Cell Culture Modeling to Test Therapies Against Hyperglycemia-Mediated Oxidative Stress and Injury

The concept that oxidative stress is a key mediator of nerve injury in diabetes has led us to design therapies that target oxidative stress mechanisms. Using an in vitro model of glucose-treated dorsal root ganglion (DRG) neurons in culture, we can examine both free radical generation, using fluorimetric probes for reactive oxygen species, and cell death via the TUNEL assay. The cell culture system is scaled down to a 96-well plate format, and so is well suited to high-throughput screening. In the present study, we test the ability of three drugs, nicotinamide, allopurinol, and α-lipoic acid, alone and in combination to prevent DRG neuron oxidative stress and cell death. This combination of drugs is currently in clinical trial in type 1 diabetic patients. We demonstrate independent effects on oxidative stress and neuronal survival for the three drugs, and neuronal protection using the three drugs in combination. The data strengthen the rationale for the current clinical trial. In addition, we describe an effective tool for rapid preclinical testing of novel therapies against diabetic neuropathy. Antioxid. Redox Signal. 7, 1494–1506.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63115/1/ars.2005.7.1494.pd

Evaluation of the Algorithms and Parameterizations for Ground Thawing and Freezing Simulation in Permafrost Regions

Ground thawing and freezing depths (GTFDs) strongly influence the hydrology and energy balances of permafrost regions. Current methods to simulate GTFD differ in algorithm type, soil parameterization, representation of latent heat, and unfrozen water content. In this study, five algorithms (one semiempirical, two analytical, and two numerical), three soil thermal conductivity parameterizations, and three unfrozen water parameterizations were evaluated against detailed field measurements at four field sites in Canada’s discontinuous permafrost region. Key findings include: (1) de Vries’ parameterization is recommended to determine the thermal conductivity in permafrost soils; (2) the three unfrozen water parameterization methods exhibited little difference in terms of GTFD simulations, yet the segmented linear function is the simplest to be implemented; (3) the semiempirical algorithm reasonably simulates thawing at permafrost sites and freezing at seasonal frost sites with site-specific calibration. However, large interannual and intersite variations in calibration coefficients limit its applicability for dynamic analysis; (4) when driven by surface forcing, analytical algorithms performed marginally better than the semiempirical algorithm. The inclusion of bottom forcing improved analytical algorithm performance, yet their results were still poor compared with those achieved by numerical algorithms; (5) when supplied with the optimal inputs, soil parameterizations, and model configurations, the numerical algorithm with latent heat treated as an apparent heat capacity achieved the best GTFD simulations among all algorithms at all sites. Replacing the observed bottom temperature with a zero heat flux boundary condition did not significantly reduce simulation accuracy, while assuming a saturated profile caused large errors at several sites

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

Migrations and habitat use of the smooth hammerhead shark (Sphyrna zygaena) in the Atlantic Ocean

The smooth hammerhead shark, Sphyrna zygaena, is a cosmopolitan semipelagic shark captured as bycatch in pelagic oceanic fisheries, especially pelagic longlines targeting swordfish and/or tunas. From 2012 to 2016, eight smooth hammerheads were tagged with Pop-up Satellite Archival Tags in the inter-tropical region of the Northeast Atlantic Ocean, with successful transmissions received from seven tags (total of 319 tracking days). Results confirmed the smooth hammerhead is a highly mobile species, as the longest migration ever documented for this species (> 6600 km) was recorded. An absence of a diel vertical movement behavior was noted, with the sharks spending most of their time at surface waters (0-50 m) above 23 degrees C. The operating depth of the pelagic long-line gear was measured with Minilog Temperature and Depth Recorders, and the overlap with the species vertical distribution was calculated. The overlap is taking place mainly during the night and is higher for juveniles (similar to 40% of overlap time). The novel information presented can now be used to contribute to the provision of sustainable management tools and serve as input for Ecological Risk Assessments for smooth hammerheads caught in Atlantic pelagic longline fisheries.Oceanario de Lisboa through Project "SHARK-TAG: Migrations and habitat use of the smooth hammerhead shark in the Atlantic Ocean"; Investigador-FCT from the Portuguese Foundation for Science and Technology (FCT, Fundacao para a Ciencia e Tecnologia) [Ref: IF/00253/2014]; EU European Social Fund; Programa Operacional Potencial Human

Imitation, mirror neurons and autism

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and ‘theory of mind’ abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

Regional Endothermy in a Coral Reef Fish?

Although a few pelagic species exhibit regional endothermy, most fish are regarded as ectotherms. However, we document significant regional endothermy in a benthic reef fish. Individual steephead parrotfish, Chlorurus microrhinos (Labridae, formerly Scaridae) were tagged and their internal temperatures were monitored for a 24 h period using active acoustic telemetry. At night, on the reef, C. microrhinos were found to maintain a consistent average peritoneal cavity temperature 0.16±0.005°C (SE) warmer than ambient. Diurnal internal temperatures were highly variable for individuals monitored on the reef, while in tank-based trials, peritoneal cavity temperatures tracked environmental temperatures. The mechanisms responsible for a departure of the peritoneal cavity temperature from environmental temperature occurred in C. microrhinos are not yet understood. However, the diet and behavior of the species suggests that heat in the peritoneal cavity may result primarily from endogenous thermogenesis coupled with physiological heat retention mechanisms. The presence of limited endothermy in C. microrhinos indicates that a degree of uncertainty may exist in the manner that reef fish respond to their thermal environment. At the very least, they do not always appear to respond to environmental temperatures as neutral thermal vessels and do display limited, but significant, visceral warming

Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA

Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Rα) and nonbinding affinity-enhancing (GM-CSF-Rβ) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Rα–encoding alleles (CSF2RA). One was a 1.6-Mb deletion in the pseudoautosomal region of one maternal X chromosome encompassing CSF2RA. The other, a point mutation in the paternal X chromosome allele encoding a G174R substitution, altered an N-linked glycosylation site within the cytokine binding domain and glycosylation of GM-CSF-Rα, severely reducing GM-CSF binding, receptor signaling, and GM-CSF–dependent functions in primary myeloid cells. Transfection of cloned cDNAs faithfully reproduced the signaling defect at physiological GM-CSF concentrations. Interestingly, at high GM-CSF concentrations similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow progression of disease in these children. These results establish that GM-CSF signaling is critical for surfactant homeostasis in humans and demonstrate that mutations in CSF2RA cause familial PAP

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis