Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity

Plasticity allows organisms to respond to environmental change. Here the authors compare the distribution of cis-regulatory variants in the transcriptomes of Arabidopsis lyrata and A. halleriafter exposure to stress, to trace the role of polygenic selection in the evolution of gene expression plasticity

Polysialylated-neural cell adhesion molecule (PSA-NCAM) in the human trigeminal ganglion and brainstem at prenatal and adult ages

<p>Abstract</p> <p>Background</p> <p>The polysialylated neuronal cell adhesion molecule (PSA-NCAM) is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG) and brainstem neuronal populations at prenatal and adult age.</p> <p>Results</p> <p>Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age, the distribution pattern remains fairly steady, whereas the density of immunoreactive structures and the staining intensity may change and are usually higher in newborn than in adult specimens.</p> <p>Conclusion</p> <p>The results obtained show that, in man, the expression of PSA-NCAM in selective populations of central and peripheral neurons occurs not only during prenatal life, but also in adulthood. They support the concept of an involvement of this molecule in the structural and functional neural plasticity throughout life. In particular, the localization of PSA-NCAM in TG primary sensory neurons likely to be involved in the transmission of protopathic stimuli suggests the possible participation of this molecule in the processing of the relevant sensory neurotransmission.</p

Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group.

The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. in parallel, dementia and cognitive disorders also represent major healthcare and social priorities. although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. an international Consensus Group on “Cognitive Frailty” was organized by the international academy on nutrition and aging (i.a.n.a) and the international association of Gerontology and Geriatrics (i.a.G.G) on april 16th, 2013 in toulouse (France). the present report describes the results of the Consensus Group and provides the first definition of a “Cognitive Frailty” condition in older adults. specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. the consensus panel proposed the identification of the so-called “cognitive frailty” as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. in particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (Cdr=0.5); and 2) exclusion of concurrent ad dementia or other dementias. under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. a potential for reversibility may also characterize this entity. a psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors

Role of Pleiotropy in the Evolution of a Cryptic Developmental Variation in Caenorhabditis elegans

Using vulval phenotypes in Caenorhabditis elegans, the authors show that cryptic genetic variation can evolve through selection for pleiotropic effects that alter fitness, and identify a cryptic variant that has conferred enhanced fitness on domesticated worms under laboratory conditions

Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty

Spontaneously opening GABA receptors play a significant role in neuronal signal filtering and integration

Acknowledgements This work was supported by The Rosetrees Trust Research Grant A1066, RS MacDonald Seedcorn Award and Wellcome Trust—UoE ISSF Award to S.S. The authors thank Prof. David Wyllie (University of Edinburgh) and Prof. Dmitri Rusakov (UCL) for their valuable suggestions on paper preparation.Peer reviewedPublisher PD

Hidden variation mapped.

International audienc

Concept Study for a Mach 6 Transport Aircraft

A conceptual study is here presented and discusscd on the possibility to transport 200 passengers over a distance of about 7000km in a nominal point-to-point mission through the Atlantic (either London-New York or London-Rio) at a cruise Mach number of 6 and an altitude abont 30km. The aim of the study is not to design a specific airplane but to explore today's state of the art technology limits to realize such kind of concept, i.e. to identify if such a mission could succeed today. Because of the challenge the mission poses, its is being optimised with the major disciplines involved by means of Multi-Disciplinary Optimisation (MDO) tools as a way to realize an optimum integrated airframe/propulsion aircraft. The environmental impact is being analysed in terms of the resulting sonic boom. No experimental data but CFD results by means of independent assessments has been generated. The study indicates that today the available technology provides with sufficient maturity to accomplish with the mission in areas like aerodynamic and thermal resistance materials but in others like sonic boom mitigation it is required a deeper insight in the physics. Finally while the present investigation clear identify that complex designs involving large amount of variables from different disciplines could be only possible via MDO/MDA strategies, today such processes still suffer on lack of robustness of the involved tools

Walking with hominins: from the reconstruction of a plausible anatomical model to gait energetics in Neandertals. Methodological aspects

International audienc

Modélisation du comportement hydromécanique d’un joint rocheux sous contrainte normale

Cet article présente une modélisation du comportement normal, hydromécanique, d’un joint rocheux. Souvent, un tel comportement est décrit par des relations empiriques permettant de reproduire la non-linéarité de la courbe d’écrasement (l’effet d’hystérésis observé pendant la réourverture du joint est rarement modélisé). Le modèle que nous exposons ici est une approche physique du processus d’écrasement. La rugosité du joint est prise en compte par un modèle géométrique composé d’un ensemble de plots de hauteurs et surfaces différentes qui se mettent successivement en contact avec l’augmentation de la contrainte normale. La non-réversibilité à la réouverture est obtenue en prenant un comportement élastoplastique avec écrouissage cinématique pour le plot. Moyennant l’identification de quelques paramètres par méthode inverse, il est possible avec ce modèle de reproduire avec une bonne corrélation le comportement de joints de roches de natures différentes (granité ; marbre...). Le modèle permet de trouver la surface en contact des différents plots et donc en cas de pression de liquide de définir une notion du type contrainte effective. On reproduit dans ce cas assez fidèlement le comportement d’une fracture sous contrainte normale et pression interne. Cette approche permet de calculer l’ouverture moyenne du joint, localement en fonction de la contrainte et de la pression. A partir de cette ouverture et de l’utilisation d’une loi classique d’écoulement - la loi cubique - il est possible de modéliser le comportement hydraulique du joint et d’y évaluer la distribution des pressions. De nouveau la correspondance entre la simulation et les résultats expérimentaux est bonne