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The large-scale spatial dynamics and population structure of marine top predators are poorly known. We present electronic tag and photographic identification data showing a complex suite of behavioral patterns in white sharks. These include coastal return migrations and the fastest known transoceanic return migration among swimming fauna, which provide direct evidence of a link between widely separated populations in South Africa and Australia. Transoceanic return migration involved a return to the original capture location, dives to depths of 980 meters, and the tolerance of water temperatures as low as 3.4°C. These findings contradict previous ideas that female white sharks do not make transoceanic migrations, and they suggest natal homing behavior.

Heaviside's dolphin (Cephalorhynchus heavisidii) is a coastal delphinid with a limited inshore distribution off the west coast of southern Africa. Knowledge of its habitat usage is an essential precursor to assessing its potential vulnerability to fisheries interactions. Six Heaviside's dolphins (1 male and 5 females) were fitted with satellite-linked transmitters in 2004, and tracked for up to 54 days. The 5 tags fitted to female dolphins transmitted continuously, allowing for analysis of movements at a fine temporal scale. Four dolphins showed an initial avoidance of the capture site by moving over a wider area in the first 2–5 days posttagging than later in the deployment period. All dolphins had used their full home ranges (determined as 100% minimum convex polygons) 5–20 days before tag failure, suggesting measured home ranges were stable at this temporal scale. Home-range estimates using local convex hulls ranged from 301.9 to 1,027.6 km2 (90% isopleths) and 875.9 to 1,989.6 km2 using the 100% isopleths and scaled positively with body size but varied in shape, usage, and number of core-use areas. Although the distance from shore and depth at which individual dolphins moved varied greatly, all dolphins showed a strong onshore–offshore diurnal movement pattern, generally being closest inshore between 0600 h and noon, and farthest offshore between 1500 h and 0500 h. This pattern is assumed to be related to the movements of their principal prey, juvenile shallow-water hake (Merluccius capensis), which migrate into the upper water column at night. Movements inshore may be associated with rest, socializing, and predator avoidance.

Because obesity is associated with many co-morbidities, including diabetes mellitus, this study evaluated the second-meal effect of a commercial prebiotic, inulin-type fructans, and the effects of the prebiotic on faecal microbiota, metabolites and bile acids (BA). Nine overweight beagles were used in a replicated 3×3 Latin square design to test a non-prebiotic control (cellulose) against a low (equivalent to 0·5 % diet) and high dose (equivalent to 1·0 % diet) of prebiotic over 14-d treatments. All dogs were fed the same diet twice daily, with treatments provided orally via gelatin capsules before meals. On days 13 or 14 of each period, fresh faecal samples were collected, dogs were fed at 08.00 hours and then challenged with 1 g/kg body weight of maltodextrin in place of the 16.00 hours meal. Repeated blood samples were analysed for glucose and hormone concentrations to determine postprandial incremental AUC (IAUC) data. Baseline glucose, insulin and active glucagon-like peptide-1 levels were similar between all groups (P>0·10). Glucose and insulin IAUC after glucose challenge appeared lower following the high dose, but did not reach statistical relevance. Prebiotic intervention resulted in an increase in relative abundance of some Firmicutes and a decrease in the relative abundance of some Proteobacteria. Individual and total faecal SCFA were significantly increased (P<0·05) following prebiotic supplementation. Total concentration of excreted faecal BA tended to increase in dogs fed the prebiotic (P=0·06). Our results indicate that higher doses of inulin-type prebiotics may serve as modulators of gut microbiota, metabolites and BA pool in overweight dogs.

It is shown that the formation of amyloid-β oligomers, one of the histopathological signatures of Alzheimer’s disease, can be triggered by small quantities of a specifically truncated and post-translationally modified version of amyloid-β. Hypertoxic amyloid variants Here it is demonstrated that the formation of hypertoxic amyloid-β (Aβ) oligomers can be triggered by small quantities of a specifically truncated and post-translationally modified (pyroglutamylated) version of Aβ, called pEAβ. Previous studies have shown that pE modification of Aβ enhances its aggregation kinetics, toxicity and resistance to degradation, but a mechanistic explanation for these observations was lacking. This study shows that pEAβ causes template-induced misfolding of Aβ 1–42 into small hypertoxic structurally distinct oligomers that propagate through a prion-like mechanism. Tau expression is required for the cytotoxicity of these oligomers, and similar molecules can be isolated from the brains of people with Alzheimer's disease. Extracellular plaques of amyloid-β and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer’s disease. Plaques comprise amyloid-β fibrils that assemble from monomeric and oligomeric intermediates, and are prognostic indicators of Alzheimer’s disease. Despite the importance of plaques to Alzheimer’s disease, oligomers are considered to be the principal toxic forms of amyloid-β 1 , 2 . Interestingly, many adverse responses to amyloid-β, such as cytotoxicity 3 , microtubule loss 4 , impaired memory and learning 5 , and neuritic degeneration 6 , are greatly amplified by tau expression. Amino-terminally truncated, pyroglutamylated (pE) forms of amyloid-β 7 , 8 are strongly associated with Alzheimer’s disease, are more toxic than amyloid-β, residues 1–42 (Aβ 1–42 ) and Aβ 1–40 , and have been proposed as initiators of Alzheimer’s disease pathogenesis 9 , 10 . Here we report a mechanism by which pE-Aβ may trigger Alzheimer’s disease. Aβ 3(pE)–42 co-oligomerizes with excess Aβ 1–42 to form metastable low- n oligomers (LNOs) that are structurally distinct and far more cytotoxic to cultured neurons than comparable LNOs made from Aβ 1–42 alone. Tau is required for cytotoxicity, and LNOs comprising 5% Aβ 3(pE)–42 plus 95% Aβ 1–42 (5% pE-Aβ) seed new cytotoxic LNOs through multiple serial dilutions into Aβ 1–42 monomers in the absence of additional Aβ 3(pE)–42 . LNOs isolated from human Alzheimer’s disease brain contained Aβ 3(pE)–42 , and enhanced Aβ 3(pE)–42 formation in mice triggered neuron loss and gliosis at 3 months, but not in a tau-null background. We conclude that Aβ 3(pE)–42 confers tau-dependent neuronal death and causes template-induced misfolding of Aβ 1–42 into structurally distinct LNOs that propagate by a prion-like mechanism. Our results raise the possibility that Aβ 3(pE)–42 acts similarly at a primary step in Alzheimer’s disease pathogenesis.

The use of left-sided Impella microaxial flow pumps has expanded rapidly for the management of cardiogenic shock, left ventricular unloading and as a bridge to heart transplantation. However, standard life support and resuscitation algorithms are not directly applicable to patients receiving this therapy due to fundamental alterations in circulatory physiology. To address this gap, eleven UK Impella centres and eight national professional societies collaborated to develop a unified national consensus statement on the emergency management of patients with left-sided Impella support. Using a systematic review of the literature and a modified Delphi process guided by the European Society of Cardiology framework for grading recommendations, expert representatives achieved agreement on key priorities and structured actions to be undertaken in the first few minutes of resuscitation.The consensus outlines early recognition of circulatory inadequacy (mean arterial pressure <30 mm Hg or end-tidal CO₂ <2 kPa), prompt activation of multidisciplinary responders, reduction of Impella power to P2 before initiating cardiopulmonary resuscitation and structured division of patient-focused and device-focused teams. Device-specific troubleshooting algorithms are presented for suction, malposition, purge-system failure and mechanical malfunction. This multisociety consensus represents the first national standard for emergency management and resuscitation of patients supported by a left-sided Impella device and is intended to inform structured clinical training and improve patient outcomes through rapid, coordinated and physiologically tailored interventions.

Many children with developmental disabilities are not identified before age 3 years of age, preventing them from being able to fully benefit from early intervention services. Early childhood educators, particularly those in Early Head Start (EHS) programs, are important partners in the early identification of children with developmental delays. Learn the Signs. Act Early. (LTSAE) is a program of the U.S. Centers for Disease Control and Prevention that provides free developmental monitoring resources to increase the early identification of children with developmental delays and disabilities. This paper presents findings from the first evaluation of the use of LTSAE resources in EHS, which was conducted across four states and 11 EHS programs from fall 2018 through spring 2019. Surveys (n = 448) and interviews (n = 39) with EHS management, staff, and parents indicated that LTSAE resources were valued and accepted, and their use in EHS considered feasible. Importantly, families and staff reported the LTSAE materials provided shared language to help them more effectively discuss development. These findings inform EHS and other early education programs that wish to enhance developmental monitoring, screening, and referral.

We have used surface plasmon resonance biosensor technology to monitor the assembly and dynamics of a signal transduction complex which controls chemotaxis in Escherichia coli. A quaternary complex formed which consisted of the response regulator CheY, the histidine protein kinase CheA, a coupling protein CheW and a membrane-bound chemoreceptor Tar. Using various experimental conditions and mutant proteins, we have shown that the complex dissociates under conditions that favour phosphorylation of CheY. Direct physical analysis of interactions among proteins in this signal transduction pathway provides evidence for a previously unrecognized binding interaction between the kinase and its substrate. This interaction may be important for enhancing substrate specificity and preventing 'crosstalk' with other systems. The approach is generally applicable to furthering our understanding of how signalling complexes transduce intracellular messages.

IntroductionThe antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD.Methods and analysisPatients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol–five dimensions–five levels of perceived problems (EQ5D-5L), St. George’s COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale.Ethics and disseminationThe study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals.Trial registration number ISRCTN43245574; Pre-results.

The U.S. Department of Defense (DoD) has established challenging goals to increase energy efficiency and reduce greenhouse gas (GHG) emissions of their installations in all five branches of the armed services with an ultimate goal of net zero energy (NZE) installations. These objectives are similar to those of some U.S. communities and college and university campuses. The Engineer Research and Development Center, Construction Engineering Research Laboratory (ERDCCERL) has developed an NZE installation concept and tool, Net Zero Planner, to support NZE planning for DoD installations (Zhivov et al. 2014a; Case et al. 2013; Swanson et al. 2014). Net Zero Planner allows a streamlined energy planning process resulting in development of a road map to meet or exceed installation energy goals at the lowest life-cycle cost. The criteria for success include meeting or exceeding federal and DoD criteria for site and source energy intensity, meeting energy security requirements, and controlling electrical capacity growth requirements at a lower cost when compared to a base-case scenario using the existing master plan and current facility energy efficiency standards. This paper describes the process and the results of the implementation of the energy master planning concept and the tool at the U.S. Military Academy (USMA) at West Point, which was selected as one of eight pilot net zero installations for energy use.

Promotion permutations have recently been associated to each rectangular standard Young tableau by Gaetz--Pechenik--Pfannerer--Striker--Swanson. Here we relate promotion permutations to the Robinson--Schensted (RS) correspondence. More precisely, we show that taking a pair of standard Young tableaux of the same rectangular shape, stacking them, and computing the middle promotion permutation yields the RS permutation of the pair up to simple twists. Moreover, the full list of promotion permutations in this special case encodes Viennot's geometric shadow line construction. As a consequence, we characterize a subset of the collection of possible promotion permutations in terms of crossing and nesting numbers.