Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats

Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2 weeks) and then either left untrained or step-trained starting 3 weeks after injury for 8 weeks. It was found that sequentially combined therapy improved step consistency and reduced toe dragging and climbing errors, as seen with training and anti-Nogo-A individually. Animals with sequential therapy also adopted a more parallel paw position during bipedal walking and showed greater overall quadrupedal locomotor recovery than individual treatments. Histologically, sequential therapy induced the greatest corticospinal tract sprouting caudally into the lumbar region and increased the number of serotonergic synapses onto lumbar motoneurons. Increased primary afferent sprouting and synapse formation onto lumbar motoneurons observed with anti-Nogo-A antibody were reduced by training. Animals with sequential therapy also showed the highest reduction of lumbar interneuronal activity associated with walking (c-fos expression). No treatment effects for thermal nociception, mechanical allodynia, or lesion volume were observed. The results demonstrate that sequential administration of anti-Nogo-A antibody followed in time with intensive locomotor training leads to superior recovery of lost locomotor functions, which is probably mediated by changes in the interaction between descending sprouting and local segmental networks after SCI

Gut γδ T cells as guardians, disruptors and instigators of cancer

Colorectal cancer is the third most common cancer worldwide with nearly 2 million cases per year. Immune cells and inflammation are a critical component of colorectal cancer progression, and they are used as reliable prognostic indicators of patient outcome. With the growing appreciation for immunology in colorectal cancer, interest is growing on the role γδ T cells have to play, as they represent one of the most prominent immune cell populations in gut tissue. This group of cells consists of both resident populations—γδ intraepithelial lymphocytes (γδ IELs)—and transient populations that each has unique functions. The homeostatic role of these γδ T cell subsets is to maintain barrier integrity and prevent microorganisms from breaching the mucosal layer, which is accomplished through crosstalk with enterocytes and other immune cells. Recent years have seen a surge in discoveries regarding the regulation of γδ IELs in the intestine and the colon with particular new insights into the butyrophilin family. In this review, we discuss the development, specialities, and functions of γδ T cell subsets during cancer progression. We discuss how these cells may be used to predict patient outcome, as well as how to exploit their behavior for cancer immunotherapy

Measurement of the antineutrino neutral-current elastic differential cross section

arXiv:1309.7257v1 [hep-ex

Celiac disease as a potential cause of idiopathic portal hypertension: a case report

<p>Abstract</p> <p>Introduction</p> <p>Idiopathic portal hypertension is a disorder of unknown etiology, clinically characterized by portal hypertension, splenomegaly and anemia secondary to hypersplenism.</p> <p>Case presentation</p> <p>A 54-year-old man was admitted to our hospital for evaluation of malaise, weight loss, abdominal swelling and lower limb edema. His paraclinical tests revealed pancytopenia, large ascites, splenomegaly and esophageal varices consistent with portal hypertension. Duodenal biopsy and serologic findings were compatible with celiac disease. His symptoms improved on a gluten-free diet, but his clinical course was further complicated with ulcerative jejunoileitis, and intestinal T-cell lymphoma.</p> <p>Conclusion</p> <p>It seems that celiac disease, by an increased immune reaction in the splenoportal axis, can result in the development of idiopathic portal hypertension in susceptible affected patients.</p

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects

Mixing of rhyolite, trachyte and basalt magma erupted from a vertically and laterally zoned reservoir, composite flow P1, Gran Canaria

The 14.1 Ma composite welded ignimbrite P1 (45 km3 DRE) on Gran Canaria is compositionally zoned from a felsic lower part to a basaltic top. It is composed of four component magmas mixed in vertically varying proportions: (1) Na-rhyolite (10 km3) zoned from crystal-poor to highly phyric; (2) a continuously zoned, evolved trachyte to sodic trachyandesite magma group (6 km3); (3) a minor fraction of Na-poor trachyandesite (<1 km3); and (4) nearly aphyric basalt (26 km3) zoned from 4.3 to 5.2 wt% MgO. We distinguish three sites and phases of mixing: (a) Mutual mineral inclusions show that mixing between trachytic and rhyolitic magmas occurred during early stages of their intratelluric crystallization, providing evidence for long-term residence in a common reservoir prior to eruption. This first phase of mixing was retarded by increasing viscosity of the rhyolite magma upon massive anorthoclase precipitation and accumulation. (b) All component magmas probably erupted through a ring-fissure from a common upper-crustal reservoir into which the basalt intruded during eruption. The second phase of mixing occurred during simultaneous withdrawal of magmas from the chamber and ascent through the conduit. The overall withdrawal and mixing pattern evolved in response to pre-eruptive chamber zonation and density and viscosity relationships among the magmas. Minor sectorial variations around the caldera reflect both varying configurations at the conduit entrance and unsteady discharge. (c) During each eruptive pulse, fragmentation and particulate transport in the vent and as pyroclastic flows caused additional mixing by reducing the length scale of heterogeneities. Based on considerations of magma density changes during crystallization, magma temperature constraints, and the pattern of withdrawal during eruption, we propose that eruption tapped the P1 magma chamber during a transient state of concentric zonation, which had resulted from destruction of a formerly layered zonation in order to maintain gravitational equilibrium. Our model of magma chamber zonation at the time of eruption envisages a basal high-density Na-poor trachyandesite layer that was overlain by a central mass of highly phyric rhyolite magma mantled by a sheath of vertically zoned trachyte-trachyandesite magma along the chamber walls. A conventional model of vertically stacked horizontal layers cannot account for the deduced density relationships nor for the withdrawal pattern

The hospital microbiome project: Meeting report for the UK science and innovation network UK-USA workshop 'beating the superbugs: Hospital microbiome studies for tackling antimicrobial resistance', October 14th 2013

The UK Science and Innovation Network UK-USA workshop 'Beating the Superbugs: Hospital Microbiome Studies for tackling Antimicrobial Resistance' was held on October 14th 2013 at the UK Department of Health, London. The workshop was designed to promote US-UK collaboration on hospital microbiome studies to add a new facet to our collective understanding of antimicrobial resistance. The assembled researchers debated the importance of the hospital microbial community in transmission of disease and as a reservoir for antimicrobial resistance genes, and discussed methodologies, hypotheses, and priorities. A number of complementary approaches were explored, although the importance of the built environment microbiome in disease transmission was not universally accepted. Current whole genome epidemiological methods are being pioneered in the UK and the benefits of moving to community analysis are not necessarily obvious to the pioneers; however, rapid progress in other areas of microbiology suggest to some researchers that hospital microbiome studies will be exceptionally fruitful even in the short term. Collaborative studies will recombine different strengths to tackle the international problems of antimicrobial resistance and hospital and healthcare associated infections

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure