Superconductivity in Cu_xTiSe_2

Charge density waves (CDWs) are periodic modulations of the conduction electron density in solids. They are collective states that arise from intrinsic instabilities often present in low dimensional electronic systems. The layered dichalcogenides are the most well-studied examples, with TiSe_2 one of the first CDW-bearing materials known. The competition between CDW and superconducting collective electronic states at low temperatures has long been held and explored, and yet no chemical system has been previously reported where finely controlled chemical tuning allows this competition to be studied in detail. Here we report how, upon controlled intercalation of TiSe_2 with Cu to yield Cu_xTiSe_2, the CDW transition is continuously suppressed, and a new superconducting state emerges near x = 0.04, with a maximum T_c of 4.15 K found at x = 0.08. Cu_xTiSe_2 thus provides the first opportunity to study the CDW to Superconductivity transition in detail through an easily-controllable chemical parameter, and will provide new insights into the behavior of correlated electron systems.Comment: Accepted to Nature Physic

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

Diet-induced obesity impairs mitochondrial respiratory responses in tissues that are highly metabolically active, such as the heart. However, less is known about the impact of obesity on the respiratory activity of specific cell types, such as splenic B cells. B cells are of relevance, as they play functional roles in obesity-induced insulin resistance, inflammation, and responses to infection. Here, we tested the hypothesis that high-fat-diet (HFD)-induced obesity could impair the mitochondrial respiration of intact and permeabilized splenic CD19+ B cells isolated from C57BL/6J mice and activated ex vivo with lipopolysaccharide (LPS). High-resolution respirometry was used with intact and permeabilized cells. To reveal potential mechanistic targets by which HFD-induced obesity dysregulates B cell mitochondria, we conducted proteomic analyses and 3D serial block face scanning electron microscopy (SBFEM). High-resolution respirometry revealed that intact LPS-stimulated B cells of obese mice, relative to controls, displayed lower ATP-linked, as well as maximal uncoupled, respiration. To directly investigate mitochondrial function, we used permeabilized LPS-stimulated B cells, which displayed increased H2O2 emission and production with obesity. We also examined oxidative phosphorylation efficiency simultaneously, which revealed that oxygen consumption and ATP production were decreased in LPS-stimulated B cells with obesity relative to controls. Despite minimal changes in total respiratory complex abundance, in LPS-stimulated B cells of obese mice, three of the top ten most downregulated proteins were all accessory subunits of respiratory complex I. SBFEM showed that B cells of obese mice, compared to controls, underwent no change in mitochondrial cristae integrity but displayed increased mitochondrial volume that was linked to bioenergetic function. Collectively, these results establish a proof of concept that HFD-induced obesity dysregulates the mitochondrial bioenergetic metabolism of activated splenic B cells

Examination of a pre-exercise, high energy supplement on exercise performance

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effect of a pre-exercise high energy drink on reaction time and anaerobic power in competitive strength/power athletes. In addition, the effect of the pre-exercise drink on subjective feelings of energy, fatigue, alertness and focus was also explored.</p> <p>Methods</p> <p>Twelve male strength/power athletes (21.1 ± 1.3 y; 179.8 ± 7.1 cm; 88.6 ± 12.1 kg; 17.6 ± 3.3% body fat) underwent two testing sessions administered in a randomized and double-blind fashion. During each session, subjects reported to the Human Performance Laboratory and were provided with either 120 ml of a high energy drink (SUP), commercially marketed as Redline Extreme^®or 120 ml of a placebo (PL) that was similar in taste and appearance but contained no active ingredients. Following consumption of the supplement or placebo subjects rested quietly for 10-minutes prior to completing a survey and commencing exercise. The survey consisted of 4 questions asking each subject to describe their feelings of energy, fatigue, alertness and focus for that moment. Following the completion of the questionnaire subjects performed a 2-minute quickness and reaction test on the Makoto testing device (Makoto USA, Centennial CO) and a 20-second Wingate Anaerobic Power test. Following a 10-minute rest subjects repeated the testing sequence and after a similar rest period a third and final testing sequence was performed. The Makoto testing device consisted of subjects reacting to both a visual and auditory stimulus and striking one out of 30 potential targets on three towers.</p> <p>Results</p> <p>Significant difference in reaction performance was seen between SUP and PL in both average number of targets struck (55.8 ± 7.4 versus 51.9 ± 7.4, respectively) and percent of targets struck (71.9 ± 10.5% versus 66.8 ± 10.9%, respectively). No significant differences between trials were seen in any anaerobic power measure. Subjective feelings of energy (3.5 ± 0.5 versus 3.1 ± 0.5) and focus (3.8 ± 0.5 versus 3.3 ± 0.7) were significantly higher during SUP compared to PL, respectively. In addition, a trend towards an increase in average alertness (p = 0.06) was seen in SUP compared to P.</p> <p>Conclusion</p> <p>Results indicate a significant increase in reaction performance, with no effect on anaerobic power performance. In addition, ingestion of this supplement significantly improves subjective feelings of focus and energy in male strength/power athletes.</p

Embracing ligands. Synthesis, characterisation and the correlation between 59Co NMR and ligand field parameters of Co(III) complexes with a new class of nitrogen-thioether multidentate ligand

The syntheses of the hexadentate ligands 2,2,10,10-tetra(methyleneamine)-4,8-dithiaundecane (PrN(4)S(2)amp), 2,2,11,11-tetra(methyleneamine)-4,9-dithiadodecane (BuN(4)S(2)amp), and 1,2-bis(4,4-methyleneamine)-2-thiapentyl)benzene (XyN(4)S(2)amp) are reported and the complexes [Co(RN(4)S(2)amp)](3+) (R = Pr, Bu, Xy) characterised by single crystal X-ray study. The low-temperature (11 K) absorption spectra have been measured in Nafion films. From the observed positions of both spin-allowed (1)A(1g) --> T-1(1g) and (1)A(1g) --> T-1(2g) and spin forbidden (1)A(1g) --> T-3(1g) and (1)A(1g) --> T-3(2g) bands, octahedral ligand-field parameters (10D(q), B and C) have been determined. DFT calculations suggest that significant interaction between the d-d and CT excitations occurs for the complexes. The calculations offer an explanation for the observed deviations from linearity of the relationship between Co-59 magnetogyric ratio and beta(DeltaE)(-1) (beta = the nephelauxetic ratio; DeltaE the energy of the (1)A(1g) --> T-1(1g) transition) for a series of amine and mixed amine/thioether donor complexes

Genetic approaches to understanding the causes of stuttering

Stuttering is a common but poorly understood speech disorder. Evidence accumulated over the past several decades has indicated that genetic factors are involved, and genetic linkage studies have begun to identify specific chromosomal loci at which causative genes are likely to reside. A detailed investigation of one such region on chromosome 12 has identified mutations in the GNPTAB gene that are associated with stuttering in large families and in the general population. Subsequent studies identified mutations in the functionally related GNPTG and NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway that generates the Mannose 6-phosphate signal, which directs a diverse group of enzymes to their target location in the lysosome of the cell. While mutations in these three genes can be identified in less than 10% of cases of familial stuttering, this knowledge allows a variety of new studies that can help identify the neuropathology that underlies this disorder

The Peripheral Blood Transcriptome Identifies the Presence and Extent of Disease in Idiopathic Pulmonary Fibrosis

<div><h3>Rationale</h3><p>Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.</p> <h3>Methods</h3><p>Gene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted D_LCO and FVC.</p> <h3>Main Measurements and Results</h3><p>At 1% FDR, 1428 genes were differentially-expressed in mild IPF (D_LCO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (D_LCO >35%) compared to controls. When categorized by percent predicted D_LCO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.</p> <h3>Conclusions</h3><p>These results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted D_LCO, but not FVC.</p> </div

Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia.The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage

Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyt

Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing

<p>Abstract</p> <p>Background</p> <p>Sensory input is crucial to the initiation and modulation of swallowing. From a clinical point of view, oropharyngeal sensory deficits have been shown to be an important cause of dysphagia and aspiration in stroke patients. In the present study we therefore investigated effects of functional oropharyngeal disruption on the cortical control of swallowing. We employed whole-head MEG to study cortical activity during self-paced volitional swallowing with and without topical oropharyngeal anesthesia in ten healthy subjects. A simple swallowing screening-test confirmed that anesthesia caused swallowing difficulties with decreased swallowing speed and reduced volume per swallow in all subjects investigated. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of the individual SAM data was performed using a permutation test.</p> <p>Results</p> <p>The analysis of normal swallowing revealed bilateral activation of the mid-lateral primary sensorimotor cortex. Oropharyngeal anesthesia led to a pronounced decrease of both sensory and motor activation.</p> <p>Conclusion</p> <p>Our results suggest that a short-term decrease in oropharyngeal sensory input impedes the cortical control of swallowing. Apart from diminished sensory activity, a reduced activation of the primary motor cortex was found. These findings facilitate our understanding of the pathophysiology of dysphagia.</p

Gastric cancers of Western European and African patients show different patterns of genomic instability

<p>Abstract</p> <p>Background</p> <p>Infection with <it>H. pylori </it>is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of <it>H. pylori </it>infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.</p> <p>Methods</p> <p>DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.</p> <p>Results</p> <p>Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.</p> <p>Conclusions</p> <p>Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.</p