The structure of the hantavirus zinc finger domain is conserved and represents the only natively folded region of the Gn cytoplasmic tail

Hantaviruses, of the family Bunyaviridae, are present throughout the world and cause a variety of infections ranging from the asymptomatic to mild and severe hemorrhagic fevers. Hantaviruses are enveloped anti-sense RNA viruses that contain three genomic segments that encode for a nucleocapsid protein, two membrane glycoproteins (Gn and Gc), and an RNA polymerase. Recently, the pathogenicity of hantaviruses has been mapped to the carboxyl end of the 150 residue Gn cytoplasmic tail. The Gn tail has also been shown to play a role in binding the ribonucleoprotein (RNP), a step critical for virus assembly. In this study, we use NMR spectroscopy to compare the structure of a Gn tail zinc finger domain of both a pathogenic (Andes) and a non-pathogenic (Prospect Hill) hantavirus. We demonstrate that despite a stark difference in the virulence of both of these viruses, the structure of the Gn core zinc finger domain is largely conserved in both strains. We also use NMR backbone relaxation studies to demonstrate that the regions of the Andes virus Gn tail immediately outside the zinc finger domain, sites known to bind the RNP, are disordered and flexible, thus intimating that the zinc finger domain is the only structured region of the Gn tail. These structural observations provide further insight into the role of the Gn tail during viral assembly as well as its role in pathogenesis

Glycyrrhizic Acid Can Attenuate Metabolic Deviations Caused by a High-Sucrose Diet without Causing Water Retention in Male Sprague-Dawley Rats

Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time

Cerebral Regulation In Different Maximal Aerobic Exercise Modes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We investigated cerebral responses, simultaneously with peripheral and ratings of perceived exertion (RPE) responses, during different VO2MAX-matched aerobic exercise modes. Nine cyclists (VO2MAX of 57.5 +/- 6.2 ml.kg(-1).min(-1)) performed a maximal, controlled-pace incremental test (MIT) and a self-paced 4 km time trial (TT4km). Measures of cerebral (COX) and muscular (MOX) oxygenation were assessed throughout the exercises by changes in oxy-(O(2)Hb) and deoxy-hemoglobin (HHb) concentrations over the prefrontal cortex (PFC) and vastus lateralis (VL) muscle, respectively. Primary motor cortex (PMC) electroencephalography (EEG), VL, and rectus femoris EMG were also assessed throughout the trials, together with power output and cardiopulmonary responses. The RPE was obtained at regular intervals. Similar motor output (EMG and power output) occurred from 70% of the duration in MIT and TT4km, despite the greater motor output, muscle deoxygenation (down arrow MOX) and cardiopulmonary responses in TT4km before that point. Regarding cerebral responses, there was a lower COX (1, O(2)Hb concentrations in PFC) at 20, 30, 40, 50 and 60%, but greater at 100% of the TT4km duration when compared to MIT The alpha wave EEG in PMC remained constant throughout the exercise modes, with greater values in TT4km. The RPE was maximal at the endpoint in both exercises, but it increased slower in TT4km than in MIT. Results showed that similar motor output and effort tolerance were attained at the closing stages of different VO2MAX-matched aerobic exercises, although the different disturbance until that point. Regardless of different COX responses during most of the exercises duration, activation in PMC was preserved throughout the exercises, suggesting that these responses may be part of a centrally coordinated exercise regulation.7FAPESP-Brazil [2010/01317-0]FAPESP [2005/56578-4, 2015/13096-1]CNPq-Brazil [480702/2010-1, 303085/2015-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia

The authors would like to thank the Deutsche José Carreras Leukämie-Stiftung, Inocente Inocente Foundation, the Ministry of Economy of Spain (SAF2015- 67919-R), Consejería de Salud de la Junta de Andalucía (Pl-0245-2017, CS2016- 3), BBVA Foundation, Francisco-Cobos Foundation, Fero Foundation and AECC Foundation for funding Pedro P. Medinas’s lab. Álvaro Andrades is supported by an FPU17/00067 PhD fellowship, Alberto M. Arenas is supported by an FPU17/01258 PhD fellowship, Paola Peinado is supported by a La Caixa Foundation PhD Fellowship (LCF/BQ/DE15/10360019), Isabel F. Coira was supported by a PhD FPI-fellowship (BES-2013-064596), Daniel J. García is supported by a Fundación Benéfica Anticáncer Santa Cándida y San Francisco Javier PhD fellowship and Juan Carlos Álvarez-Pérez is supported by a Marie Sklodowska Curie action (H2020-MSCA-IF-2018). The funding agencies had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors would also like to thank the Biobanc de l’Hospital Infantil Sant Joan de Déu per a la Investigació, integrated in the Spanish Biobank Network of ISCIII, as well as Asociación Malagueña para la Investigación en Leucemias (AMPILE), for the sample and data procurement

Fungal entomopathogens: new insights on their ecology

An important mechanism for insect pest control should be the use of fungal entomopathogens. Even though these organisms have been studied for more than 100 y, their effective use in the field remains elusive. Recently, however, it has been discovered that many of these entomopathogenic fungi play additional roles in nature. They are endophytes, antagonists of plant pathogens, associates with the rhizosphere, and possibly even plant growth promoting agents. These findings indicate that the ecological role of these fungi in the environment is not fully understood and limits our ability to employ them successfully for pest management. In this paper, we review the recently discovered roles played by many entomopathogenic fungi and propose new research strategies focused on alternate uses for these fungi. It seems likely that these agents can be used in multiple roles in protecting plants from pests and diseases and at the same time promoting plant growth

Performance of a Yeast-mediated Biological Fuel Cell

Saccharomyces cerevisiae present in common Baker’s yeast was used in a microbial fuel cell in which glucose was the carbon source. Methylene blue was used as the electronophore in the anode compartment, while potassium ferricyanide and methylene blue were tested as electron acceptors in the cathode compartment. Microbes in a mediator-free environment were used as the control. The experiment was performed in both open and closed circuit configurations under different loads ranging from 100 kΩ to 400Ω. The eukaryotic S. cerevisiae-based fuel cell showed improved performance when methylene blue and ferricyanide were used as electron mediators, rendering a maximum power generation of 146.71±7.7 mW/m3. The fuel cell generated a maximum open circuit voltage of 383.6±1.5 mV and recorded a maximum efficiency of 28±1.8 % under 100 kΩ of external load

Mixing at the head of a canyon : a laboratory investigation of fluid exchanges in a rotating, stratified basin

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C12004, doi:10.1029/2006JC003667.Observations indicate that oceanic mixing is intensified near the head of submarine canyons. How the presence of canyon walls affects the local production and distribution of mixed fluid is an open question. These dynamics are addressed through rotating tank experiments which impose mixing at middepth at the closed end of a channel open to a larger body of water. Turbulence is generated in a linearly stratified fluid with initial buoyancy frequency N by means of a single bar oscillated with frequency ω. The mixed fluid quickly reaches a steady state height h ∼ (ω/N)1/2 independent of the Coriolis frequency f and collapses into the channel interior. A small percentage of the fluid exported from the turbulent zone enters a boundary current. The bulk forms a cyclonic circulation in front of the bar. As the recirculation cell expands to fill the channel, it restricts horizontal entrainment into the turbulent zone. Mixed fluid flux decays with time as t inline equation and is dependent on the size of the mixing zone and the balance between turbulence, rotation, and stratification. The recirculation cell is confined within the channel, and export of mixed fluid into the basin is restricted to the weak boundary current. As horizontal entrainment is shut down, long-term production of mixed fluid relies more on vertical entrainment. However, the scalings indicate that short-term dynamics are the most applicable to oceanic conditions.This work was supported by the Ocean Ventures Fund, the Westcott Fund, and the WHOI Academic Programs Office. Financial support was also provided by the National Science Foundation through grant OCE-9616949

Doctor, how much weight will I lose? - a new individualized predictive model for weight loss

Bariatric surgery is an effective treatment for weight loss, but the patient’s ability to reach a sustained weight loss depends upon several technical and individual factors. Creating an easy model that adapts bariatric surgery’s weight loss goals for each patient is very important for pre-surgery and follow-up evaluations.info:eu-repo/semantics/publishedVersio

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease

Abstract Background Long-acting muscarinic antagonist/long-acting β 2 -agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI). Methods This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD (NCT01085045). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV 1 AUC 0–12 ) on Day 7 relative to baseline FEV 1 . Secondary endpoints included pharmacokinetics and safety. Results GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV 1 AUC 0–12 after 7 days’ treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated. Conclusions GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD. Trial registration ClinicalTrials.gov NCT01085045. Registered 9 March 2010