Combining modeling with novel field observations yields new insights into wintertime food limitation of larval fish

Recruitment success of marine fishes is generally considered to be highly dependent on larval growth and survival. In temperate ecosystems, fish larvae are sensitive to food limitation during the low productivity seasons, particularly if water temperatures and concomitant larval metabolic costs increase due to climate change. We combined 7 years of in situ sampling of larval fish, novel observations on zooplankton via automated image analyses, and larval physiological modeling to explore feeding conditions of Atlantic herring larvae (Clupea harengus) in the North Sea. The observed plankton size-structure was close to the theoretical optimum for larval foraging, but not the biomass. Our results for autumn larvae supported Hjort's critical period hypothesis: small first-feeding larvae were predicted to have a high probability of starvation, whereas larvae > 13 mm were able to reach their maximal growth capacity. In winter, the majority of herring larvae of all tested sizes (5–27 cm) experienced food-limitation with over 35% probability of starvation. Sensitivity analysis suggested that young herring larvae improve their growth performance and probability of survival if feed not only on copepods and their life-stages but include other microplankters in their diet. Given projected warming of the North Sea, our model predicts that herring larvae would require 28% (35%) more prey biomass in autumn (winter) to sustain their growth and survival in the future. This finding together with the ongoing low recruitment of North Sea herring underscore the importance of future micro- and mesoplankton monitoring within a scope of wintertime larval fish surveys.publishedVersio

Broad-scale distribution of the winter protozooplankton community in the North Sea.

Protozooplankton (PZP) (here size range: 12–200 μm) are rarely sampled over a broad scale, especially in ecosystem monitoring programs, despite their trophodynamic importance as grazers in the microbial loop and as prey for larger zooplankton and early life stages of fish. In this study we sampled PZP from Dutch, French,German and Norwegian research vessels taking part in the annual ICES coordinated International Bottom Trawl Survey (IBTS) which provides data on fish stock abundances and status for the entire North Sea. The abundance,biomass, composition and distribution of PZP were examined at 39 stations across the North Sea (from 3.2°W to 7.6°E and 50.5 to 59.8°N) in mid-winter (January–February 2014), a period of the year which is under-investigated so far. Twenty four taxa of dinoflagellates and ciliates were identified. Two groups comprised 89% of the total abundance of PZP: Gymnodinium spp. and other athecate dinoflagellates (68%) and Strombidium spp. and other naked ciliates (21%). The biomass of PZP at each station ranged between 0.08 and 2.4 μg C L−1, which is much lower than that reported for spring or summer (≥100 μg C L−1) in the North Sea. Relatively small-sized (< 40 μm) PZP contributed 46% of the total biomass. No significant spatial pattern in the composition of the PZP community was found, although the total abundance of tintinnids was highest in the southern North Sea, an important over-wintering area for marine fish larvae. Using this fish survey (IBTS) as a sampling platform allowed us to obtain a synoptic view of the PZP community over a large area. The present collaborative effort provides an example of how existing monitoring platforms can be augmented in the future to collect relevant data and potential ecological indicators needed to advance the ecosystem-based approach to managing marine systems.Broad-scale distribution of the winter protozooplankton community in the North Sea.publishedVersio

Embracing Nature-based Solutions to promote resilient marine and coastal ecosystems

The world is struggling to limit greenhouse gas emissions and reduce the human footprint on nature. We therefore urgently need to think about how to achieve more with actions to address mounting challenges for human health and wellbeing from biodiversity loss, climate change effects, and unsustainable economic and social development. Nature-based Solutions (NBS) have emerged as a systemic approach and an important component of the response to these challenges. In marine and coastal spaces, NBS can contribute to improved environmental health, climate change mitigation and adaptation, and a more sustainable blue economy, if implemented to a high standard. However, NBS have been largely studied for terrestrial – particularly urban – systems, with limited uptake thus far in marine and coastal areas, despite an abundance of opportunities. Here, we provide explanations for this lag and propose the following three research priorities to advance marine and coastal NBS: (1) Improve understanding of marine and coastal biodiversity-ecosystem services relationships to support NBS better designed for rebuilding system resilience and achieving desired ecological outcomes under climate change; (2) Provide scientific guidance on how and where to implement marine and coastal NBS and better coordinate strategies and projects to facilitate their design, effectiveness, and value through innovative synergistic actions; (3) Develop ways to enhance marine and coastal NBS communication, collaboration, ocean literacy and stewardship to raise awareness, co-create solutions with stakeholders, boost public and policy buy-in, and potentially drive a more sustained investment. Research effort in these three areas will help practitioners, policy-makers and society embrace NBS for managing marine and coastal ecosystems for tangible benefits to people and marine life.The study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement MaCoBioS (contract no 869710), FutureMARES (contract no 869300) and REST-COAST (contract no 101037097).info:eu-repo/semantics/publishedVersio

Phase 1 Outreach Plan- Buffalo, NY ITS4US Deployment Project

693JJ321C000005The Buffalo NY ITS4US Deployment Project seeks to improve mobility to, from, and within the Buffalo Niagara Medical Campus by deploying new and advanced technologies with a focus on addressing existing mobility and accessibility challenges. Examples of the technologies to be deployed are electric and self-driving shuttles, a trip planning app that is customized for accessible travel, intersections that use tactile and mobile technologies to enable travelers with disabilities to navigate intersections, and Smart Infrastructure to support outdoor and indoor wayfinding. The deployment geography includes the 120-acre Medical Campus and surrounding neighborhoods with a focus on three nearby neighborhoods (Fruit Belt, Masten Park, and Allentown) with underserved populations (low income, vision loss, deaf or hard of hearing, physical disabilities (including wheeled mobility device users) and older adults). This document is the Outreach Plan, which identifies the outreach efforts this pilot will perform to promote and ensure stakeholder engagement

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The emergence of colistin-resistant Klebsiella pneumoniae strains from swine in Malaysia

Objective: Colistin is the last line of therapy for infections caused by multidrug-resistant Gram-negative bacteria. The objective of this study was to determine the phenotypic and genotypic characteristics of colistin-resistant Klebsiella pneumoniae (K. pneumoniae) isolated from swine samples in Malaysia. Methods: A total of 46 swine K. pneumoniae strains isolated from 2013–2015 in Malaysia were analysed for the production of extended-spectrum β-lactamases and carbapenemase. The resistance traits and genetic diversity of these strains were characterised by polymerase chain reaction, conjugation, plasmid analysis, and pulsed-field gel electrophoresis. Results: Nineteen of 46 strains were multidrug resistant while 13 were resistant to colistin. The majority of colistin-resistant strains harboured blaTEM gene (92.3%), followed by blaSHV (69.23%), blaCTXM-1 (38.46%), and blaMCR-1 (23.08%). All three colistin-resistant strains had transferable plasmids and the colistin resistance gene blaMCR-1. Genotyping by pulsed-field gel electrophoresis showed high genetic diversity among the K. pneumoniae and that the colistin-resistant K. pneumoniae strains were heterogenous. Conclusion: It is believed that this is the first report of colistin-resistant K. pneumoniae among swine strains associated with mcr-1 plasmid in Malaysia. Due to the emergence of β-lactam, carbapenem and colistin resistance, the use of colistin in animal husbandry and agriculture should be avoided to prevent treatment failure. © 2019 International Society for Chemotherapy of Infection and Cance

Lipidomic Profiling of Autophagosome Membrane by Mass Spectrometry

Autophagy is molecular machinery for “self-eating” in cells. It is a highly conserved process of self-degradation of cellular components in response to extra or intracellular stress and signals such as starvation, growth factor deprivation, and pathogen infection. This self-digestion not only provides nutrients to maintain vital cellular functions during fasting but also can rid the cell of superfluous or damaged organelles, misfolded proteins, and invading micro- organisms. Autophagy is a unique membrane trafficking process whereby newly formed membranes, termed phagophores, engulf parts of the cytoplasm leading to the production of double-membraned autophagosomes that get delivered to lysosomes for degradation. The origin of the autophagosomal membrane and how its formation is initiated remain open questions after more than 50 years of investigation. It is still not well understood how the membranes grow and expand to form the autophagosome. In this project, we are using Liquid Chromatography – Mass Spectrometry (LC-MS) to elucidate lipid composition of autophagosome. HeLa-Difluo™ hLC3 cells containing green fluorescence protein (GFP) fused with autophagy protein LC3B are treated with rapamycin for four hours to stimulate autophagy. During the last two hours of treatment period, Bafilomycin A1 are added to block the fusion of autophagosome and lysosome. Cells are then harvested. Autophagosome are purified by immunoprecipitation using GFG antibody. Lipids are extracted and analyzed by LC-MS. The results of this project will contribute to the complete elucidation of lipid composition of the autophagosome membrane and the role of lipids in autophagy

Role of protozooplankton in the diet of North Sea autumn spawning herring (Clupea harengus) larvae

The role of small prey (< 200 µm) in larval marine fish nutrition is largely understudied. Here, we explore the contribution of protozooplankton (PZP 20–200 µm) to larval fish diets, compared to metazoan microzooplankton (MZP 55–200 µm). More specifically, we tested whether the contribution of PZP increased during the low productivity season and decreased as larvae grow. We used North Sea autumn spawning herring (Clupea harengus) as a case study, as it is a key species with high commercial and ecological importance. In autumn and winter, the potential PZP and MZP prey was dominated by cells < 50 µm (mainly Gymnodiniales, Pronoctiluca pelagica,Tripos spp. and Strombidium spp.), while copepod nauplii and copepodites where more abundant in autumn than in winter. Based on their trophic enrichment (∆15 N), larvae preferentially grazed on small MZP < 50 µm rather than PZP both in autumn and winter. Larvae of different body size (range 8–14 mm standard length) fed at the same trophic level but on different prey (similar δ15N but different δ13C). Growth rates (based on RNA/DNA estimates) were similar in autumn and winter, suggesting that growth was not affected by station-specific differences in the composition of the prey field. Our results not only underscore the important role of MZP on larval herring diets both in autumn and wintertime, but also emphasize the limitations of bulk stable isotope analysis. Given the current low recruitment in North Sea herring, these results provide significant information for future monitoring approaches relevant to stock assessment of this species

Role of protozooplankton in the diet of North Sea autumn spawning herring (Clupea harengus) larvae

The role of small prey (<200 µm) in larval marine fsh nutrition is largely understudied. Here, we explore the contribution of protozooplankton (PZP 20–200 µm) to larval fsh diets, compared to metazoan microzooplankton (MZP 55–200 µm). More specifcally, we tested whether the contribution of PZP increased during the low productivity season and decreased as larvae grow. We used North Sea autumn spawning herring (Clupea harengus) as a case study, as it is a key species with high commercial and ecological importance. In autumn and winter, the potential PZP and MZP prey was dominated by cells<50 µm (mainly Gymnodiniales, Pronoctiluca pelagica, Tripos spp. and Strombidium spp.), while copepod nauplii and copepodites where more abundant in autumn than in winter. Based on their trophic enrichment (∆15 N), larvae preferentially grazed on small MZP<50 µm rather than PZP both in autumn and winter. Larvae of diferent body size (range 8–14 mm standard length) fed at the same trophic level but on diferent prey (similar δ15N but diferent δ13C). Growth rates (based on RNA/ DNA estimates) were similar in autumn and winter, suggesting that growth was not afected by station-specifc diferences in the composition of the prey feld. Our results not only underscore the important role of MZP on larval herring diets both in autumn and wintertime, but also emphasize the limitations of bulk stable isotope analysis. Given the current low recruitment in North Sea herring, these results provide signifcant information for future monitoring approaches relevant to stock assessment of this species