biomarkers.
Multiplex tandem mass tag-based mass spectrometry (TMT-MS) quantified 1,840 proteins from 105 control and 98 AD patients of which 100 identified as Caucasian while 103 identified as African American. We used differential protein expression and co-expression approaches to assess how changes in the CSF proteome are related to race and AD. Co-expression network analysis organized the CSF proteome into 14 modules associated with brain cell-types and biological pathways. A targeted mass spectrometry method, selected reaction monitoring (SRM), with heavy labeled internal standards was used to measure a panel of CSF module proteins across a subset of African Americans and Caucasians with or without AD. A receiver operating characteristic (ROC) curve analysis assessed the performance of each protein biomarker in differentiating controls and AD by race.
Consistent with previous findings, the increase of Tau levels in AD was greater in Caucasians than in African Americans by both immunoassay and TMT-MS measurements. CSF modules which included 14-3-3 proteins (YWHAZ and YWHAG) demonstrated equivalent disease-related elevations in both African Americans and Caucasians with AD, whereas other modules demonstrated more profound disease changes within race. Modules enriched with proteins involved with glycolysis and neuronal/cytoskeletal proteins, including Tau, were more increased in Caucasians than in African Americans with AD. In contrast, a module enriched with synaptic proteins including VGF, SCG2, and NPTX2 was significantly lower in African Americans than Caucasians with AD. Following SRM and ROC analysis, VGF, SCG2, and NPTX2 were significantly better at classifying African Americans than Caucasians with AD.
Our findings provide insight into additional protein biomarkers and pathways reflecting underlying brain pathology that are shared or differ by race.
Abstract
Introduction
By 2030, hearing impairment is expected to affect one in four people globally (WHO, 2022) and one in five in the UK (Hearing Link, 2023). Visual impairment is projected to ...impact 2.7 million people in the UK by 2030 (ONS, 2020), rising to 4 million by 2050. The prevalence of hearing and visual impairment (hereafter referred to as sensory impairment (SI)) increases with age and older people with SI often experience substantial challenges with medicine management compared with older people without SI (Alhusein, 2019). This review aimed to identify guidelines and resources for prescribing decisions for older people with sensory impairment (OPwSI).
Methods
Standard Joanna Briggs Institute JBI methodology (Page, 2021) for scoping reviews was used. Electronic databases were searched: MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Qualitative and quantitative studies published between January 2012 and April 2023 were included. Grey literature sources, including Google and Google Scholar, were also searched. Eligible studies focused on prescribing behaviour for OPwSI (aged ≥65 years) in primary care settings. Duplicate independent screening and data extraction was undertaken and critical appraisal completed for all included studies.
Results
A total of 3590 records were identified through database searching and 10 full text articles were retrieved. Grey literature identified a further 61 records. Despite extensive searches, no studies or resources fulfilled the inclusion criteria. Several generic guidelines and resources were identified related to medicines and safe prescribing for older adults in general i.e. without specified SIs.
Conclusions
This review highlights a dearth of guidelines or other resources to support safe and effective prescribing for OPwSI. There is an urgent need to provide bespoke guidance and/or the modification of existing guidelines, to address the additional medicine-related needs of OPwSI.
Several mitochondrial proteins are tumor suppressors. These include
succinate dehydrogenase (
SDH) and
fumarate hydratase, both enzymes of the tricarboxylic acid (TCA) cycle. However, to date, the ...mechanisms by which defects in the TCA cycle contribute to tumor formation have not been elucidated. Here we describe a mitochondrion-to-cytosol signaling pathway that links mitochondrial dysfunction to oncogenic events: succinate, which accumulates as a result of SDH inhibition, inhibits HIF-α prolyl hydroxylases in the cytosol, leading to stabilization and activation of HIF-1α. These results suggest a mechanistic link between
SDH mutations and HIF-1α induction, providing an explanation for the highly vascular tumors that develop in the absence of
VHL mutations.
The profound efficacy, yet associated toxicity of pan-BET inhibitors is well documented. The possibility of an ameliorated safety profile driven by significantly selective (>100-fold) inhibition of a ...subset of the eight bromodomains is enticing, but challenging given the close homology. Herein, we describe the X-ray crystal structure-directed optimization of a novel weak fragment ligand with a pan-second bromodomain (BD2) bias, to potent and highly BD2 selective inhibitors. A template hopping approach, enabled by our parallel research into an orthogonal template (15, GSK046), was the basis for the high selectivity observed. This culminated in two tool molecules, 20 (GSK620) and 56 (GSK549), which showed an anti-inflammatory phenotype in human whole blood, confirming their cellular target engagement. Excellent broad selectivity, developability, and in vivo oral pharmacokinetics characterize these tools, which we hope will be of broad utility to the field of epigenetics research.
Alzheimer's disease (AD) is the most common form of dementia, with cerebrospinal fluid (CSF) β-amyloid (Aβ), total Tau, and phosphorylated Tau (pTau) providing the most sensitive and specific ...biomarkers for diagnosis. However, these diagnostic biomarkers do not reflect the complex changes in AD brain beyond amyloid (A) and Tau (T) pathologies. Here, we report a selected reaction monitoring mass spectrometry (SRM-MS) method with isotopically labeled standards for relative protein quantification in CSF. Biomarker positive (AT+) and negative (AT-) CSF pools were used as quality controls (QCs) to assess assay precision. We detected 62 peptides (51 proteins) with an average coefficient of variation (CV) of ~13% across 30 QCs and 133 controls (cognitively normal, AT-), 127 asymptomatic (cognitively normal, AT+) and 130 symptomatic AD (cognitively impaired, AT+). Proteins that could distinguish AT+ from AT- individuals included SMOC1, GDA, 14-3-3 proteins, and those involved in glycolysis. Proteins that could distinguish cognitive impairment were mainly neuronal proteins (VGF, NPTX2, NPTXR, and SCG2). This demonstrates the utility of SRM-MS to quantify CSF protein biomarkers across stages of AD.
Nitrous oxide emissions from a network of agricultural experiments in Europe were used to explore the relative importance of site and management controls of emissions. At each site, a selection of ...management interventions were compared within replicated experimental designs in plot-based experiments. Arable experiments were conducted at Beano in Italy, El Encin in Spain, Foulum in Denmark, Logården in Sweden, Maulde in Belgium, Paulinenaue in Germany, and Tulloch in the UK. Grassland experiments were conducted at Crichton, Nafferton and Peaknaze in the UK, Gödöllö in Hungary, Rzecin in Poland, Zarnekow in Germany and Theix in France. Nitrous oxide emissions were measured at each site over a period of at least two years using static chambers. Emissions varied widely between sites and as a result of manipulation treatments. Average site emissions (throughout the study period) varied between 0.04 and 21.21 kg N2O-N ha−1 yr−1, with the largest fluxes and variability associated with the grassland sites. Total nitrogen addition was found to be the single most important determinant of emissions, accounting for 15% of the variance (using linear regression) in the data from the arable sites (p < 0.0001), and 77% in the grassland sites. The annual emissions from arable sites were significantly greater than those that would be predicted by IPCC default emission factors. Variability of N2O emissions within sites that occurred as a result of manipulation treatments was greater than that resulting from site-to-site and year-to-year variation, highlighting the importance of management interventions in contributing to greenhouse gas mitigation.
Summary The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens–Johnson syndrome (SJS), toxic ...epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to: ∗ offer an appraisal of all relevant literature up to February 2016, focusing on any key developments. ∗ address important, practical clinical questions relating to the primary guideline objective, i.e. accurate diagnosis and identification of cases and suitable treatment. ∗ provide guideline recommendations. ∗ discuss areas of uncertainty, potential developments and future directions.
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