Local- versus broad-scale environmental drivers of continental β-diversity patterns in subterranean spider communities across Europe

Macroecologists seek to identify drivers of community turnover (β-diversity) through broad spatial scales. However, the influence of local habitat features in driving broad-scale β-diversity patterns remains largely untested, owing to the objective challenges of associating local-scale variables to continental-framed datasets. We examined the relative contribution of local- versus broad-scale drivers of continental β-diversity patterns, using a uniquely suited dataset of cave-dwelling spider communities across Europe (35–70° latitude). Generalized dissimilarity modelling showed that geographical distance, mean annual temperature and size of the karst area in which caves occurred drove most of β-diversity, with differential contributions of each factor according to the level of subterranean specialization. Highly specialized communities were mostly influenced by geographical distance, while less specialized communities were mostly driven by mean annual temperature. Conversely, local-scale habitat features turned out to be meaningless predictors of community change, which emphasizes the idea of caves as the human accessible fraction of the extended network of fissures that more properly represents the elective habitat of the subterranean fauna. To the extent that the effect of local features turned to be inconspicuous, caves emerge as experimental model systems in which to study broad biological patterns without the confounding effect of local habitat features

Climbing Fiber Burst Size and Olivary Sub-threshold Oscillations in a Network Setting

The inferior olivary nucleus provides one of the two main inputs to the cerebellum: the so-called climbing fibers. Activation of climbing fibers is generally believed to be related to timing of motor commands and/or motor learning. Climbing fiber spikes lead to large all-or-none action potentials in cerebellar Purkinje cells, overriding any other ongoing activity and silencing these cells for a brief period of time afterwards. Empirical evidence shows that the climbing fiber can transmit a short burst of spikes as a result of an olivary cell somatic spike, potentially increasing the information being transferred to the cerebellum per climbing fiber activation. Previously reported results from in vitro studies suggested that the information encoded in the climbing fiber burst is related to the occurrence of the spike relative to the ongoing sub-threshold membrane potential oscillation of the olivary cell, i.e. that the phase of the oscillation is reflected in the size of the climbing fiber burst. We used a detailed three-compartmental model of an inferior olivary cell to further investigate the possible factors determining the size of the climbing fiber burst. Our findings suggest that the phase-dependency of the burst size is present but limited and that charge flow between soma and dendrite is a major determinant of the climbing fiber burst. From our findings it follows that phenomena such as cell ensemble synchrony can have a big effect on the climbing fiber burst size through dendrodendritic gap-junctional coupling between olivary cells

Oxidants, antioxidants, and respiratory tract lining fluids.

Respiratory tract lining fluids (RTLFs) are a heterogeneous group of substances covering the respiratory tract epithelial cells (RTECs) from nasal mucosa to alveoli. Antioxidant contained in the RTLFs can be expected to provide an initial defense against inhaled environmental toxins. The major antioxidants in RTLF include mucin, uric acid, protein (largely albumin), ascorbic acid, and reduced glutathione (GSH). RTLF antioxidants can be augmented by such processes as transudation/exudation of plasma constituents; RTEC secretory processes, including glandular mucus secretion; and cellular antioxidants derived from lysis of RTECs and of inflammatory cells. The antioxidant composition of RTLFs and their role in modulating normal and pathophysiologic RTEC functions under conditions of oxidative stress are yet to be fully characterized

Life Events, Coping, and Posttraumatic Stress Symptoms among Chinese Adolescents Exposed to 2008 Wenchuan Earthquake, China

PURPOSE: To examine the relationship between negative life events, coping styles, and symptoms of post-traumatic stress disorder (PTSD) among adolescent survivors exposed to 2008 Wenchuan Earthquake, China. METHODS: A survey was conducted in a sample of 2250 adolescent students from two schools in Dujiangyan District, a seriously damaged area, 20 kilometers away from the epicenter, 6 months after the earthquake. Participants completed a self-administered questionnaire including demographics, negative life events, coping styles, and PTSD symptoms. RESULTS: Academic pressure was the strongest predictor of adolescents' PTSD symptoms among all negative life events. Main effects of negative life events, positive coping and negative coping on PTSD symptoms were significant in both younger adolescents and older adolescents, while the moderator effects of two coping styles were found significant only within older adolescents. CONCLUSIONS: Coping may play a role to moderate the relationship between post-earthquake negative life events and PTSD symptom, but the function seems to depend on the age of participants. Psychosocial coping skills training may be important in the prevention and intervention of mental health problems in adolescent survivors of traumatic earthquake

From sleep spindles of natural sleep to spike and wave discharges of typical absence seizures: is the hypothesis still valid?

The temporal coincidence of sleep spindles and spike-and-wave discharges (SWDs) in patients with idiopathic generalized epilepsies, together with the transformation of spindles into SWDs following intramuscular injection of the weak GABAA receptor (GABAAR) antagonist, penicillin, in an experimental model, brought about the view that SWDs may represent ‘perverted’ sleep spindles. Over the last 20 years, this hypothesis has received considerable support, in particular by in vitro studies of thalamic oscillations following pharmacological/genetic manipulations of GABAARs. However, from a critical appraisal of the evidence in absence epilepsy patients and well-established models of absence epilepsy it emerges that SWDs can occur as frequently during wakefulness as during sleep, with their preferential occurrence in either one of these behavioural states often being patient dependent. Moreover, whereas the EEG expression of both SWDs and sleep spindles requires the integrity of the entire cortico-thalamo-cortical network, SWDs initiates in cortex while sleep spindles in thalamus. Furthermore, the hypothesis of a reduction in GABAAR function across the entire cortico-thalamo-cortical network as the basis for the transformation of sleep spindles into SWDs is no longer tenable. In fact, while a decreased GABAAR function may be present in some cortical layers and in the reticular thalamic nucleus, both phasic and tonic GABAAR inhibitions of thalamo-cortical neurons are either unchanged or increased in this epileptic phenotype. In summary, these differences between SWDs and sleep spindles question the view that the EEG hallmark of absence seizures results from a transformation of this EEG oscillation of natural sleep

Chitohexaose Activates Macrophages by Alternate Pathway through TLR4 and Blocks Endotoxemia

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

Basic Science Considerations in Primary Total Hip Replacement Arthroplasty

Total Hip Replacement is one of the most common operations performed in the developed world today. An increasingly ageing population means that the numbers of people undergoing this operation is set to rise. There are a numerous number of prosthesis on the market and it is often difficult to choose between them. It is therefore necessary to have a good understanding of the basic scientific principles in Total Hip Replacement and the evidence base underpinning them. This paper reviews the relevant anatomical and biomechanical principles in THA. It goes on to elaborate on the structural properties of materials used in modern implants and looks at the evidence base for different types of fixation including cemented and uncemented components. Modern bearing surfaces are discussed in addition to the scientific basis of various surface engineering modifications in THA prostheses. The basic science considerations in component alignment and abductor tension are also discussed. A brief discussion on modular and custom designs of THR is also included. This article reviews basic science concepts and the rationale underpinning the use of the femoral and acetabular component in total hip replacement