The structure of gravel-bed flow with intermediate submergence: a laboratory study

The paper reports an experimental study of the flow structure over an immobile gravel bed in open channel at intermediate submergence, with particular focus on the near-bed region. The experiments consisted of velocity measurements using three-component (stereoscopic) Particle Image Velocimetry (PIV) in near-bed horizontal plane and two-component PIV in three vertical planes that covered three distinctly different hydraulic scenarios where the ratio of flow depth to roughness height (i.e., relative submergence) changes from 7.5 to 10.8. Detailed velocity measurements were supplemented with fine-scale bed elevation data obtained with a laser scanner. The data revealed longitudinal low-momentum and high-momentum "strips'' in the time-averaged velocity field, likely induced by secondary currents. This depth-scale pattern was superimposed with particle-scale patches of flow heterogeneity induced by gravel particle protrusions. A similar picture emerged when considering second-order velocity moments. The interaction between the flow field and gravel-bed protrusions is assessed using cross correlations of velocity components and bed elevations in a horizontal plane just above gravel particle crests. The cross correlations suggest that upward and downward fluid motions are mainly associated with upstream-facing and lee sides of particles, respectively. Results also show that the relative submergence affects the turbulence intensity profiles for vertical velocity over the whole flow depth, while only a weak effect, limited to the near-bed region, is noticed for streamwise velocity component. The approximation of mean velocity profiles with a logarithmic formula reveals that log-profile parameters depend on relative submergence, highlighting inapplicability of a conventional "universal'' logarithmic law for gravel-bed flows with intermediate submergence

Vasodilator effect of glucagon: receptorial crosstalk among glucagon, GLP-1, and receptor for glucagon and GLP-1

Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur

Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

The distribution and hydrological significance of rock glaciers in the Nepalese Himalaya

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In the Nepalese Himalaya, there is little information on the number, spatial distribution and morphometric characteristics of rock glaciers, and this information is required if their hydrological contribution is to be understood. Based on freely available fine spatial resolution satellite data accessible through Google Earth, we produced the first comprehensive Nepalese rock glacier inventory, supported through statistical validation and field survey. The inventory includes the location of over 6000 rock glaciers, with a mean specific density of 3.4%. This corresponds to an areal coverage of 1371 km². Our approach subsampled approximately 20% of the total identified rock glacier inventory (n = 1137) and digitised their outlines so that quantitative/qualitative landform attributes could be extracted. Intact landforms (containing ice) accounted for 68% of the subsample, and the remaining were classified as relict (not containing ice). The majority (56%) were found to have a northerly aspect (NE, N, and NW), and landforms situated within north- to west-aspects reside at lower elevations than those with south- to- east aspects. In Nepal, we show that rock glaciers are situated between 3225 to 5675 m a.s.l., with the mean minimum elevation at the front estimated to be 4977±280 m a.s.l. for intact landforms and 4541±346 m a.s.l. for relict landforms. The hydrological significance of rock glaciers in Nepal was then established by statistically upscaling the results from the subsample to estimate that these cryospheric reserves store between 16.72 and 25.08 billion cubic metres of water. This study, for the first time, estimates rock glacier water volume equivalents and evaluates their relative hydrological importance in comparison to ice glaciers. Across the Nepalese Himalaya, rock glacier to ice glacier water volume equivalent is 1:9, and generally increases westwards (e.g., ratio = 1:3, West region). This inventory represents a preliminary step for understanding the spatial distribution and the geomorphic conditions necessary for rock glacier formation in the Himalaya. With continued climatically-driven ice glacier recession, the relative importance of rock glaciers in the Nepalese Himalaya will potentially increase.This work was supported by the Natural Environment Research Council (grant number: 851 NE/L002434/1 to DBJ); the Royal Geographical Society (with IBG) with a Dudley Stamp Memorial Award 852 (awarded to DBJ); the European Union Seventh Framework Programme FP7/2007-2013 (grant number: 603864 853 to SH and RAB [HELIX: High-End cLimate Impacts and eXtremes; www.helixclimate.eu]). The work of RB forms 854 part of the BEIS/Defra Met Office Hadley Centre Climate Programme GA01101.

Distinct patterns of ΔFosB induction in brain by drugs of abuse

The transcription factor ΔFosB accumulates and persists in brain in response to chronic stimulation. This accumulation after chronic exposure to drugs of abuse has been demonstrated previously by Western blot most dramatically in striatal regions, including dorsal striatum (caudate/putamen) and nucleus accumbens. In the present study, we used immunohistochemistry to define with greater anatomical precision the induction of ΔFosB throughout the rodent brain after chronic drug treatment. We also extended previous research involving cocaine, morphine, and nicotine to two additional drugs of abuse, ethanol and Δ9-tetrahydrocannabinol (Δ9-THC, the active ingredient in marijuana). We show here that chronic, but not acute, administration of each of four drugs of abuse, cocaine, morphine, ethanol, and Δ9-THC, robustly induces ΔFosB in nucleus accumbens, although different patterns in the core vs. shell subregions of this nucleus were apparent for the different drugs. The drugs also differed in their degree of ΔFosB induction in dorsal striatum. In addition, all four drugs induced ΔFosB in prefrontal cortex, with the greatest effects observed with cocaine and ethanol, and all of the drugs induced ΔFosB to a small extent in amygdala. Furthermore, all drugs induced ΔFosB in the hippocampus, and, with the exception of ethanol, most of this induction was seen in the dentate. Lower levels of ΔFosB induction were seen in other brain areas in response to a particular drug treatment. These findings provide further evidence that induction of ΔFosB in nucleus accumbens is a common action of virtually all drugs of abuse and that, beyond nucleus accumbens, each drug induces ΔFosB in a region-specific manner in brain

Investigating the distribution and regional occurrence of anthropogenic litter in English Marine Protected Areas using 25 years of citizen-science beach clean data

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordMarine Protected Areas (MPAs) are designated to enable the management of damaging activities within a discrete spatial area, and can be effective at reducing the associated impacts, including habitat loss and over-exploitation. Such sites, however, may be exposed to the potential impacts from broader scale pressures, such as anthropogenic litter, due to its diffuse nature and lack of constraint by legislative and/or political boundaries. Plastic, a large component of litter, is of particular concern, due to increasing evidence of its potential to cause ecological and socio-economic damage. The presence of sensitive marine features may mean that some MPAs are at greater potential risk from the impacts of plastic pollution than some non-protected sites. Understanding the abundance, distribution and composition of litter along coastlines is important for designing and implementing effective management strategies. Gathering such data, however, can be expensive and time37 consuming but litter survey programmes that enlist citizen scientists are often able to resolve many of the logistical or financial constraints. Here, we examine data collected over 25-years (1994 – 2018), by Marine Conservation Society volunteers, for spatial patterns in relation to the English MPA network, with the aim of highlighting key sources of litter and identifying management priority areas. We found that MPAs in southeast (Kent) and southwest (Cornwall and Devon) England have the highest densities of shore-based litter. Plastic is the main material constituent and public littering the most common identifiable source. Items attributed to fishing activities were most prevalent in southwest MPAs and sewage related debris was highest in MPAs near large rivers and estuaries, indicating localised accumulation. When comparing inside and outside of MPAs, we found no difference in litter density, demonstrating the need for wider policy intervention at local, national and international scales to reduce the amount of plastic pollution.Natural EnglandNatural Environment Research Council (NERC)Engineering and Physical Sciences Research Council (EPSRC

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR) = 1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40-64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths