Spatiotemporal epidemiology of rabies at an interface between domestic dogs and wildlife in South Africa

We characterized the spatiotemporal epidemiology of rabies from January 2009 through March 2014 across the interface between a wildlife reserve and communal livestock farming area in South Africa. Brain tissue from 344 animals of 28 different species were tested for lyssavirus antigen. Of these, 146 (42.4%) samples tested positive, of which 141 (96.6%) came from dogs. Brain samples of dogs were more likely to test positive for lyssavirus antigen if they were found and destroyed in the reserve, compared to samples originating from dogs outside the reserve (65.3% vs. 45.5%; odds ratio (OR) = 2.26, 95% confidence interval (CI) = 1.27–4.03), despite rabies surveillance outside the reserve being targeted to dogs that have a higher index of suspicion due to clinical or epidemiological evidence of infection. In the reserve, dogs were more likely to test positive for rabies if they were shot further from villages (OR = 1.42, 95% CI 1.18–1.71) and closer to water points (OR = 0.41, 95% CI 0.21–0.81). Our results provide a basis for refinement of existing surveillance and control programs to mitigate the threat of spillover of rabies to wildlife populations.http://www.nature.com/srepam2019Veterinary Tropical Disease

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

<p><b>Background:</b> Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.</p> <p><b>Methodology/Principal Findings:</b> This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.</p> <p><b>Conclusions/Significance:</b> We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.</p&gt

Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Modeling “psychosis” in vitro by inducing disordered neuronal network activity in cortical brain slices

# The Author(s) 2009. This article is published with open access at Springerlink.com Introduction Dysregulation of neuronal networks has been suggested to underlie the cognitive and perceptual abnor-malities observed schizophrenia. Discussions An in vitro model of psychosis is proposed based on the two different approaches to cause aberrant networ

ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks

An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ∼0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

An uncertainty principle for star formation - II. A new method for characterising the cloud-scale physics of star formation and feedback across cosmic history

The cloud-scale physics of star formation and feedback represent the main uncertainty in galaxy formation studies. Progress is hampered by the limited empirical constraints outside the restricted environment of the Local Group. In particular, the poorly-quantified time evolution of the molecular cloud lifecycle, star formation, and feedback obstructs robust predictions on the scales smaller than the disc scale height that are resolved in modern galaxy formation simulations. We present a new statistical method to derive the evolutionary timeline of molecular clouds and star-forming regions. By quantifying the excess or deficit of the gas-to-stellar flux ratio around peaks of gas or star formation tracer emission, we directly measure the relative rarity of these peaks, which allows us to derive their lifetimes. We present a step-by-step, quantitative description of the method and demonstrate its practical application. The method's accuracy is tested in nearly 300 experiments using simulated galaxy maps, showing that it is capable of constraining the molecular cloud lifetime and feedback time-scale to $<0.1$ dex precision. Access to the evolutionary timeline provides a variety of additional physical quantities, such as the cloud-scale star formation efficiency, the feedback outflow velocity, the mass loading factor, and the feedback energy or momentum coupling efficiencies to the ambient medium. We show that the results are robust for a wide variety of gas and star formation tracers, spatial resolutions, galaxy inclinations, and galaxy sizes. Finally, we demonstrate that our method can be applied out to high redshift ($z\lesssim4$) with a feasible time investment on current large-scale observatories. This is a major shift from previous studies that constrained the physics of star formation and feedback in the immediate vicinity of the Sun

O6-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib

We evaluated the pharmacodynamic effects of the O6-methylguanine-DNA methyltransferase (MGMT) inactivator lomeguatrib (LM) on patients with melanoma in two clinical trials. Patients received temozolomide (TMZ) for 5 days either alone or with LM for 5, 10 or 14 days. Peripheral blood mononuclear cells (PBMCs) were isolated before treatment and during cycle 1. Where available, tumour biopsies were obtained after the last drug dose in cycle 1. Samples were assayed for MGMT activity, total MGMT protein, and O6-methylguanine (O6-meG) and N7-methylguanine levels in DNA. MGMT was completely inactivated in PBMC from patients receiving LM, but detectable in those on TMZ alone. Tumours biopsied on the last day of treatment showed complete inactivation of MGMT but there was recovery of activity in tumours sampled later. Significantly more O6-meG was present in the PBMC DNA of LM/TMZ patients than those on TMZ alone. LM/TMZ leads to greater MGMT inactivation, and higher levels of O6-meG than TMZ alone. Early recovery of MGMT activity in tumours suggested that more protracted dosing with LM is required. Extended dosing of LM completely inactivated PBMC MGMT, and resulted in persistent levels of O6-meG in PBMC DNA during treatment

Unintended Consequences of Conservation Actions: Managing Disease in Complex Ecosystems

Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV) targeted at conserving the African lion (Panthera leo), could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus). Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions