Psychiatric Molecular Genetics and the Ethics of Social Promises

A recent literature review of commentaries and ‘state of the art’ articles from researchers in psychiatric genetics (PMG) offers a consensus about progress in the science of genetics, disappointments in the discovery of new and effective treatments, and a general optimism about the future of the field. I argue that optimism for the field of psychiatric molecular genetics (PMG) is overwrought, and consider progress in the field in reference to a sample estimate of US National Institute of Mental Health funding for this paradigm for the years 2008 and 2009. I conclude that the amounts of financial investment in PMG is questionable from an ethical perspective, given other research and clinical needs in the USA.     

EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart

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Sampling for Explosives-Residues at Fort Greely,Alaska

Fort Greely, Alaska has an extensive complex of weapon training and testing areas located on lands withdrawn from the public domain under the Military Lands Withdrawal Act (PL106-65). The Army has pledged to implement a program to identify possible munitions contamination. Because of the large size (344,165,000 m²) of the high hazard impact areas, characterization of these constituents will be difficult. We used an authoritative sampling design to find locations most likely to contain explosives-residues on three impact areas. We focused our sampling on surface soils and collected multi-increment and discrete samples at locations of known firing events and from areas on the range that had craters, pieces of munitions, targets, or a designation as a firing point. In the two impact areas used primarily by the Army, RDX was the most frequently detected explosive. In the impact area that was also used by the Air Force, TNT was the most frequently detected explosive. Where detected, the explosives concentrations generally were low (<0.05 mg/kg) except in soils near low-order detonations, where the explosive-filler was in contact with the soil surface. These low-order detonations potentially can serve as localized sources for groundwater contamination if positioned in recharge areas.     

Predator detection and avoidance by starlings under differing scenarios of predation risk

Practically all animals must find food while avoiding predators.An individual's perception of predation risk may depend on manyfactors, such as distance to refuge and group size, but it isunclear whether individuals respond to different factors ina similar manner. We tested whether flocks of foraging starlingsresponded in the same way to an increased perception of predationrisk by assessing three factors: (1) neighbor distances, (2)habitat obstruction, and (3) recent exposure to a predator.We found that in all three scenarios of increased risk, starlingsreduced their interscan intervals (food-searching bouts), whichincreased the frequency of their vigilance periods. We thenexamined how one of these factors, habitat obstruction, affectedescape speed by simulating an attack with a model predator.Starlings were slower to respond in visually obstructed habitats(long grass swards) and slower when they had their head downin obstructed habitats than when they had their head down inopen habitats. In addition, reaction times were quicker whenstarlings could employ their peripheral fields of vision. Ourresults demonstrate that different sources of increased riskcan generate similar behavioral responses within a species.The degree of visibility in the physical and social environmentaffects both the actual and perceived risk of predation.     

Quantifying Biomass Changes of Single CD8+ T Cells during Antigen Specific Cytotoxicity

Existing approaches that quantify cytotoxic T cell responses rely on bulk or surrogate measurements which impede the direct identification of single activated T cells of interest. Single cell microscopy or flow cytometry methodologies typically rely on fluorescent labeling, which limits applicability to primary cells such as human derived T lymphocytes. Here, we introduce a quantitative method to track single T lymphocyte mediated cytotoxic events within a mixed population of cells using live cell interferometry (LCI), a label-free microscopy technique that maintains cell viability. LCI quantifies the mass distribution within individual cells by measuring the phase shift caused by the interaction of light with intracellular biomass. Using LCI, we imaged cytotoxic T cells killing cognate target cells. In addition to a characteristic target cell mass decrease of 20–60% over 1–4 h following attack by a T cell, there was a significant 4-fold increase in T cell mass accumulation rate at the start of the cytotoxic event and a 2–3 fold increase in T cell mass relative to the mass of unresponsive T cells. Direct, label-free measurement of CD8+ T and target cell mass changes provides a kinetic, quantitative assessment of T cell activation and a relatively rapid approach to identify specific, activated patient-derived T cells for applications in cancer immunotherapy.     

Passive irrigation and functional morphology of crustacean burrows in a tropical mangrove swamp

Flushing measurements and a resin cast of a burrow inhabited by Sesarma messa and Alpheus cf macklay were taken from a Rhizophoraspp. forest. The burrow had 9 openings and occupied a swamp surface area of 0.64 m². Passive irrigation of the burrow was investigated by recording change in conductivity of burrow water in a chamber 45 cm below the swamp surface during tidal inundation of the swamp. The chamber was completely flushed within approximately one hour, i.e. by a single tidal event. Burrow morphology was determined by means of resin casting. The investigated burrow was of discrete structure, with an overall depth of 1.2 m and a total volume of 68 l, i.e. ca. 9% of the volume of swamp soil. The below ground surface area of chambers and tunnels was 3.8 m². The mean and maximum chamber/tunnel diameter was 7 cm and 11 cm respectively. The soil in the close vicinity of the burrow was extensively penetrated by roots, and any two parts of the burrow were located no further than 20 cm away from each other. By reducing diffusion distances within the soil and by being well flushed, the burrows provide an efficient mechanism for removal of excess salt accumulated in the soil around mangrove roots due to exclusion.     

Retinal Changes Precede Visual Dysfunction in the Complement Factor H Knockout Mouse

We previously reported that aged mice lacking complement factor H (CFH) exhibit visual defects and structural changes in the retina. However, it is not known whether this phenotype is age-related or is the consequence of disturbed development. To address this question we investigated the effect of Cfh gene deletion on the retinal phenotype of young and mid-age mice. Cfh ^−/− mouse eyes exhibited thickening of the retina and reduced nuclear density, but relatively normal scotopic and photopic electroretinograms. At 12 months there was evidence of subtle astroglial activation in the Cfh ^−/− eyes, and significant elevation of the complement regulator, decay-accelerating factor (DAF) in Müller cells. In the retinal pigment epithelium (RPE) of young control and Cfh ^−/− animals mitochondria and melanosomes were oriented basally and apically respectively, whereas the apical positioning of melanosomes was significantly perturbed in the mid-age Cfh ^−/− RPE. We conclude that deletion of Cfh in the mouse leads to defects in the retina that precede any marked loss of visual function, but which become progressively more marked as the animals age. These observations are consistent with a lifelong role for CFH in retinal homeostasis.