Large carnivore distribution, conflicts and threats in the east of the Somali region, Ethiopia

Large carnivore distribution in Ethiopia is not well documented; we did 108 interviews and 12 focus group discussions in six districts of the Somali Region to gather basic information. The Region is not listed as resident range for big cats, but our results indicate widespread presence of cheetah, and possible remnants of lion and leopard occurrence. Spotted and striped hyaena, plus many smaller species, are frequently encountered. In contrast to positive attitudes towards wild grazers, all carnivores are persecuted in response to frequent conflict leading to injuries and deaths among people and livestock. Lion and cheetah cubs were regularly captured and trafficked, and this may have contributed to lion declines especially. Cheetah cubs are still regularly caught and we mapped how they are smuggled to Somalia/Somaliland from where they enter the pet trade

Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations.

The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP). Although well documented, the correlation between SCN9A genotypes and clinical phenotypes is still unclear. Here we report three families with novel SCN9A mutations. In a multiaffected dominant family with IEM, we found the heterozygous change L245 V. Electrophysiological characterization showed that this mutation did not affect channel activation but instead resulted in incomplete fast inactivation and a small hyperpolarizing shift in steady-state slow inactivation, characteristics more commonly associated with PEPD. In two compound heterozygous CIP patients, we found mutations that still retained functionality of the channels, with two C-terminal mutations (W1775R and L1831X) exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To our knowledge, these are the first descriptions of mutations with some retained channel function causing CIP. This study emphasizes the complex genotype-phenotype correlations that exist for SCN9A and highlights the C-terminal cytoplasmic region of NaV1.7 as a critical region for channel function, potentially facilitating analgesic drug development studies.J.J.C. and A.M.H. were supported by an MRC Research Career Development fellowship. F.M.G., F.R., and E.C.E. were supported by Wellcome Trust Senior Fellowships WT088357/Z/09/Z and WT084210/Z/07/Z and MRC Grant MC_UU_12012/3. C.G.W. was supported by the Cambridge Biomedical Research Campus.This is the final published version. It first appeared at http://www.jneurosci.org/content/35/20/7674.short

Molecular basis of FAAH-OUT-associated human pain insensitivity

Chronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological dysfunctions that lead to human inherited pain insensitivity disorders. Here we report how the recently discovered brain and dorsal root ganglia-expressed FAAH-OUT long non-coding RNA (lncRNA) gene, which was found from studying a pain-insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system gene FAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme. We demonstrate that the disruption in FAAH-OUT lncRNA transcription leads to DNMT1-dependent DNA methylation within the FAAH promoter. In addition, FAAH-OUT contains a conserved regulatory element, FAAH-AMP, that acts as an enhancer for FAAH expression. Furthermore, using transcriptomic analyses in patient-derived cells we have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed. Given that FAAH is a potential target for the treatment of pain, anxiety, depression and other neurological disorders, this new understanding of the regulatory role of the FAAH-OUT gene provides a platform for the development of future gene and small molecule therapies

Stochastic excitation of acoustic modes in stars

For more than ten years, solar-like oscillations have been detected and frequencies measured for a growing number of stars with various characteristics (e.g. different evolutionary stages, effective temperatures, gravities, metal abundances ...). Excitation of such oscillations is attributed to turbulent convection and takes place in the uppermost part of the convective envelope. Since the pioneering work of Goldreich & Keely (1977), more sophisticated theoretical models of stochastic excitation were developed, which differ from each other both by the way turbulent convection is modeled and by the assumed sources of excitation. We review here these different models and their underlying approximations and assumptions. We emphasize how the computed mode excitation rates crucially depend on the way turbulent convection is described but also on the stratification and the metal abundance of the upper layers of the star. In turn we will show how the seismic measurements collected so far allow us to infer properties of turbulent convection in stars.Comment: Notes associated with a lecture given during the fall school organized by the CNRS and held in St-Flour (France) 20-24 October 2008 ; 39 pages ; 11 figure

A closure model with plumes I. The solar convection

Oscillations of stellar p modes, excited by turbulent convection, are investigated. We take into account the asymmetry of the up and downflows created by turbulent plumes through an adapted closure model. In a companion paper, we apply it to the formalism of excitation of solar p modes developed by Samadi & Goupil 2001. Using results from 3D numerical simulations of the upper most part of the solar convection zone, we show that the two-scale-mass-flux model (TFM) is valid only for quasi-laminar or highly skewed flows (Gryanik & Hartmann 2002). We build a generalized-Two-scale-Mass-Flux Model (GTFM) model which takes into account both the skew introduced by the presence of two flows and the effects of turbulence in each flow. In order to apply the GTFM to the solar case, we introduce the plume dynamics as modelled by Rieutord & Zahn (1995) and construct a Closure Model with Plumes (CMP). When comparing with 3D simulation results, the CMP improves the agreement for the fourth order moments, by approximatively a factor of two compared with the use of the quasi-normal approximation or a skewness computed with the classical TFM. The asymmetry of turbulent convection in the solar case has an important impact on the vertical-velocity fourth-order moment which has to be accounted for by models. The CMP is a significant improvement and is expected to improve the modelling of solar p-mode excitation.Comment: 13 pages, accepted for publication in A&

Resilience from the ground up: how are local resilience perceptions and global frameworks aligned?

Numerous resilience measurement frameworks for climate programmes have emerged over the past decade to operationalise the concept and aggregate results within and between programmes. Proxies of resilience, including subjective measures using perception data, have been proposed to measure resilience, but there is limited evidence on their validity and use for policy and practice. This article draws on research on the Decentralising Climate Funds project of the Building Resilience and Adaptation to Climate Extremes and Disasters programme, which supports communities in Mali and Senegal to improve climate resilience through locally controlled adaptation funds. It explores attributes of resilience from this bottom‐up perspective to assess its predictors and alignment with food security, as a proxy of well‐being. We find different patterns when comparing resilience and the well‐being proxy, illustrating that the interplay between the two is still unclear. Results also point to the importance of contextualising resilience, raising implications for aggregating results