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© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Transcription factors (TFs) control the rate of mRNA production. Technological advances have made the task of measuring mRNA levels for all genes straightforward, but identifying causal relationships between TFs and their target genes remains an unsolved problem in biology. In their recent study, McIsaac and colleagues (Hackett et al, 2020) apply a method for inducing the overexpression of a TF and studying the dynamics with which all transcripts respond. Using time series analysis, they are able to resolve direct effects of TFs from secondary effects. This new experimental and analytical approach provides an efficient means of defining gene regulatory relationships for all TFs. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Many clinical trials for cancer precision medicine have yielded unsatisfactory results due to challenges such as drug resistance and low efficacy. Drug resistance is often caused by the complex compensatory regulation within the biomolecular network in a cancer cell. Recently, systems biological studies have modeled and simulated such complex networks to unravel the hidden mechanisms of drug resistance and identify promising new drug targets or combinatorial or sequential treatments for overcoming resistance to anticancer drugs. However, many of the identified targets or treatments present major difficulties for drug development and clinical application. Nanocarriers represent a path forward for developing therapies with these "undruggable" targets or those that require precise combinatorial or sequential application, for which conventional drug delivery mechanisms are unsuitable. Conversely, a challenge in nanomedicine has been low efficacy due to heterogeneity of cancers in patients. This problem can also be resolved through systems biological approaches by identifying personalized targets for individual patients or promoting the drug responses. Therefore, integration of systems biology and nanomaterial engineering will enable the clinical application of cancer precision medicine to overcome both drug resistance of conventional treatments and low efficacy of nanomedicine due to patient heterogeneity. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Diabetic Ketoacidosis (DKA) is an acute metabolic condition, sometimes requiring admission to an Intensive Care Unit (ICU). AIMS To investigate the outcomes of DKA patients admitted to a hospital with restricted ICU capacity. METHODS We included all DKA patients above age 18 who were admitted to a tertiary hospital during 2004-2017. We conducted multivariate logistic regression analysis adjusted for ICU bed availability to analyze parameters associated with ICU admission, and a composite outcome of mortality, DKA recurrence and mechanical ventilation. RESULTS Among 382 DKA patients in our cohort, 94 (24.6%) were admitted to the ICU. The in-hospital mortality was 4.7%. Low bicarbonate ( less then 10 mmoL/L) and pH ( less then 7) levels at presentation were associated with ICU admission (p less then 0.001 for both). Tofacitinib JAK inhibitor In multi-variate models availability of beds in the ICU was not associated with ICU admission, mortality or DKA recurrence of any type. CONCLUSION In a setting of limited ICU capacity, DKA treatment does not necessarily require admission to the ICU. When the rising rates of diabetes mellitus and the associated elevated rates of DKA are taken into account, our results highlight the importance of including step-down units when devising local protocols for care of these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Cation-π interactions are common in nature, especially in organisms. Their profound influences in chemistry, physics, and biology have been continuously investigated since they were discovered in 1981. However, the importance of cation-π interactions in materials science, regarding carbonaceous nanomaterials, has just been realized. The interplay between cations and delocalized polarizable π electrons of graphene would bring about significant changes to the intrinsic characteristics of graphene and greatly affect the device performance based on graphene and its derivatives. Here, the cation-π interactions in graphene containing systems for water treatment applications (e.g., separation membranes, adsorbents) are highlighted. The cross-linking effects caused by cation-π interactions contribute to membrane stability and selectivity and enhanced adsorption. Their roles in dominating the performance of graphene-based structures for other specific applications are also discussed. Relevant theoretical modeling and calculations are summarized to offer an in-depth understanding of the underlying mechanisms which can help in designing more functional materials and structures. Perspectives on the potential directions that deserve effort are also presented. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.PURPOSE Although anorexia nervosa is classified as a psychiatric disorder associated with socio-environmental and psychological factors, a deeper insight into the dominant neurobiological basis is needed to develop a more effective approach of treatment. Given the high contribution of genetic predisposition and the underlying pathophysiology of neurohormonal circuits, it seems that pharmacological targeting of these mechanisms may provide us with better therapeutic outcomes. METHODS 1 H-NMR spectroscopy was used to measure concentrations of the hypothalamus and brain stem metabolites in an activity-based rodent model (ABA) after subcutaneous administration of kisspeptin-10. Because anorexia mainly affects young women and often leads to hypogonadotropic-hypogonadism, we investigated the influence of this neuropeptide, which is involved in reproductive function by regulating the hypothalamic-pituitary-gonadal axis, on the ABA model development. RESULTS Kisspeptin reinforced food consumption in an activity-based rodent model of anorexia changing a pattern of weight loss. 1 H-NMR spectroscopy of the hypothalamus and brain stem of ABA rats revealed a statistically significant change in the concentration of creatine (Cr; decreased, P = 0.030), phosphocreatine (PCr; increased, P = 0.030), γ-aminobutyric acid (GABA; decreased, P = 0.011), glutathione (GSH; increased, P = 0.011) and inositol (INS; increased, P = 0.047) compared to the control group. Subcutaneous administration of kisspeptin reversed the decrease in GABA (P = 0.018) and Cr (P = 0.030) levels in the hypothalamus as well as restored glutamate (GLU; P = 0.040) level in the brain stem. CONCLUSIONS We suspect that kisspeptin through modulation of hypothalamic GABAergic signaling increases food intake, and thus positively alters brain metabolism. © 2020 John Wiley & Sons, Ltd.
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