Direct observation of delithiation as the origin of analog memristance in LixNbO2

The discovery of analog LixNbO2 memristors revealed a promising new memristive mechanism wherein the diffusion of Li+ rather than O2- ions enables precise control of the resistive states. However, directly correlating lithium concentration with changes to the electronic structure in active layers remains a challenge and is required to truly understand the underlying physics. Chemically delithiated single crystals of LiNbO2 present a model system for correlating lithium variation with spectroscopic signatures from operando soft x-ray spectroscopy studies of device active layers. Using electronic structure modeling of the x-ray spectroscopy of LixNbO2 single crystals, we demonstrate that the intrinsic memristive behavior in LixNbO2 active layers results from field-induced degenerate p-type doping. We show that electrical operation of LixNbO2-based memristors is viable even at marginal Li deficiency and that the analog memristive switching occurs well before the system is fully metallic. This study serves as a benchmark for material synthesis and characterization of future LixNbO2-based memristor devices and suggests that valence change switching is a scalable alternative that circumvents the electroforming typically required for filamentary-based memristors

The stress of starvation: glucocorticoid restraint of beta cell development

Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta cell mass and that even at physiological levels they restrain fetal beta cell development in utero. There are emerging clues that this occurs downstream of endocrine commitment by neurogenin 3 but prior to terminal beta cell differentiation. Deciphering the precise mechanism will be important as it might unveil new pathways by which to manipulate beta cell mass that could be exploited as novel therapies for patients with diabetes

Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

<p>Abstract</p> <p>Background</p> <p>Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA). Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2), the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3), the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B), as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5) in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7^thday for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes.</p> <p>Results</p> <p>The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions.</p> <p>Conclusion</p> <p>Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.</p

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons(1,2). Several groups have attributed this apparent plasticity to 'transdifferentiation'(3-5). Others, however, have suggested that cell fusion could explain these results(6-9). Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62789/1/nature02069.pd

Transepithelial Transport and Enzymatic Detoxification of Gluten in Gluten-Sensitive Rhesus Macaques

In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness

Evaluation of groundwater quality and its suitability for drinking and agricultural use in Thanjavur city, Tamil Nadu, India

As groundwater is a vital source of water for domestic and agricultural activities in Thanjavur city due to lack of surface water resources, groundwater quality and its suitability for drinking and agricultural usage were evaluated. In this study, 102 groundwater samples were collected from dug wells and bore wells during March 2008 and analyzed for pH, electrical conductivity, temperature, major ions, and nitrate. Results suggest that, in 90% of groundwater samples, sodium and chloride are predominant cation and anion, respectively, and NaCl and CaMgCl are major water types in the study area. The groundwater quality in the study site is impaired by surface contamination sources, mineral dissolution, ion exchange, and evaporation. Nitrate, chloride, and sulfate concentrations strongly express the impact of surface contamination sources such as agricultural and domestic activities, on groundwater quality, and 13% of samples have elevated nitrate content (>45 mg/l as NO3). PHREEQC code and Gibbs plots were employed to evaluate the contribution of mineral dissolution and suggest that mineral dissolution, especially carbonate minerals, regulates water chemistry.Groundwater suitability for drinking usage was evaluated by the World Health Organization and Indian standards and suggests that 34% of samples are not suitable for drinking. Integrated groundwater suitability map for drinking purposes was created using drinking water standards based on a concept that if the groundwater sample exceeds any one of the standards, it is not suitable for drinking. This map illustrates that wells in zones 1, 2, 3, and 4 are not fit for drinking purpose. Likewise, irrigational suitability of groundwater in the study region was evaluated, and results suggest that 20% samples are not fit for irrigation. Groundwater suitability map for irrigation was also produced based on salinity and sodium hazards and denotes that wells mostly situated in zones 2 and 3 are not suitable for irrigation. Both integrated suitability maps for drinking and irrigation usage provide overall scenario about the groundwater quality in the study area. Finally, the study concluded that groundwater quality is impaired by man-made activities, and proper management plan is necessary to protect valuable groundwater resources inThanjavur city

A school-based resilience intervention to decrease tobacco, alcohol and marijuana use in high school students

<p>Abstract</p> <p>Background</p> <p>Despite schools theoretically being an ideal setting for accessing adolescents and preventing initiation of substance use, there is limited evidence of effective interventions in this setting. Resilience theory provides one approach to achieving such an outcome through improving adolescent mental well-being and resilience. A study was undertaken to examine the potential effectiveness of such an intervention approach in improving adolescent resilience and protective factor scores; and reducing the prevalence of adolescent tobacco, alcohol and marijuana use in three high schools.</p> <p>Methods</p> <p>A non-controlled before and after study was undertaken. Data regarding student resilience and protective factors, and measures of tobacco, alcohol and marijuana use were collected from grade 7 to 10 students at baseline (n = 1449) and one year following a three year intervention (n = 1205).</p> <p>Results</p> <p>Significantly higher resilience and protective factors scores, and significantly lower prevalence of substance use were evident at follow up.</p> <p>Conclusions</p> <p>The results suggest that the intervention has the potential to increase resilience and protective factors, and to decrease the use of tobacco, alcohol and marijuana by adolescents. Further more rigorous research is required to confirm this potential.</p

Moving to capture children’s attention: developing a methodology for measuring visuomotor attention

Attention underpins many activities integral to a child’s development. However, methodological limitations currently make large-scale assessment of children’s attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of ‘Visual Motor Attention’ (VMA) - a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method’s core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults’ attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action)

Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights