Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Microscopic optical buffering in a harmonic potential

In the early days of quantum mechanics, Schrödinger noticed that oscillations of a wave packet in a one-dimensional harmonic potential well are periodic and, in contrast to those in anharmonic potential wells, do not experience distortion over time. This original idea did not find applications up to now since an exact one-dimensional harmonic resonator does not exist in nature and has not been created artificially. However, an optical pulse propagating in a bottle microresonator (a dielectric cylinder with a nanoscale-high bump of the effective radius) can exactly imitate a quantum wave packet in the harmonic potential. Here, we propose a tuneable microresonator that can trap an optical pulse completely, hold it as long as the material losses permit, and release it without distortion. This result suggests the solution of the long standing problem of creating a microscopic optical buffer, the key element of the future optical signal processing devices

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

Surface and Temporal Biosignatures

Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

A European study investigating patterns of transition from home care towards institutional dementia care: the protocol of a RightTimePlaceCare study

<p>Abstract</p> <p>Background</p> <p>Health care policies in many countries aim to enable people with dementia to live in their own homes as long as possible. However, at some point during the disease the needs of a significant number of people with dementia cannot be appropriately met at home and institutional care is required. Evidence as to best practice strategies enabling people with dementia to live at home as long as possible and also identifying the right time to trigger admission to a long-term nursing care facility is therefore urgently required. The current paper presents the rationale and methods of a study generating primary data for best-practice development in the transition from home towards institutional nursing care for people with dementia and their informal caregivers. The study has two main objectives: 1) investigate country-specific factors influencing institutionalization and 2) investigate the circumstances of people with dementia and their informal caregivers in eight European countries. Additionally, data for economic evaluation purposes are being collected.</p> <p>Methods/design</p> <p>This paper describes a prospective study, conducted in eight European countries (Estonia, Finland, France, Germany, Netherlands, Sweden, Spain, United Kingdom). A baseline assessment and follow-up measurement after 3 months will be performed. Two groups of people with dementia and their informal caregivers will be included: 1) newly admitted to institutional long-term nursing care facilities; and 2) receiving professional long-term home care, and being at risk for institutionalization. Data will be collected on outcomes for people with dementia (e.g. quality of life, quality of care), informal caregivers (e.g. caregiver burden, quality of life) and costs (e.g. resource utilization). Statistical analyses consist of descriptive and multivariate regression techniques and cross-country comparisons.</p> <p>Discussion</p> <p>The current study, which is part of a large European project 'RightTimePlaceCare', generates primary data on outcomes and costs of long-term nursing care for people with dementia and their informal caregivers, specifically focusing on the transition from home towards institutional care. Together with data collected in three other work packages, knowledge gathered in this study will be used to inform and empower patients, professionals, policy and related decision makers to manage and improve health and social dementia care services.</p

Hawk Eyes II: Diurnal Raptors Differ in Head Movement Strategies When Scanning from Perches

Background Relatively little is known about the degree of inter-specific variability in visual scanning strategies in species with laterally placed eyes (e.g., birds). This is relevant because many species detect prey while perching; therefore, head movement behavior may be an indicator of prey detection rate, a central parameter in foraging models. We studied head movement strategies in three diurnal raptors belonging to the Accipitridae and Falconidae families. Methodology/Principal Findings We used behavioral recording of individuals under field and captive conditions to calculate the rate of two types of head movements and the interval between consecutive head movements. Cooper\u27s Hawks had the highest rate of regular head movements, which can facilitate tracking prey items in the visually cluttered environment they inhabit (e.g., forested habitats). On the other hand, Red-tailed Hawks showed long intervals between consecutive head movements, which is consistent with prey searching in less visually obstructed environments (e.g., open habitats) and with detecting prey movement from a distance with their central foveae. Finally, American Kestrels have the highest rates of translational head movements (vertical or frontal displacements of the head keeping the bill in the same direction), which have been associated with depth perception through motion parallax. Higher translational head movement rates may be a strategy to compensate for the reduced degree of eye movement of this species. Conclusions Cooper\u27s Hawks, Red-tailed Hawks, and American Kestrels use both regular and translational head movements, but to different extents. We conclude that these diurnal raptors have species-specific strategies to gather visual information while perching. These strategies may optimize prey search and detection with different visual systems in habitat types with different degrees of visual obstruction

The Boston Puerto Rican Health Study, a longitudinal cohort study on health disparities in Puerto Rican adults: challenges and opportunities

BACKGROUND: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support. METHODS: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up. RESULTS: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%). CONCLUSIONS: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities