Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/1/feb213699.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/2/feb213699_am.pd

Two rapid assays for screening of patulin biodegradation

Artículo sobre distintos ensayos para comprobar la biodegradación de la patulinaThe mycotoxin patulin is produced by the blue mould pathogen Penicillium expansum in rotting apples during postharvest storage. Patulin is toxic to a wide range of organisms, including humans, animals, fungi and bacteria. Wash water from apple packing and processing houses often harbours patulin and fungal spores, which can contaminate the environment. Ubiquitous epiphytic yeasts, such as Rhodosporidium kratochvilovae strain LS11 which is a biocontrol agent of P. expansum in apples, have the capacity to resist the toxicity of patulin and to biodegrade it. Two non-toxic products are formed. One is desoxypatulinic acid. The aim of the work was to develop rapid, high-throughput bioassays for monitoring patulin degradation in multiple samples. Escherichia coli was highly sensitive to patulin, but insensitive to desoxypatulinic acid. This was utilized to develop a detection test for patulin, replacing time-consuming thin layer chromatography or high-performance liquid chromatography. Two assays for patulin degradation were developed, one in liquid medium and the other in semi-solid medium. Both assays allow the contemporary screening of a large number of samples. The liquid medium assay utilizes 96-well microtiter plates and was optimized for using a minimum of patulin. The semisolid medium assay has the added advantage of slowing down the biodegradation, which allows the study and isolation of transient degradation products. The two assays are complementary and have several areas of utilization, from screening a bank of microorganisms for biodegradation ability to the study of biodegradation pathways

Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in orderto address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior. (C) 2016 Elsevier B.V. All rights reserved.CAPES (Coordenagdo de Aperfeicoamento de Pessoal de Nivel Superior)CNPq (Conselho Nacional de Desenvolvimento Cientffico e Tecnologico)FAPESP (Fundacao de Amparo a Pesquisa do Estado de sao Paulo), BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, SP, BrazilUniv Liverpool, Inst Integrat Biol, Dept Biochem, Liverpool, Merseyside, EnglandUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilUniv Houston, Coll Optometry, TOSI, Houston, TX USAUniv Fed Sao Paulo, Grp Interdisciplinar Ciencias Exatas Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilUniv Fed Sao Paulo, Grp Interdisciplinar Ciencias Exatas Saude, Sao Paulo, SP, BrazilFAPESP: 15/08782-3FAPESP: 15/03964-6Web of Scienc

First-in-class, first-in-human phase I results of targeted agents: Highlights of the 2008 American Society of Clinical Oncology meeting

This review summarizes phase I trial results of 11 drugs presented at the American Society of Clinical Oncology meeting held in Chicago IL from May 30 to June 3rd 2008: BMS-663513, CT-322, CVX-045, GDC-0449, GRN163L, LY2181308, PF-00562271, RAV12, RTA 402, XL765, and the survivin vaccine

Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study

The vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. © 2013 Horn et al

High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change

Diet, physical exercise and cognitive behavioral training as a combined workplace based intervention to reduce body weight and increase physical capacity in health care workers - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Health care workers comprise a high-risk workgroup with respect to deterioration and early retirement. There is high prevalence of obesity and many of the workers are overweight. Together, these factors play a significant role in the health-related problems within this sector. The present study evaluates the effects of the first 3-months of a cluster randomized controlled lifestyle intervention among health care workers. The intervention addresses body weight, general health variables, physical capacity and musculoskeletal pain.</p> <p>Methods</p> <p>98 female, overweight health care workers were cluster-randomized to an intervention group or a reference group. The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during working hours 1 hour/week. Leisure time aerobic fitness was planned for 2 hour/week. The reference group was offered monthly oral presentations. Body weight, BMI, body fat percentage (bioimpedance), waist circumference, blood pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period.</p> <p>Results</p> <p>In an intention-to-treat analysis from pre to post tests, the intervention group significantly reduced body weight with 3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from 40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001) and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant difference between the intervention and control group (p < 0.001) on all measures. No effect of intervention was found in musculoskeletal pain, maximal oxygen uptake and muscle strength, but on aerobic fitness.</p> <p>Conclusion</p> <p>The significantly reduced body weight, body fat, waist circumference and blood pressure as well as increased aerobic fitness in the intervention group show the great potential of workplace health promotion among this high-risk workgroup. Long-term effects of the intervention remain to be investigated.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015716">NCT01015716</a></p

Species-speciWc defense strategies of vegetative versus reproductive blades of the PaciWc kelps Lessonia nigrescens and Macrocystis integrifolia

Chemical defense is assumed to be costly and therefore algae should allocate defense investments in a way to reduce costs and optimize their overall fitness. Thus, lifetime expectation of particular tissues and their contribution to the fitness of the alga may affect defense allocation. Two brown algae common to the SE Pacific coasts, Lessonia nigrescens Bory and Macrocystis integrifolia Bory, feature important ontogenetic differences in the development of reproductive structures; in L. nigrescens blade tissues pass from a vegetative stage to a reproductive stage, while in M. integrifolia reproductive and vegetative functions are spatially separated on different blades. We hypothesized that vegetative blades of L. nigrescens with important future functions are more (or equally) defended than reproductive blades, whereas in M. integrifolia defense should be mainly allocated to reproductive blades (sporophylls), which are considered to make a higher contribution to fitness. Herein, within-plant variation in susceptibility of reproductive and vegetative tissues to herbivory and in allocation of phlorotannins (phenolics) and N-compounds was compared. The results show that phlorotannin and N-concentrations were higher in reproductive blade tissues for both investigated algae. However, preferences by amphipod grazers (Parhyalella penai) for either tissue type differed between the two algal species. Fresh reproductive tissue of L. nigrescens was more consumed than vegetative tissue, while the reverse was found in M. integrifolia, thus confirming the original hypothesis. This suggests that future fitness function might indeed be a useful predictor of anti-herbivore defense in large, perennial kelps. Results from feeding assays with artificial pellets that were made with air-dried material and extract-treated Ulva powder indicated that defenses in live algae are probably not based on chemicals that can be extracted or remain intact after air-drying and grinding up algal tissues. Instead, anti-herbivore defense against amphipod mesograzers seems to depend on structural traits of living algae