Both Pre- and Postsynaptic Activity of Nsf Prevents Degeneration of Hair-Cell Synapses

Vesicle fusion contributes to the maintenance of synapses in the nervous system by mediating synaptic transmission, release of neurotrophic factors, and trafficking of membrane receptors. N-ethylmaleimide-sensitive factor (NSF) is indispensible for dissociation of the SNARE-complex following vesicle fusion. Although NSF function has been characterized extensively in vitro, the in vivo role of NSF in vertebrate synaptogenesis is relatively unexplored. Zebrafish possess two nsf genes, nsf and nsfb. Here, we examine the function of either Nsf or Nsfb in the pre- and postsynaptic cells of the zebrafish lateral line organ and demonstrate that Nsf, but not Nsfb, is required for maintenance of afferent synapses in hair cells. In addition to peripheral defects in nsf mutants, neurodegeneration of glutamatergic synapses in the central nervous system also occurs in the absence of Nsf function. Expression of an nsf transgene in a null background indicates that stabilization of synapses requires Nsf function in both hair cells and afferent neurons. To identify potential targets of Nsf-mediated fusion, we examined the expression of genes implicated in stabilizing synapses and found that transcripts for multiple genes including brain-derived neurotrophic factor (bdnf) were significantly reduced in nsf mutants. With regard to trafficking of BDNF, we observed a striking accumulation of BDNF in the neurites of nsf mutant afferent neurons. In addition, injection of recombinant BDNF protein partially rescued the degeneration of afferent synapses in nsf mutants. These results establish a role for Nsf in the maintenance of synaptic contacts between hair cells and afferent neurons, mediated in part via the secretion of trophic signaling factors

The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study

INTRODUCTION: Compliance with the ventilator care bundle affects the rate of ventilator-associated pneumonia. It was not known, however, whether compliance with sepsis care bundles has an impact on outcome. The aims of the present study were to determine the rate of compliance with 6-hour and 24-hour sepsis bundles and to determine the impact of the compliance on hospital mortality in patients with severe sepsis or septic shock. METHODS: We conducted a prospective observational study on 101 consecutive adult patients with severe sepsis or septic shock on medical or surgical wards, or in accident and emergency areas at two acute National Health Service Trust Teaching hospitals in England. The main outcome measures were: the rate of compliance with 6-hour and 24-hour sepsis care bundles adapted from the Surviving Sepsis Campaign guidelines on patients' clinical care; and the difference in hospital mortality between the compliant and the non-compliant groups. RESULTS: The median age of the patients was 69 years (interquartile range 51 to 78), and 53% were male. The sources of infection were sought and confirmed in 87 of 101 patients. The chest was the most common source (50%), followed by the abdomen (22%). The rate of compliance with the 6-hour sepsis bundle was 52%. Compared with the compliant group, the non-compliant group had a more than twofold increase in hospital mortality (49% versus 23%, relative risk (RR) 2.12 (95% confidence interval (CI) 1.20 to 3.76), P = 0.01) despite similar age and severity of sepsis. Compliance with the 24-hour sepsis bundle was achieved in only 30% of eligible candidates (21/69). Hospital mortality was increased in the non-compliant group from 29% to 50%, with a 76% increase in risk for death, although the difference did not reach statistical significance (RR 1.76 (95% CI 0.84 to 3.64), P = 0.16). CONCLUSION: Non-compliance with the 6-hour sepsis bundle was associated with a more than twofold increase in hospital mortality. Non-compliance with the 24-hour sepsis bundle resulted in a 76% increase in risk for hospital death. All medical staff should practise these relatively simple, easy and cheap bundles within a strict timeframe to improve survival rates in patients with severe sepsis and septic shock

Sustentación de caso: propuesta de un plan estratégico del ingreso al mercado peruano de una empesa del sector fast fashion

El siguiente trabajo tiene como objetivo investigar a profundidad el modelo de negocio de cada una de las empresas que forman parte del grupo “Fast Retailing”, el cual es reconocido no solo por los precios asequibles que ofrece y que se adaptan a casi todos los segmentos de mercado, sino también por la calidad en los productos que brinda. Dentro de las marcas del grupo se analizará a Uniqlo, Theory, Princesse Tam Tam, Gu y Comptoir des cotonniers y cómo estas han ido creciendo con el pasar de los años compitiendo hoy en día en el mercado global con los principales líderes mundiales como lo son: H&M, Zara, GAP, entre otros. Así mismo, se busca analizar la inversión de la empresa en nuevos mercados y evaluar lo que los distingue frente a la competencia en base a conceptos teóricos utilizados e información recolectada de libros, artículos y fuentes confiables para así elaborar conclusiones personales en base a resultados finales producto de investigación e identificar los factores de éxito junto con estrategias cruciales para su crecimiento y reconocimiento a nivel mundial

Neural mechanisms of body awareness in infants

The ability to differentiate one’s body from others is a fundamental aspect of social perception and has been shown to involve the integration of sense modalities attributable to the self. Though behavioral studies in infancy have investigated infants’ discrimination of body-related multisensory stimuli, whether they attribute this information as belonging to the self is still unknown. In human adults, neuroimaging studies have demonstrated the recruitment of a specific set of brain regions in response to body-related multisensory integration. To test whether the infant brain integrates this information similarly to adults, in a first functional near-infrared spectroscopy study we investigated the role of visual–proprioceptive feedback when temporal cues are manipulated by showing 5-month-old infants an online video of their own face while the infant was performing movements. To explore the role of body-related contingency further, in a second study we investigated whether cortical activation in response to self-initiated movements and external tactile stimulationwas similar to that found in the first study. Our results indicate that infants’ specialized cortical activation in response to body-related contingencies is similar to brain activation seen in response to body awareness in adults

The Notion and Assessment of “Predatory” in Scholarly Publishing

We set out to create an openly accessible, transparent evaluation tool that engages with the nuance of publishing circumstances and creates a clear record of the assessment. Without redefining or seeking to categorize journals, we hope to provide information in a format that allows authors to make considered choices and librarians to record the efforts of labor they likely already engage in. Working with the inherent humor of meta-analysis, we created Reviews: The Journal of Journal Reviews (RJJR). RJJR will publish nuanced, context-centered reviews of scholarly journals based on available, observable evidence. The “Journal Reviews”—peer-reviewed evaluations of journals across disciplines, subscription models, and regions—will offer researchers an alternative tool for evaluating unfamiliar publications while also modeling contextual evaluation. We are dedicated to the process of journal evaluation as an educational tool as well as a resource for the community

Eagle Adventure: School-Based Type 2 Diabetes Prevention Program Results in Improved Outcomes Related to Food and Physical Activity

The Eagle Adventure program was designed as a semester-long, SNAP-Ed program to address food and physical activity choices important for prevention of type 2 diabetes, obesity, and other chronic diseases. The program was developed for implementation in Grades 1-3. This article presents findings from two participating grade centers inclusive of Grades1-2. The elementary school-based program not only addresses health-related behaviors in a culturally relevant and responsive way, but also serves as a potential model for promoting diversity inclusion in Extension programming

Comparison of Methods for the Purification of Alpha-1 Acid Glycoprotein from Human Plasma

Alpha-1 acid glycoprotein (AGP) is a highly glycosylated, negatively charged plasma protein suggested to have anti-inflammatory and/or immunomodulatory activities. Purification of AGP could be simplified if methods that exploit its high solubility under chemically harsh conditions could be demonstrated to leave the protein in its native conformation. Procedures involving exposure of AGP to hot phenol or sulphosalicylic acid (SSA) were compared to solely chromatographic methods. Hot phenol-purified AGP was more rapidly cleared from mice in vivo following intravenous injection than chromatographically purified AGP. In contrast, SSA-purified AGP demonstrated an identical in vivo clearance profile and circular dichroism spectrum to chromatographically purified AGP. Similarly, no differences in susceptibility to enzymatic deglycosylation or reactivity with Sambucus nigra lectin were detected between AGP purified via the two methods. Incorporation of the SSA step in the purification scheme for AGP eliminated the need for a large (4 mL resin/mL of plasma) initial chromatographic step and simplified its purification without causing any detectable distortion in the conformation of the protein. Confirmation that this procedure is nondenaturing will simplify AGP purification and investigation of its possible biological roles in laboratory animals

In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall

Alpha-1 acid glycoprotein (AGP) is a highly glycosylated plasma protein that exerts vasoprotective effects. We hypothesized that AGP's N-linked glycans govern its rate of clearance from the circulation, and followed the disappearance of different forms of radiolabeled human AGP from the plasma of rabbits and mice. Enzymatic deglycosylation of human plasma-derived AGP (pdAGP) by Peptide: N-Glycosidase F yielded a mixture of differentially deglycosylated forms (PNGase-AGP), while the introduction of five Asn to Gln mutations in recombinant Pichia pastoris-derived AGP (rAGP-N(5)Q) eliminated N-linked glycosylation. PNGase-AGP was cleared from the rabbit circulation 9-fold, and rAGP-N(5)Q, 46-fold more rapidly than pdAGP, primarily via a renal route. Pichia pastoris-derived wild-type rAGP differed from pdAGP in expressing mannose-terminated glycans, and, like neuraminidase-treated pdAGP, was more rapidly removed from the rabbit circulation than rAGP-N(5)Q. Systemic hyaluronidase treatment of mice transiently decreased pdAGP clearance. AGP administration to mice reduced vascular binding of hyaluronic acid binding protein in the liver microcirculation and increased its plasma levels. Our results support a critical role of N-linked glycosylation of AGP in regulating its in vivo clearance and an influence of a hyaluronidase-sensitive component of the vessel wall on its transendothelial passage