The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal ...physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities.
Here, we provide data supporting an in vivo function for Abeta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies.
Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Artisanal and small-scale gold mining (ASGM) is crucial to the livelihoods of close to 20 million people in over 80 countries, including 4-5 million women, mainly in rural areas with limited ...alternative economic prospects, particularly in developing countries. ASGM is largely informal, which can add to the challenge of addressing negative social and environmental effects including impacts on biodiversity. However, with proper guidance, ASGM can operate in a responsible manner, using cleaner production methods that minimize impacts on human health and the environment. This study presents and analyzes the interactions between ASGM and biodiversity based on new findings from 27 ASGM National Action Plans (NAPs) developed within the framework of Article 7 and Annex C of the Minamata Convention on Mercury, as well as a global literature review of more than 100 publications. In terms of key findings according to the literature reviewed, alongside other human occupation such as agriculture and industrial activities, ASGM also has an impact on the environment and biodiversity. The interrelationship between ASGM and biodiversity, including protected areas, is pervasive at every stage of ASGM operations, from extraction to mine closure, and generates significant impacts on the surrounding ecosystems. These impacts include, in descending order of most reported impacts: deforestation, soil degradation, chemical contamination of aquatic and terrestrial systems, and changes to the turbidity of watercourses. Tropical regions and key species such as amphibians and freshwater fish are among the most affected. Singly or combined, these environmental stressors lead to loss or deterioration of habitat and, by extension, indigenous biodiversity and ecosystem services. In addition, legal, institutional, and regulatory frameworks and related measures, inadequate or non-existent in some cases, may not necessarily support sustainable practices, often resulting in exploited sites abandoned without remediation, reclamation, rehabilitation, or restoration measures. To mitigate such impacts a key recommendation arising from the literature review is to strengthen the integration of the interrelationship between ASGM and biodiversity in the implementation of existing relevant national strategies, including those developed under the NAPs. The global literature review also highlights the importance of a multi-stakeholder, systemic approach combining the use of geospatial analysis, scientific and local knowledge, as well as the adaptation of the relevant frameworks, capacity building, and awareness raising. This approach can inform decision making with a view to developing sustainable initiatives that prevent and reduce the impacts of artisanal and small-scale gold mining on ecosystems, and that preserve biodiversity.
An important provision of the Minamata Convention on Mercury is to monitor and evaluate the effectiveness of the adopted measures and its implementation. Here, we describe for the first time ...currently available biotic mercury (Hg) data on a global scale to improve the understanding of global efforts to reduce the impact of Hg pollution on people and the environment. Data from the peer-reviewed literature were compiled in the Global Biotic Mercury Synthesis (GBMS) database (>550,000 data points). These data provide a foundation for establishing a biomonitoring framework needed to track Hg concentrations in biota globally. We describe Hg exposure in the taxa identified by the Minamata Convention: fish, sea turtles, birds, and marine mammals. Based on the GBMS database, Hg concentrations are presented at relevant geographic scales for continents and oceanic basins. We identify some effective regional templates for monitoring methylmercury (MeHg) availability in the environment, but overall illustrate that there is a general lack of regional biomonitoring initiatives around the world, especially in Africa, Australia, Indo-Pacific, Middle East, and South Atlantic and Pacific Oceans. Temporal trend data for Hg in biota are generally limited. Ecologically sensitive sites (where biota have above average MeHg tissue concentrations) have been identified throughout the world. Efforts to model and quantify ecosystem sensitivity locally, regionally, and globally could help establish effective and efficient biomonitoring programs. We present a framework for a global Hg biomonitoring network that includes a three-step continental and oceanic approach to integrate existing biomonitoring efforts and prioritize filling regional data gaps linked with key Hg sources. We describe a standardized approach that builds on an evidence-based evaluation to assess the Minamata Convention’s progress to reduce the impact of global Hg pollution on people and the environment.
Background
Intensive outpatient programs (IOPs) for trauma‐focused therapy, such as prolonged exposure (PE), have the potential to deliver highly effective treatment, quickly and with minimal ...dropout. Identifying factors that predict maintenance of gains after treatment can help triage individuals who may need additional services.
Methods
Growth mixture modeling (GMM) was used to identify classes of posttraumatic stress disorder (PTSD) and depression symptom trajectories across the year following a 2‐week IOP, delivering daily PE for PTSD for post‐9/11 Veterans. Predictors of trajectories were examined.
Results
Three classes of trajectories best‐fit the data for PTSD and depression symptoms. Two classes made up the majority of the sample (85%) and both maintained significantly reduced PTSD symptoms across the year following therapy. For a minority of the sample (14.6%), PTSD symptoms rebounded after treatment. These individuals were highly likely to be categorized in the persistent depression class.
Conclusions
IOP‐delivered PE is effective, and gains are largely maintained. The minority of patients who do not maintain their gains as robustly are likely to report persistent depressive symptoms in treatment and higher PTSD symptoms on a self‐report measure.
Mercury (Hg) inputs have particularly impacted the northeastern United States due to its proximity to anthropogenic emissions sources and abundant habitats that efficiently convert inorganic Hg into ...methylmercury. Intensive research and monitoring efforts over the past 50 years in New York State, USA, have informed the assessment of the extent and impacts of Hg exposure on fishes and wildlife. By synthesizing Hg data statewide, this study quantified temporal trends of Hg exposure, spatiotemporal patterns of risk, the role that habitat and Hg deposition play in producing spatial patterns of Hg exposure in fish and other wildlife, and the effectiveness of current monitoring approaches in describing Hg trends. Most temporal trends were stable, but we found significant declines in Hg exposure over time in some long-sampled fish. The Adirondack Mountains and Long Island showed the greatest number of aquatic and terrestrial species with elevated Hg concentrations, reflecting an unequal distribution of exposure risk to fauna across the state. Persistent hotspots were detected for aquatic species in central New York and the Adirondack Mountains. Elevated Hg concentrations were associated with open water, forests, and rural, developed habitats for aquatic species, and open water and forested habitats for terrestrial species. Areas of consistently elevated Hg were found in areas driven by atmospheric and local Hg inputs, and habitat played a significant role in translating those inputs into biotic exposure. Continued long-term monitoring will be important in evaluating how these patterns continue to change in the face of changing land cover, climate, and Hg emissions.
Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life ...nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.
Mercury is a ubiquitous pollutant of global concern but the threat of exposure is not homogenously distributed at local, regional, or global scales. The primary route of human exposure to mercury is ...through consumption of aquatic foods, which are culturally and economically important in the wider Caribbean Region, especially for Small Island Developing States (SIDS). We compiled more than 1600 samples of 108 unique species of fish and aquatic invertebrates collected between 2005 and 2023 from eleven countries or territories in the wider Caribbean Region. There was wide variability in total mercury concentrations with 55% of samples below the 0.23 µg/g wet weight (ww) guideline from the U.S. FDA/EPA (
2022
) for 2 or 3 weekly servings and 26% exceeding the 0.46 µg/g ww guideline consistent with adverse effects on human health from continual consumption, particularly for sensitive populations. Significant relationships were found between total mercury concentrations and taxonomic family, sampling country, fish length, and trophic level. The data analyzed here support the need for further sampling with concrete geospatial data to better understand patterns and mechanisms in mercury concentrations and allow for more informed decision making on the consumption of fish and invertebrates from the wider Caribbean Region as well as supporting efforts to evaluate the effectiveness of national, regional, and international mercury policies.
•Latent profile analyses identified three classes of PTSD and depression comorbidity.•Those in the low depression class showed high trauma-related avoidance.•High symptom severity predicted greater ...PTSD reduction but lower remission rates.•LPA class was a stronger predictor of treatment response than MDD diagnosis.
Posttraumatic stress disorder (PTSD) frequently co-occurs with major depressive disorder, and empirically supported PTSD treatments consistently improve depression. However, both diagnoses are heterogeneous and specific patterns of symptom overlap may be related to worse treatment outcome. Two hundred individuals with chronic PTSD participated in a doubly randomized preference trial comparing prolonged exposure and sertraline. Latent Profile Analysis was used to identify classes based on PTSD and depression symptoms prior to starting treatment. A three-class model best fit the data, with a high depression and PTSD severity class (distressed), a moderate depression and low PTSD avoidance class (depressive), and a low depression and high PTSD avoidance class (avoidant). The avoidant class showed the lowest rates of major depressive disorder diagnosis and transdiagnostic vulnerabilities to depression. Patients in the distressed class experienced more robust PTSD treatment response, with no differences between prolonged exposure and sertraline. These findings highlight the role of avoidance in nondepressed PTSD presentations while also demonstrating that co-occurring depression is not contraindicated in evidence-based PTSD treatment.
Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats ...in the Neotropics: a region that supports over half of the world’s species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem’s ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (
n
= 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics.
Highlights
We summarized the largest database on Neotropical bird Hg concentrations to identify major patterns of pollution exposure to terrestrial biodiversity in the tropics.
We detected the highest Hg concentrations in carnivorous bird species, aquatic habitats, and gold mining sites.
We showcase among the highest published Hg concentrations for songbirds (Passeriformes) in the world.
Madre de Dios, Peru, central Belize, and Ayapel, Colombia are biological Hg hotspots, but widespread sampling is necessary throughout the Neotropics.
Inclusive collaboration will excel the field of tropical ecotoxicology by improving the efficiency and comparability of future monitoring efforts.
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