Immunocytochemical localization of the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase to postsynaptic structures in the rat brain.

The cellular and subcellular distribution of a major cyclic AMP binding protein in the central nervous system, the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase (RII-B), was analyzed in rat brains with light and electron microscopic immunocytochemical methods. The distribution of the non-neural isoform of the regulatory subunit of the enzyme (RII-H) was also analyzed. It was found that RII-B immunoreactivity was predominantly localized to neurons whereas glial and endothelial cells were unlabeled. In the neurons the RII-B immunoreactivity occurred in the perikaryal cytoplasm and in the dendrites; there was no significant accumulation of immunoreaction product in nuclei, myelinated axons and axon terminals. Although immunoreactivity was never detected in axon terminals, it was characteristically associated with the postsynaptic densities and the surrounding non-synaptic sites in somata, dendrites and dendritic spines. The localization of RII-B antigenic sites did not show specificity to any type of neuron or synapse, but the amount of immunoreactivity varied. The distribution of RII-H immunoreactivity was similar to that of RII-B except that RII-H immunoreaction product was also observed in glial cells and occurred more frequently in myelinated axons. Our data confirm that RII-B is one of the major cyclic AMP binding proteins in neurons, and provide morphological support for the involvement of the type II cyclic AMP-dependent protein kinase in postsynaptic neural functions

Comparing orbiter and rover image-based mapping of an ancient sedimentary environment, Aeolis Palus, Gale crater, Mars

This study provides the first systematic comparison of orbital facies maps with detailed ground-based geology observations from the Mars Science Laboratory (MSL) Curiosity rover to examine the validity of geologic interpretations derived from orbital image data. Orbital facies maps were constructed for the Darwin, Cooperstown, and Kimberley waypoints visited by the Curiosity rover using High Resolution Imaging Science Experiment (HiRISE) images. These maps, which represent the most detailed orbital analysis of these areas to date, were compared with rover image-based geologic maps and stratigraphic columns derived from Curiosity's Mast Camera (Mastcam) and Mars Hand Lens Imager (MAHLI). Results show that bedrock outcrops can generally be distinguished from unconsolidated surficial deposits in high-resolution orbital images and that orbital facies mapping can be used to recognize geologic contacts between well-exposed bedrock units. However, process-based interpretations derived from orbital image mapping are difficult to infer without known regional context or observable paleogeomorphic indicators, and layer-cake models of stratigraphy derived from orbital maps oversimplify depositional relationships as revealed from a rover perspective. This study also shows that fine-scale orbital image-based mapping of current and future Mars landing sites is essential for optimizing the efficiency and science return of rover surface operations

Complementary classifications of aeolian dunes based on morphology, dynamics, and fluid mechanics

Dunes form where winds blow over a bed of mobile sediment grains – conditions that are common in our solar system. On Earth, dunes abound in arid continental interiors and along sandy coastlines. Dune fields have also been recognized on Venus, Mars, Saturn's moon Titan, and Pluto. In response to the different boundary conditions and other environmental forcings, dunes adopt a rich diversity of shapes, sizes, and behaviors. Thus, people around the globe and over centuries have developed a rich vocabulary to describe dunes and their complexity. As a result, existing dune nomenclature often includes redundant terms with differing definitions across scientific communities. Previous studies have endeavored to link dune shape to environmental forcing, usually by means of correlation. Although instructive, correlation-based classifications can be misleading if not based on an underlying mechanics and if dune morphogenetic classes are not uniquely defined. Here, we synthesize existing dune terminology and use the last two decades of research on dune morphodynamics to propose three complementary dune classification schemes based on: (1) descriptive dune gemorphology, (2) morphodynamic processes, and (3) fluid mechanics and physics of sediment transport. The first classification relates dune types to geomorphic setting, presence or absence of vegetation or obstacles, and dune shape (including planform shape, and cross-sectional symmetry or asymmetry). Dune classes can be further subdivided where the direction of sand transport is known independently. The second classification relates dune types and shapes to bed properties (sand-covered vs partially starved bed) and wind forcing (directional variability or the relative strengths and directions of wind modes) that together influence dune dynamics (growth, migration, elongation) and select the dominant processes by which dunes are shaped and oriented relative to the resultant transport direction. The third classification relates, for different planetary environments, the range of possible dune sizes, from minimum to maximum wavelength, to flow regime (rough or smooth) and response of sediment transport, which influence the coupling between sand bed topography, fluid flow, and sediment transport. These characteristic lengths are useful scales for comparative geomorphology. The three classification schemes provide complementary information. Together, they form a unified framework for geomorphologists, sedimentologists, geographers, physicists, and others to describe windblown sand dunes on Earth and beyond through their shape, dynamics, and size as a response to winds and boundary conditions

Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control

Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the `resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistanceassociated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised

Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public

<p>Abstract</p> <p>Background</p> <p>During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1) among the Saudi public.</p> <p>Methods</p> <p>A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic.</p> <p>Results</p> <p>More than half (54.3%, 840/1548) of the participants showed high concern, 43.7%(677/1548) showed a low level of knowledge, and 60.8%(941/1548) had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p < 0.001), while greater precautionary measures were taken by participants who were male (p < 0.001), older (p = 0.047), better educated (p = 0.04), and more knowledgeable (p < 0.001). More than one-third (38.3%) of participants were not convinced that the MOH reports about the disease were true, and only 16.1% of the participants reported receiving information from health providers.</p> <p>Conclusions</p> <p>High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.</p

Genome-wide compendium and functional assessment of in vivo heart enhancers

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function

Your space or mine? : Mapping self in time

Peer reviewedPublisher PD

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

Health-related quality of life in diabetic patients and controls without diabetes in refugee camps in the Gaza strip: a cross-sectional study

BACKGROUND: Prevalence of diabetes mellitus is increasing in developed and developing countries. Diabetes is known to strongly affect the health-related quality of life (HRQOL). HRQOL is also influenced by living conditions. We analysed the effects of having diabetes on HRQOL under the living conditions in refugee camps in the Gaza strip. METHODS: We studied a sample of 197 diabetic patients who were recruited from three refugee camps in the Gaza strip and 197 age- and sex-matched controls living in the same camps. To assess HRQOL, we used the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) including four domains (physical health, psychological, social relations and environment). Domain scores were compared for cases (diabetic patients) and controls (persons without diabetes) and the impact of socio-economic factors was evaluated in both groups. RESULTS: All domains were strongly reduced in diabetic patients as compared to controls, with stronger effects in physical health (36.7 vs. 75.9 points of the 0–100 score) and psychological domains (34.8 vs. 70.0) and weaker effects in social relationships (52.4 vs. 71.4) and environment domains (23.4 vs. 36.2). The impact of diabetes on HRQOL was especially severe among females and older subjects (above 50 years). Low socioeconomic status had a strong negative impact on HRQOL in the younger age group (<50 years). CONCLUSION: HRQOL is strongly reduced in diabetic patients living in refugee camps in the Gaza strip. Women and older patients are especially affected