White sharks exploit the sun during predatory approaches

There is no conclusive evidence of any nonhuman animal using the sun as part of its predation strategy. Here, we show that the world\u27s largest predatory fish-the white shark (Carcharodon carcharias)-exploits the sun when approaching baits by positioning the sun directly behind them. On sunny days, sharks reversed their direction of approach along an east-west axis from morning to afternoon but had uniformly distributed approach directions during overcast conditions. These results show that white sharks have sufficient behavioral flexibility to exploit fluctuating environmental features when predating. This sun-tracking predation strategy has a number of potential functional roles, including improvement of prey detection, avoidance of retinal overstimulation, and predator concealment

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial

Aim: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. Materials and Methods: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non‐fatal myocardial infarction, non‐fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid‐lowering medication, diabetes duration, atrial fibrillation, high‐density cholesterol, total cholesterol, HbA1c and treatment allocation (once‐weekly exenatide or placebo). Results: Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was −0.68 ± 1.67 and −1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5‐year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1‐SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. Conclusions: eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group

Satellite derived offshore migratory movements of southern right whales (Eubalaena australis) from Australian and New Zealand wintering grounds

Funding: Australian Marine Mammal Center Grant 13/48 AIM, SDG, DH, AL http://www.marinemammals.gov.au/ The Australian Marine Mammal Center was involved in study design and anlaysis through the involvement in the project by AMMC staff, Dr Mike Double and Dr Virgina Andrews-Goff Princess Melikoff Trust Marine Mammal Conservation Program KC New Zealand Department of Conservation SC.Southern right whales (Eubalaena australis) migrate between Austral-winter calving and socialising grounds to offshore mid- to high latitude Austral-summer feeding grounds. In Australasia, winter calving grounds used by southern right whales extend from Western Australia across southern Australia to the New Zealand sub-Antarctic Islands. During the Austral-summer these whales are thought to migrate away from coastal waters to feed, but the location of these feeding grounds is only inferred from historical whaling data. We present new information on the satellite derived offshore migratory movements of six southern right whales from Australasian wintering grounds. Two whales were tagged at the Auckland Islands, New Zealand, and the remaining four at Australian wintering grounds, one at Pirates Bay, Tasmania, and three at Head of Bight, South Australia. The six whales were tracked for an average of 78.5 days (range: 29 to 150) with average individual distance of 38 km per day (range: 20 to 61 km). The length of individually derived tracks ranged from 645–6,381 km. Three likely foraging grounds were identified: south-west Western Australia, the Subtropical Front, and Antarctic waters, with the Subtropical Front appearing to be a feeding ground for both New Zealand and Australian southern right whales. In contrast, the individual tagged in Tasmania, from a sub-population that is not showing evidence of post-whaling recovery, displayed a distinct movement pattern to much higher latitude waters, potentially reflecting a different foraging strategy. Variable population growth rates between wintering grounds in Australasia could reflect fidelity to different quality feeding grounds. Unlike some species of baleen whale populations that show movement along migratory corridors, the new satellite tracking data presented here indicate variability in the migratory pathways taken by southern right whales from Australia and New Zealand, as well as differences in potential Austral summer foraging grounds.Publisher PDFPeer reviewe

The auxin-regulated CrRLK1L kinase ERULUS controls cell wall composition during root hair tip growth

Root hairs facilitate a plant’s ability to acquire soil anchorage and nutrients. Root hair growth is regulated by the plant hormone auxin and dependent on localized synthesis, secretion and modification of the root hair tip cell wall. However, the exact well wall regulators in root hairs controlled by auxin have yet to be determined. In this study, we describe the characterization of ERULUS (ERU), an auxin-induced Arabidopsis receptor-like kinase whose expression is directly regulated by ARF7 and ARF19 transcription factors. ERU belongs to the Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) subfamily of putative cell wall sensor proteins. Imaging of a fluorescent fusion protein revealed that ERU is localized to the apical root hair plasma membrane. ERU regulates cell wall composition in root hairs and modulates pectin dynamics through negative control of pectin methylesterase (PME) activity. Mutant eru (-/-) root hairs accumulate de-esterified homogalacturonan and exhibit aberrant pectin Ca²⁺ binding site oscillations and increased PME activity. Up to 80% of the eru root hair phenotype is rescued by pharmacological supplementation with a PME inhibiting catechin extract. ERU transcription is altered in specific cell wall-related root hair mutants, suggesting it is a target for feedback regulation. Loss of ERU alters the phosphorylation status of FERONIA and H⁺-ATPases 1/2, regulators of apoplastic pH. Furthermore, H⁺-ATPases 1/2 and ERU are differentially phosphorylated in response to auxin. We conclude that ERULUS is a key auxin-controlled regulator of cell wall composition and pectin dynamics during root hair tip growth

Epidemiology of Extended-Spectrum beta-Lactamase-Producing E-coli and Vancomycin-Resistant Enterococci in the Northern Dutch-German Cross-Border Region

Objectives: To reveal the prevalence and epidemiology of extended-spectrum β-lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern Dutch–German border region.Methods: A point-prevalence study on ESBL/pAmpC/CP producing Enterobacteriaceae and VRE was carried out in hospitalized patients in the Northern Netherlands (n = 445, 2012–2013) and Germany (n = 242, 2012). Healthy individuals from the Dutch community (n = 400, 2010–2012) were also screened. In addition, a genome-wide gene-by-gene approach was applied to study the epidemiology of ESBL-Escherichia coli and VRE.Results: A total of 34 isolates from 27 patients (6.1%) admitted to Dutch hospitals were ESBL/pAmpC positive and 29 ESBL-E. coli, three pAmpC-E. coli, one ESBL-Enterobacter cloacae, and one pAmpC-Proteus mirabilis were found. In the German hospital, 18 isolates (16 E. coli and 2 Klebsiella pneumoniae) from 17 patients (7.7%) were ESBL positive. In isolates from the hospitalized patients CTX-M-15 was the most frequently detected ESBL-gene. In the Dutch community, 11 individuals (2.75%) were ESBL/pAmpC positive: 10 ESBL-E. coli (CTX-M-1 being the most prevalent gene) and one pAmpC E. coli. Six Dutch (1.3%) and four German (3.9%) hospitalized patients were colonized with VRE. Genetic relatedness by core genome multi-locus sequence typing (cgMLST) was found between two ESBL-E. coli isolates from Dutch and German cross-border hospitals and between VRE isolates from different hospitals within the same region.Conclusion: The prevalence of ESBL/pAmpC-Enterobacteriaceae was similar in hospitalized patients across the Dutch–German border region, whereas VRE prevalence was slightly higher on the German side. The overall prevalence of the studied pathogens was lower in the community than in hospitals in the Northern Netherlands. Cross-border transmission of ESBL-E. coli and VRE seems unlikely based on cgMLST analysis, however continuous monitoring is necessary to control their spread and stay informed about their epidemiology

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe

Aims: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe. Methods and results: SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. Conclusion: SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe

Partial identification, synthesis and immunolocalization of locustamyoinhibin, the 3rd myoinhibiting neuropeptide isolated from Locusta migratoria

A blocked neuropeptide that suppresses the motility of the cockroach hindgut has been isolated from an extract of 9000 brain-corpora cardiaca-corpora allata-suboesophageal ganglion complexes of Locusta migratoria. Biological activity was monitored during HPLC purification by observing the myoinhibiting activity of column fractions on the isolated hindgut of Leucophaea maderae. Due to the low amount of material left after deblocking, this myoinhibiting peptide - designated as locustamyoinhibin or Lom-MIH - could only be partially sequenced: pGlu-X-Tyr-X'-Lys-Gln-Ser-Ala-Phe-Asn-Ala-Val-Ser-NH2. Nevertheless, the carboxy-terminal nonamer sequence (Lom-MIH(5-13)) was synthesized and also displayed myoinhibiting activity, indicating that the biologically active core lies in the carboxy-terminal sequence. Lom-MIH shows no sequence similarities with other peptides from vertebrate or invertebrate sources and is the third myoinhibiting peptide identified in Locusta migratoria. A polyclonal antiserum was raised against Lom-MIH(5-13) and used to investigate the distribution of immunoreactive peptide in the central nervous system and its associated neurohaemal structures. Two groups of neurons with somata in the optic lobes show locustamyoinhibin (Lom-MIH)-like immunoreactivity. These groups have somata at the dorsal and ventral edge of the lamina ganglionaris. The neurons have dense ramifications in the lamina, with processes extending into the first optic chiasma and into the accessory medulla. Four cell bodies were detected in the protocerebrum, and two cells were found at the externo-lateral edge of the tritocerebrum. No immunoreactive perikarya could be observed in the suboesophageal ganglion nor in the ganglia of the ventral nerve cord. Neither the corpora cardiaca nor the neurohaemal organs of the ventral nerve cord showed immunolabelling. Therefore, our findings provide anatomical evidence for a central neurotransmitter role of Lom-MIH.status: publishe