89 research outputs found
The cuticle modulates ultraviolet reflectance of avian eggshells
ABSTRACT Avian eggshells are variedly coloured, yet only two pigments, biliverdin and protoporphyrin IX, are known to contribute to the dramatic diversity of their colours. By contrast, the contributions of structural or other chemical components of the eggshell are poorly understood. For example, unpigmented eggshells, which appear white to the human eye, vary in their ultraviolet (UV) reflectance, which may be detectable by birds. We investigated the proximate mechanisms for the variation in UV-reflectance of unpigmented bird eggshells using spectrophotometry, electron microscopy, chemical analyses, and experimental manipulations. We specifically tested how UV-reflectance is affected by the eggshell cuticle, the outermost layer of most avian eggshells. The chemical dissolution of the outer eggshell layers, including the cuticle, increased UV-reflectance for only eggshells that contained a cuticle. Our findings demonstrate that the outer eggshell layers, including the cuticle, absorb UV-light, probably because they contain higher levels of organic components and other chemicals, such as calcium phosphates, compared to the predominantly calcite-based eggshell matrix. These data highlight the need to examine factors other than the known pigments in studies of avian eggshell colour
Socioeconomic Differences in the Effectiveness of the Removal of the “Light” Descriptor on Cigarette Packs: Findings from the International Tobacco Control (ITC) Thailand Survey
Many smokers incorrectly believe that “light” cigarettes are less harmful than regular cigarettes. To address this problem, many countries have banned “light” or “mild” brand descriptors on cigarette packs. Our objective was to assess whether beliefs about “light” cigarettes changed following the 2007 removal of these brand descriptors in Thailand and, if a change occurred, the extent to which it differed by socioeconomic status. Data were from waves 2 (2006), 3 (2008), and 4 (2009) of the International Tobacco Control (ITC) Thailand Survey of adult smokers in Thailand. The results showed that, following the introduction of the ban, there was an overall decline in the two beliefs that “light” cigarettes are less harmful and smoother than regular cigarettes. The decline in the “less harmful” belief was considerably steeper in lower income and education groups. However, there was no evidence that the rate of decline in the “smoother” belief varied by income or education. Removing the “light” brand descriptor from cigarette packs should thus be viewed not only as a means to address the problem of smokers’ incorrect beliefs about “light” cigarettes, but also as a factor that can potentially reduce socioeconomic disparities in smoking-related misconceptions
Cadherin-10 maintains excitatory/inhibitory ratio through interactions with synaptic proteins
Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded byCDH10within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENTThe correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism.</jats:p
How to do an evaluation: pitfalls and traps
The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used
How to do an evaluation: pitfalls and traps
The recent literature is replete with papers evaluating computational tools (often those operating on 3D structures) for their performance in a certain set of tasks. Most commonly these papers compare a number of docking tools for their performance in cognate re-docking (pose prediction) and/or virtual screening. Related papers have been published on ligand-based tools: pose prediction by conformer generators and virtual screening using a variety of ligand-based approaches. The reliability of these comparisons is critically affected by a number of factors usually ignored by the authors, including bias in the datasets used in virtual screening, the metrics used to assess performance in virtual screening and pose prediction and errors in crystal structures used
Gene Expression Patterns in Peripheral Blood Correlate with the Extent of Coronary Artery Disease
Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall
HIV-1 Envelope Subregion Length Variation during Disease Progression
The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic
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The Curing Coma Campaign: Framing Initial Scientific Challenges—Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting
Abstract: Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the “grand challenge” of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the “curing coma community” to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients
Purinergic signalling and immune cells
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells
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