Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Patient Complexity: More Than Comorbidity. The Vector Model of Complexity

BACKGROUND: The conceptualization of patient complexity is just beginning in clinical medicine. OBJECTIVES: This study aims (1) to propose a conceptual approach to complex patients; (2) to demonstrate how this approach promotes achieving congruence between patient and provider, a critical step in the development of maximally effective treatment plans; and (3) to examine availability of evidence to guide trade-off decisions and assess healthcare quality for complex patients. METHODS/RESULTS: The Vector Model of Complexity portrays interactions between biological, socioeconomic, cultural, environmental and behavioral forces as health determinants. These forces are not easily discerned but exert profound influences on processes and outcomes of care for chronic medical conditions. Achieving congruence between patient, physician, and healthcare system is essential for effective, patient-centered care; requires assessment of all axes of the Vector Model; and, frequently, requires trade-off decisions to develop a tailored treatment plan. Most evidence-based guidelines rarely provide guidance for trade-off decisions. Quality measures often exclude complex patients and are not designed explicitly to assess their overall healthcare. CONCLUSIONS/RECOMMENDATIONS: We urgently need to expand the evidence base to inform the care of complex patients of all kinds, especially for the clinical trade-off decisions that are central to tailoring care. We offer long- and short-term strategies to begin to incorporate complexity into quality measurement and performance profiling, guided by the Vector Model. Interdisciplinary research should lay the foundation for a deeper understanding of the multiple sources of patient complexity and their interactions, and how provision of healthcare should be harmonized with complexity to optimize health

Neogenin May Functionally Substitute for Dcc in Chicken

Dcc is the key receptor that mediates attractive responses of axonal growth cones to netrins, a family of axon guidance cues used throughout evolution. However, a Dcc homolog has not yet been identified in the chicken genome, raising the possibility that Dcc is not present in avians. Here we show that the closely related family member neogenin may functionally substitute for Dcc in the developing chicken spinal cord. The expression pattern of chicken neogenin in the developing spinal cord is a composite of the distribution patterns of both rodent Dcc and neogenin. Moreover, whereas the loss of mouse neogenin has no effect on the trajectory of commissural axons, removing chicken neogenin by RNA interference results in a phenotype similar to the functional inactivation of Dcc in mouse. Taken together, these data suggest that the chick neogenin is functionally equivalent to rodent Dcc

Transplantation of Specific Human Astrocytes Promotes Functional Recovery after Spinal Cord Injury

Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human astrocytes that appears to be particularly suitable for further development towards clinical application in treating the traumatically injured or diseased human central nervous system

An interdisciplinary team communication framework and its application to healthcare 'e-teams' systems design

<p>Abstract</p> <p>Background</p> <p>There are few studies that examine the processes that interdisciplinary teams engage in and how we can design health information systems (HIS) to support those team processes. This was an exploratory study with two purposes: (1) To develop a framework for interdisciplinary team communication based on structures, processes and outcomes that were identified as having occurred during weekly team meetings. (2) To use the framework to guide 'e-teams' HIS design to support interdisciplinary team meeting communication.</p> <p>Methods</p> <p>An ethnographic approach was used to collect data on two interdisciplinary teams. Qualitative content analysis was used to analyze the data according to structures, processes and outcomes.</p> <p>Results</p> <p>We present details for team meta-concepts of structures, processes and outcomes and the concepts and sub concepts within each meta-concept. We also provide an exploratory framework for interdisciplinary team communication and describe how the framework can guide HIS design to support 'e-teams'.</p> <p>Conclusion</p> <p>The structures, processes and outcomes that describe interdisciplinary teams are complex and often occur in a non-linear fashion. Electronic data support, process facilitation and team video conferencing are three HIS tools that can enhance team function.</p

AB-QTL analysis in winter wheat: II. Genetic analysis of seedling and field resistance against leaf rust in a wheat advanced backcross population

The present study aimed to localize exotic quantitative trait locus (QTL) alleles for the improvement of leaf rust (P.triticina) resistance in an advanced backcross (AB) population, B22, which is derived from a cross between the winter wheat cultivar Batis (Triticumaestivum) and the synthetic wheat accession Syn022L. The latter was developed from hybridization of T.turgidum ssp. dicoccoides and T.tauschii. Altogether, 250 BC2F3 lines of B22 were assessed for seedling resistance against the leaf rust isolate 77WxR under controlled conditions. In addition, field resistance against leaf rust was evaluated by assessing symptom severity under natural infestation across multiple environments. Simultaneously, population B22 was genotyped with a total of 97 SSR markers, distributed over the wheat A, B and D genomes. The phenotype and genotype data were subjected to QTL analysis by applying a 3-factorial mixed model analysis of variance including the marker genotype as a fixed effect and the environments, the lines and the marker by environment interactions as random effects. The QTL analysis revealed six putative QTLs for seedling resistance and seven for field resistance. For seedling resistance, the effects of exotic QTL alleles improved resistance at all detected loci. The maximum decrease of disease symptoms (−46.3%) was associated with marker locus Xbarc149 on chromosome 1D. For field resistance, two loci had stable main effects across environments and five loci exhibited marker by environment interaction effects. The strongest effects were detected at marker locus Xbarc149 on chromosome 1D, at which the exotic allele decreased seedling symptoms by 46.3% and field symptoms by 43.6%, respectively. Some of the detected QTLs co-localized with known resistance genes, while others appear to be as novel resistance loci. Our findings indicate, that the exotic wheat accession Syn022L may be useful for the improvement of leaf rust resistance in cultivated wheat

N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans

To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO2, equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans

Oxygenated-Blood Colour Change Thresholds for Perceived Facial Redness, Health, and Attractiveness

Blood oxygenation level is associated with cardiovascular fitness, and raising oxygenated blood colouration in human faces increases perceived health. The current study used a two-alternative forced choice (2AFC) psychophysics design to quantify the oxygenated blood colour (redness) change threshold required to affect perception of facial colour, health and attractiveness. Detection thresholds for colour judgments were lower than those for health and attractiveness, which did not differ. The results suggest redness preferences do not reflect a sensory bias, rather preferences may be based on accurate indications of health status. Furthermore, results suggest perceived health and attractiveness may be perceptually equivalent when they are assessed based on facial redness. Appearance-based motivation for lifestyle change can be effective; thus future studies could assess the degree to which cardiovascular fitness increases face redness and could quantify changes in aerobic exercise needed to increase facial attractiveness

The devil is in the details: trends in avoidable hospitalization rates by geography in British Columbia, 1990–2000

BACKGROUND: Researchers and policy makers have focussed on the development of indicators to help monitor the success of regionalization, primary care reform and other health sector restructuring initiatives. Certain indicators are useful in examining issues of equity in service provision, especially among older populations, regardless of where they live. AHRs are used as an indicator of primary care system efficiency and thus reveal information about access to general practitioners. The purpose of this paper is to examine trends in avoidable hospitalization rates (AHRs) during a period of time characterized by several waves of health sector restructuring and regionalization in British Columbia. AHRs are examined in relation to non-avoidable and total hospitalization rates as well as by urban and rural geography across the province. METHODS: Analyses draw on linked administrative health data from the province of British Columbia for 1990 through 2000 for the population aged 50 and over. Joinpoint regression analyses and t-tests are used to detect and describe trends in the data. RESULTS: Generally speaking, non-avoidable hospitalizations constitute the vast majority of hospitalizations in a given year (i.e. around 95%) with AHRs constituting the remaining 5% of hospitalizations. Comparing rural areas and urban areas reveals that standardized rates of avoidable, non-avoidable and total hospitalizations are consistently higher in rural areas. Joinpoint regression results show significantly decreasing trends overall; lines are parallel in the case of avoidable hospitalizations, and lines are diverging for non-avoidable and total hospitalizations, with the gap between rural and urban areas being wider at the end of the time interval than at the beginning. CONCLUSION: These data suggest that access to effective primary care in rural communities remains problematic in BC given that rural areas did not make any gains in AHRs relative to urban areas under recent health sector restructuring initiatives. It remains important to continue to monitor the discrepancy between them as a reflection of inequity in service provision. In addition, it is important to consider alternative explanations for the observed trends paying particular attention to the needs of rural and urban populations and the factors influencing local service provision