Strong evidences of hadron acceleration in Tycho's Supernova Remnant

Very recent gamma-ray observations of G120.1+1.4 (Tycho's) supernova remnant (SNR) by Fermi-LAT and VERITAS provided new fundamental pieces of information for understanding particle acceleration and non-thermal emission in SNRs. We want to outline a coherent description of Tycho's properties in terms of SNR evolution, shock hydrodynamics and multi-wavelength emission by accounting for particle acceleration at the forward shock via first order Fermi mechanism. We adopt here a quick and reliable semi-analytical approach to non-linear diffusive shock acceleration which includes magnetic field amplification due to resonant streaming instability and the dynamical backreaction on the shock of both cosmic rays (CRs) and self-generated magnetic turbulence. We find that Tycho's forward shock is accelerating protons up to at least 500 TeV, channelling into CRs about the 10 per cent of its kinetic energy. Moreover, the CR-induced streaming instability is consistent with all the observational evidences indicating a very efficient magnetic field amplification (up to ~300 micro Gauss). In such a strong magnetic field the velocity of the Alfv\'en waves scattering CRs in the upstream is expected to be enhanced and to make accelerated particles feel an effective compression factor lower than 4, in turn leading to an energy spectrum steeper than the standard prediction {\propto} E^-2. This latter effect is crucial to explain the GeV-to-TeV gamma-ray spectrum as due to the decay of neutral pions produced in nuclear collisions between accelerated nuclei and the background gas. The self-consistency of such an hadronic scenario, along with the fact that the concurrent leptonic mechanism cannot reproduce both the shape and the normalization of the detected the gamma-ray emission, represents the first clear and direct radiative evidence that hadron acceleration occurs efficiently in young Galactic SNRs.Comment: Minor changes. Accepted for publication in Astronomy & Astrophysic

Effect of lactation stage and concurrent pregnancy on milk composition in the bottlenose dolphin

Although many toothed whales (Cetacea: Odontoceti) lactate for 2–3 years or more, it is not known whether milk composition is affected by lactation stage in any odontocete species. We collected 64 pooled milk samples spanning 1–30 months postpartum from three captive bottlenose dolphins Tursiops truncatus. Milks were assayed for water, fat, crude protein (TN × 6.38) and sugar; gross energy was calculated. Ovulation and pregnancy were determined via monitoring of milk progesterone. Based on analysis of changes in milk composition for each individual dolphin, there were significant increases (P<0.05) in fat (in all three dolphins) and crude protein (in two of three), and a decrease (P<0.05) in water (in two of three) over the course of lactation, but the sugar content did not change. In all three animals, the energy content was positively correlated with month of lactation, but the percentage of energy provided by crude protein declined slightly but significantly (P<0.05). At mid-lactation (7–12 months postpartum, n=17), milk averaged 73.0±1.0% water, 12.8±1.0% fat, 8.9±0.5% crude protein, 1.0±0.1% sugar, 1.76±0.09 kcal g−1 (=7.25 kJ g−1) and 30.3±1.3% protein:energy per cent. This protein:energy per cent was surprisingly high compared with other cetaceans and in relation to the growth rates of calves. Milk progesterone indicated that dolphins ovulated and conceived between 413 and 673 days postpartum, following an increase in milk energy density. The significance of these observed compositional changes to calf nutrition will depend on the amounts of milk produced at different stages of lactation, and how milk composition and yield are influenced by sampling procedure, maternal diet and maternal condition, none of which are known

Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood-brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology

Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection

In the last decades, many regional and country‐wide control programmes for Johne's disease (JD) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were not followed, including the introduction of infected replacement cattle, because tests to identify infected animals were unreliable, and uptake by farmers was not high enough because of a perceived low return on investment. In the absence of a cure or effective commercial vaccines, control of JD is currently primarily based on herd management strategies to avoid infection of cattle and restrict within‐farm and farm‐to‐farm transmission. Although JD control programmes have been implemented in most developed countries, lessons learned from JD prevention and control programmes are underreported. Also, JD control programmes are typically evaluated in a limited number of herds and the duration of the study is less than 5 year, making it difficult to adequately assess the efficacy of control programmes. In this manuscript, we identify the most important gaps in knowledge hampering JD prevention and control programmes, including vaccination and diagnostics. Secondly, we discuss directions that research should take to address those knowledge gaps.http://wileyonlinelibrary.com/journal/tbed2019-05-01hj2018Veterinary Tropical Disease