Epidemiology and fitness effects of wood mouse herpesvirus in a natural host population

Rodent gammaherpesviruses have become important models for understanding human herpesvirus diseases. In particular, interactions between murid herpesvirus 4 and Mus musculus (a non-natural host species) have been extensively studied under controlled laboratory conditions. However, several fundamental aspects of murine gammaherpesvirus biology are not well understood, including how these viruses are transmitted from host to host, and their impacts on host fitness under natural conditions. Here, we investigate the epidemiology of a gammaherpesvirus in free-living wood mice (Apodemus sylvaticus) and bank voles (Myodes glareolus) in a 2-year longitudinal study. Wood mouse herpesvirus (WMHV) was the only herpesvirus detected and occurred frequently in wood mice and also less commonly in bank voles. Strikingly, WMHV infection probability was highest in reproductively active, heavy male mice. Infection risk also showed a repeatable seasonal pattern, peaking in spring and declining through the summer. We show that this seasonal decline can be at least partly attributed to reduced recapture of WMHV-infected adults. These results suggest that male reproductive behaviours could provide an important natural route of transmission for these viruses. They also suggest that gammaherpesvirus infection may have significant detrimental effects in wild hosts, questioning the view that these viruses have limited impacts in natural, co-evolved host species

Quantifying air quality co-benefits to industrial decarbonization: the local Air Emissions Tracking Atlas

IntroductionMany decarbonization technologies have the added co-benefit of reducing short-lived climate pollutants, such as particulate matter (PM), nitrogen oxides (NOx), and sulfur dioxide (SO2), creating a unique opportunity for identifying strategies that promote both climate change solutions and opportunities for air quality improvement. However, stakeholders and decision-makers may struggle to quantify how these co-benefits will impact public health for the communities most affected by industrial air pollution.MethodsTo address this problem, the LOCal Air Emissions Tracking Atlas (LOCAETA) fills a data availability and analysis gap by providing estimated air quality benefits from industrial decarbonization options, such as carbon capture and storage (CCS). These co-benefits are calculated using an algorithm that connects disparate datasets that separately report greenhouse gas emissions and other pollutants at U.S. industrial facilities.ResultsVersion 1.0 of LOCAETA displays the estimated primary PM2.5 emission reduction co-benefits from additional pretreatment equipment for CCS on industrial and power facilities across the state of Louisiana, as well as the potential for VOC and NH3 generation. The emission reductions are presented in the tool alongside facility pollutant emissions information and relevant air quality, environmental, demographic, and public health datasets, such as air toxics cancer risk, satellite and in situ pollutant measurements, and population vulnerability metrics.DiscussionLOCAETA enables regulators, policymakers, environmental justice communities, and industrial and commercial users to compare and contrast quantifiable public health benefits due to air quality impacts from various climate change mitigation strategies using a free and publicly-available tool. Additional pollutant reductions can be calculated using the same methodology and will be available in future versions of the tool

Endothelin receptor antagonism does not prevent the development of in vivo glyceryl trinitrate tolerance in the rat

ABSTRACT There is evidence that increased endothelial production of endothelin-1 (ET-1) may contribute to glyceryl trinitrate (GTN) tolerance. We used the competitive ET A receptor antagonist ZD2574 to determine whether chronic ET A receptor blockade affected the biochemical and functional responses to GTN during the development of GTN tolerance in vivo. Tolerance induced using transdermal GTN patches resulted in a 5.3 Ϯ 1.2-fold increase in the EC 50 value for GTN relaxation in isolated aorta from GTN-tolerant rats. Coadministration of ZD2574 (100 mg kg Ϫ1 t.i.d. for 3 days) during tolerance induction had no effect on GTN-induced relaxation. This dose of ZD2574 markedly blunted the pressor response to ET-1, indicating effective blockade of ET A receptors, and also abolished the initial transient depressor response to ET-1, indicating that blockade of endothelial ET B receptors also occurred using this dosage regimen for ZD2574. Consistent with the relaxation data, coadministration of ZD2574 had no effect on the decrease in GTNinduced cGMP accumulation or on the decrease in GTN biotransformation that occurred in aortae from GTN-tolerant animals. Radioimmunoassay data indicated that the GTN tolerance induction protocol caused a 2.3 Ϯ 0.4-fold and a 2.2 Ϯ 0.5-fold increase in total tissue ET-1 levels in tolerant aorta and vena cava, respectively. These data suggest that chronic inhibition of ET receptors by ZD2574 was not sufficient to prevent or diminish the tolerance-inducing effects of GTN, and that the increase in ET-1 levels observed in tolerant tissues may occur as a consequence of the vascular changes that occur during chronic GTN exposure

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians

Scientific response to a cluster of shark bites

1. Shark bites are of high public concern globally. Information on shark occurrence and behaviour, and of the effects of human behaviours, can help understand the drivers of shark-human interactions. In Australia, a number of shark bite clusters occurred over the last decade. One of these took place in Cid Harbour the Whitsundays, Queensland, a region for which little was known about the shark community. Here, we describe and evaluate the research in response to that shark bite cluster. 2. Fishing methods, acoustic and satellite tracking, and baited remote underwater video cameras (BRUVs) were used to identify the shark species using Cid Harbour, estimate relative abundance, and describe habitat use and residency. Side-scan sonar and BRUVs were also used to assess prey availability. Recreational users were surveyed to understand human behaviour and their awareness and perceptions of ‘Shark Smart’ behaviours. This allowed shark occurrence and behaviour to be interpreted in the context of human behaviours in the Harbour. 3. Eleven shark species were identified. Relative abundance was not unusually high, and residency in Cid Harbour was typically low. For example, 79% of acoustically tagged sharks visited the harbour on <10% days at liberty. Shark prey was available year-round. Notably, anchored boats regularly conduct activities that can attract sharks (dumping food scraps, provisioning and cleaning fish). 4. Alone, the methods used in this study had variable success, but combined they provided a large amount of complementary information. Including a social science component in the research response to the shark bite incidents allowed for a more holistic understanding of the Cid Harbour bite incidents. 5. This study did not identify anything unusual about the shark community that could have contributed to the Cid Harbour shark bite cluster. However, the three incidents involved people bitten almost instantly after entering the water, which is unusual and suggests that feeding/attracting sharks to boats could have been a contributor and also that any species capable of biting humans could have been responsible. 6. The eradication of activities that attract sharks to areas where people enter the water may reduce shark bite risk

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data