Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

No evidence for UV-based nest-site selection in sticklebacks

BACKGROUND: Nests are built in various animal taxa including fish. In systems with exclusive male parental care, the choice of a nest site may be an important component of male fitness. The nest site may influence male attractiveness as a mate, and male, embryo, and juvenile survival probabilities. Reproductively active three-spined stickleback males establish and defend a territory in which they build a nest. Territories can differ remarkably in qualities that influence male and female reproductive success like predation risk or abiotic factors such as dissolved oxygen concentration or lighting conditions. The latter may be important because in sticklebacks the extended visual capability into the ultraviolet (UV) wave range plays a role in female mate choice. Males are thus expected to be choosy about the habitat in which they will build their nest. RESULTS: We tested nest-site choice in male three-spined sticklebacks with respect to different UV lighting conditions. Reproductively active males were given the simultaneous choice to build their nest either in an UV-rich (UV+) or an UV-lacking (UV-) environment. Males exhibited no significant nest-site preferences with respect to UV+ or UV-. However, larger males and also heavier ones completed their nests earlier. CONCLUSION: We found that UV radiation as well as differences in luminance had no influence on nest-site choice in three-spined sticklebacks. Males that built in the UV-rich environment were not different in any trait (body traits and UV reflection traits) from males that built in the UV-poor environment. There was a significant effect of standard length and body mass on the time elapsed until nest completion in the UV experiment. The larger and heavier a male, the faster he completed his nest. In the brightness control experiment there was a significant effect only of body mass on the duration of nest completion. Whether nest building preferences with respect to UV lighting conditions are context dependent needs to be tested for instance by nest-site choice experiment under increased predation risk

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

<p>Abstract</p> <p>Purpose</p> <p>Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT.</p> <p>Method and Materials</p> <p>Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed.</p> <p>Results</p> <p>At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation.</p> <p>Conclusion</p> <p>Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.</p

An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia involves a series of reactions which ultimately influence the final volume of a brain infarction. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of the cerebral response to ischemia and impact the resultant stroke volume. The final volume of a cerebral infarct is important as it correlates with the morbidity and mortality associated with non-lacunar ischemic strokes.</p> <p>Methods</p> <p>The proteins encoded by the methylenetetrahydrofolate reductase (<it>MTHFR</it>) and glutathione S-transferase omega-1 (<it>GSTO-1</it>) genes are, through oxidative mechanisms, key participants in the cerebral response to ischemia. On the basis of these biological activities, they were selected as candidate genes for further investigation. We analyzed the C677T polymorphism in the <it>MTHFR </it>gene and the C419A polymorphism in the <it>GSTO-1 </it>gene in 128 patients with non-lacunar ischemic strokes.</p> <p>Results</p> <p>We found no significant association of either the <it>MTHFR </it>(p = 0.72) or <it>GSTO-1 </it>(p = 0.58) polymorphisms with cerebral infarct volume.</p> <p>Conclusion</p> <p>Our study shows no major gene effect of either the <it>MTHFR </it>or <it>GSTO-1 </it>genes as a modifier of ischemic stroke volume. However, given the relatively small sample size, a minor gene effect is not excluded by this investigation.</p

Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia

A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure. Confirmation of etiology by laboratory testing is warranted in such cases. Rapid antigen and immunofluorescence testing are useful screening tests, but have limited sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture. The most effective preventive measure is annual influenza vaccination in selected individuals. Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results. Neuraminidase inhibitors (NI) are the agents of choice

Species-specific behavioral patterns correlate with differences in synaptic connections between homologous mechanosensory neurons

We characterized the behavioral responses of two leech species, Hirudo verbana and Erpobdella obscura, to mechanical skin stimulation and examined the interactions between the pressure mechanosensory neurons (P cells) that innervate the skin. To quantify behavioral responses, we stimulated both intact leeches and isolated body wall preparations from the two species. In response to mechanical stimulation, Hirudo showed local bending behavior, in which the body wall shortened only on the side of the stimulation. Erpobdella, in contrast, contracted both sides of the body in response to touch. To investigate the neuronal basis for this behavioral difference, we studied the interactions between P cells. Each midbody ganglion has four P cells; each cell innervates a different quadrant of the body wall. Consistent with local bending, activating any one P cell in Hirudo elicited polysynaptic inhibitory potentials in the other P cells. In contrast, the P cells in Erpobdella had excitatory polysynaptic connections, consistent with the segment-wide contraction observed in this species. In addition, activating individual P cells caused asymmetrical body wall contractions in Hirudo and symmetrical body wall contractions in Erpobdella. These results suggest that the different behavioral responses in Erpobdella and Hirudo are partly mediated by interactions among mechanosensory cells

The use of race, ethnicity and ancestry in human genetic research

Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008–2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001–2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using ‘race’, ‘ethnicity’ or ‘ancestry’ defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using ‘ancestry’ being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed

Global Taxonomic Diversity of Anomodonts (Tetrapoda, Therapsida) and the Terrestrial Rock Record Across the Permian-Triassic Boundary

The end-Permian biotic crisis (∼252.5 Ma) represents the most severe extinction event in Earth's history. This paper investigates diversity patterns in Anomodontia, an extinct group of therapsid synapsids (‘mammal-like reptiles’), through time and in particular across this event. As herbivores and the dominant terrestrial tetrapods of their time, anomodonts play a central role in assessing the impact of the end-Permian extinction on terrestrial ecosystems. Taxonomic diversity analysis reveals that anomodonts experienced three distinct phases of diversification interrupted by the same number of extinctions, i.e. an end-Guadalupian, an end-Permian, and a mid-Triassic extinction. A positive correlation between the number of taxa and the number of formations per time interval shows that anomodont diversity is biased by the Permian-Triassic terrestrial rock record. Normalized diversity curves indicate that anomodont richness continuously declines from the Middle Permian to the Late Triassic, but also reveals all three extinction events. Taxonomic rates (origination and extinction) indicate that the end-Guadalupian and end-Permian extinctions were driven by increased rates of extinction as well as low origination rates. However, this pattern is not evident at the final decline of anomodont diversity during the Middle Triassic. Therefore, it remains unclear whether the Middle Triassic extinction represents a gradual or abrupt event that is unique to anomodonts or more common among terrestrial tetrapods. The end-Permian extinction represents the most distinct event in terms of decline in anomodont richness and turnover rates

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain