Project description:Interferons (IFNs) possess broad-spectrum antiviral activity to resist virus epidemic. However, IFNs antiviral efficacy needs to be greatly improved. Here, we reveal that LATS1 is a vital signal transmitter governing full type-I-interferon (IFN-I) signaling activity. Importantly, LATS1 deficiency restricts IFN-I signaling and attenuates host antiviral immune response.
Project description:A full-field X-ray fluorescence imaging (FXI) station was recently developed at beamline BL8 of Synchrotron Light Research Institute (SLRI), Thailand. An unfocused, synchrotron X-ray beam from the bending magnet with a size of 2 mm (vertical) × 13 mm (horizontal) and photon energy of 10 keV was employed in the FXI experiments. A sample stage was tilted by 7.5° to enlarge the vertical beam size. X-ray fluorescence images were recorded by an energy-dispersive, 256 × 256 array, pn-type charge coupled device detector equipped with a polycapillary optics, providing a full-frame image size of 12.3 mm × 12.3 mm. The incident photon flux per pixel was 3 × 104 photons s-1 (100 mA)-1 and the experimental spatial resolution was 68 µm. Image processing was carried out offline using an in-house MATLAB program capable of elemental selection and inhomogeneity intensity correction. Elemental detection limits of FXI were found to decrease with increasing atomic number, i.e. 0.3 to 0.03 wt% for Z = 19 (K) to 30 (Zn). Compared with the BL6b microbeam imaging (µXI) station at SLRI with higher photon flux per pixel, 3 × 1010 photons s-1 (100 mA)-1, a tenfold sample area can be obtained and 13 times higher peak-to-background (PKB) ratio at Zn Kα measured with the same experimental time (8 h). Simultaneous measurement of FXI is more time-efficient against the long overhead times of µXI scanning over large pixel numbers, >65000. To demonstrate potential applications of the new FXI station, various types of samples were examined: dendritic limestone, ancient bronze and dried fish. Analyzed elemental images enabled us to identify areas rich in Mn on the limestone, Sn and Cu separation in the bronze, and Zn nutrition in the dried fish eye.
Project description:Many microbial agents have been implicated as contributors to cancer genesis and development, and the search to identify and characterize new cancer-related organisms is ongoing. Modern developments in methodologies, especially culture-independent approaches, have accelerated and driven this research. Recent work has shed light on the multifaceted role that the community of organisms in and on the human body plays in cancer onset, development, detection, treatment, and outcome. Much remains to be discovered, however, as methodological variation and functional testing of statistical correlations need to be addressed for the field to advance.
Project description:Interferons (IFNs) possess broad-spectrum antiviral activity to resist virus epidemic. However, IFNs antiviral efficacy needs to be greatly improved. Here, we reveal that LATS1 is a vital signal transmitter governing full type-I-interferon (IFN-I) signaling activity. Importantly, LATS1 deficiency restricts IFN-I signaling and attenuates host antiviral immune response.
Project description:Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.
Project description:The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.
Project description:Specimens and associated data in natural history collections (NHCs) foster substantial scientific progress. In this paper, we explore recent contributions of NHCs to the study of systematics and biogeography, genomics, morphology, stable isotope ecology, and parasites and pathogens of mammals. To begin to assess the magnitude and scope of these contributions, we analyzed publications in the Journal of Mammalogy over the last decade, as well as recent research supported by a single university mammal collection (Museum of Southwestern Biology, Division of Mammals). Using these datasets, we also identify weak links that may be hindering the development of crucial NHC infrastructure. Maintaining the vitality and growth of this foundation of mammalogy depends on broader engagement and support from across the scientific community and is both an ethical and scientific imperative given the rapidly changing environmental conditions on our planet.
Project description:Interferons (IFNs) have broad-spectrum antiviral activity to resist virus epidemic. However, IFN antiviral efficacy needs to be greatly improved. Here, we reveal that LATS1 is a vital signal transmitter governing full type-I IFN (IFN-I) signaling activity. LATS1 constitutively binds with the IFN-I receptor IFNAR2 and is rapidly tyro-phosphorylated by Tyk2 upon IFN-I engagement. Tyro-phosphorylation of LATS1 promotes LATS1 activation and YAP degradation, thereby promoting IFN-mediated antiproliferation activity. Moreover, activated LATS1 translocates into the nucleus and induces CDK8-Ser62 phosphorylation, which in turn phosphorylates STAT1 at Ser727 and induces full IFN-I antiviral activity. LATS1 deficiency restricts in vivo IFN-I signaling and attenuates host antiviral immune response. Our study identifies IFN-I as a previously unidentified extracellular diffusible ligand signal for activation of the Hippo core LATS1 pathway and reveals Tyk2-LATS1-CDK8 as a complete signaling cascade controlling full IFN-I activity.
Project description:Background and purposeThe Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.MethodsThis forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.ResultsThe imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.ConclusionsRecent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.
Project description:Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent research related to antiaging strategies and treatments. We review the recent advances and delineate trends in research headway of antiaging knowledge and practice across time, geography, and development pipelines. We further assess the state-of-the-art antiaging approaches and explore their correlations with age-related diseases. The landscape of antiaging drugs has been outlined and explored. Well-recognized and novel, currently evaluated antiaging agents have also been summarized. Finally, we review clinical applications of antiaging products with their development pipelines. The objective of this review is to summarize current knowledge on preventive strategies and treatment remedies in the field of aging, to outline challenges and evaluate growth opportunities, in order to further efforts to solve the problems that remain.