Protein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few ...residues near the phospho-acceptor residue, forming the so-called kinase-substrate motif. Kinases have been extensively duplicated throughout evolution, but little is known about when in time new target motifs have arisen. Here, we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity-determining residues. We then analysed kinase specificity models, based on known target sites, observing that specificity has remained mostly unchanged for recent kinase duplications. Finally, analysis of phosphorylation data from a taxonomically broad set of 48 eukaryotic species indicates that most phosphorylation motifs are broadly distributed in eukaryotes but are not present in prokaryotes. Overall, our results suggest that the set of eukaryotes kinase motifs present today was acquired around the time of the eukaryotic last common ancestor and that early expansions of the protein kinase fold rapidly explored the space of possible target motifs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Six main alternative linkage proposals which involve the Sino-Tibetan family, including Sinitic and other language families of the East Asian area (Miao-Yao, Altaic/Transeurasian, Austroasiatic, ...Tai-Kadai, Austronesian) are briefly outlined. Using the standard techniques of comparative linguistics, a remote linkage between the Sino-Tibetan languages, including Sinitic, the Yeniseian languages of Siberia, and the Na-Dene languages of northwest North America is demonstrated. This includes cognate core lexicon showing regular sound correspondences, morphological similarities of form and function, as well as similarities in social structure. The other proposals for linkages that connect Sinitic and other languages of the East Asian area appear not to be based on a genetic linguistic relationship but rather due to contact: millennia of loanwords from Sinitic into the languages of those families and some lexicon borrowed into Sinitic. More remains to be done to further document the status of the linkage between Sino-Tibetan and Dene-Yeniseian.
Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; ...yet, obesity also independently heightens risk of Alzheimer’s Disease (AD), even after adjusting for other important confounding risk factors including blood pressure, sociodemographics, cholesterol levels, smoking status, and Apolipoprotein E (ApoE) genotype. Among patients over the age of 65 with dementia, 37% have coexisting diabetes, and an estimated 7.3% of cases of AD are directly attributable to midlife obesity. Clusterin, also known as apolipoprotein J (ApoJ), is a multifunctional glycoprotein that acts as a molecular chaperone, assisting folding of secreted proteins. Clusterin has been implicated in several physiological and pathological states, including AD, metabolic disease, and cardiovascular disease. Despite long-standing interest in elucidating clusterin’s relationship with amyloid beta (Aβ) aggregation/clearance and toxicity, significant knowledge gaps still exist. Altered clusterin expression and protein levels have been linked with cognitive and memory function, disrupted central nervous system lipid flux, as well as pathogenic brain structure; and its role in cardiometabolic disease suggests that it may be a link between insulin resistance, dyslipidemia, and AD. Here, we briefly highlight clusterin’s relevance to AD by presenting existing evidence linking clusterin to AD and cardiometabolic disease, and discussing its potential utility as a biomarker for AD in the presence of obesity-related metabolic disease.
Abstract
High-resolution vision requires fine retinal sampling followed by integration to recover object properties. Importantly, accuracy is lost if local samples from different objects are ...intermixed. Thus, segmentation, grouping of image regions for separate processing, is crucial for perception. Previous work has used bi-stable plaid patterns, which can be perceived as either a single or multiple moving surfaces, to study this process. Here, we report a relationship between activity in a mid-level site in the primate visual pathways and segmentation judgments. Specifically, we find that direction selective middle temporal neurons are sensitive to texturing cues used to bias the perception of bi-stable plaids and exhibit a significant trial-by-trial correlation with subjective perception of a constant stimulus. This correlation is greater in units that signal global motion in patterns with multiple local orientations. Thus, we conclude the middle temporal area contains a signal for segmenting complex scenes into constituent objects and surfaces.
We estimate the lifetime attributable risk (LAR) of lung cancer incidence in symptomatic Coronary Artery Disease (CAD) patients receiving enhanced Coronary Computed Tomography Angiography (CCTA) and ...the unenhanced Computed Tomography Calcium Scoring (CTCS) examination. Retrospective analysis has been made of CCTA and CTCS data collected for 87 confirmed CAD adult patients. Patient effective dose (E) and organ doses (ODs) were calculated using CT-EXPO. Statistical correlation and the differences between E and ODs in enhanced CCTA and unenhanced CTCS were calculated using the Pearson coefficient and Wilcoxon unpaired t-test. Following BEIR VII report guidance, organ-specific LARs for the cohort were estimated using the organ-equivalent dose-to-risk conversion factor for numbers of cases per 100,000 patients exposed to low doses of 0.1 Gy. Significant statistical difference (p<0.0001) is found between E obtained for CTCS and that of CCTA. The scan length was found to be greater in CCTA (17.5 ± 2.9 cm) compared to that for CTCS (15 ± 2 cm). More elevated values of dose were noted for the esophagus (4.2 ± 2.15 mSv) and thymus (9.6 ± 2.54 mSv) for both CTCS and CCTA. CTCS organ doses were lower than that of CCTA. Per 100,000 patients, female cumulative doses are seen to give rise to greater lung cancer LARs compared to that for males, albeit with risk varying significantly, noticeably greater for females, younger patients and combined CCTA and CTCS scans. While scan parameters and tube-modulation methods clearly contribute to patient dose, mAs offers by far the greater contribution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular ...disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.
Protection of personnel against ionising exposure is necessary to prevent occurrence of biological risks. The objective of this study is to arranged light and heavy nuclei at the surface state ...particle of composite geopolymer concrete when filler with metal (Ni or Fe) for X-ray shielding applications. The composite fly ash geopolymer concrete with fillers Ni and fly ash geopolymer concrete with Fe as a shield for X-ray radiation has been successfully synthesized by a simple method. The shielding composites were carried out using Fourier transform infra-red (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and X-ray mobile to determine optical properties, structural properties, surface morphology, and shielding performance. In this study shows strong linear correlation between structural properties and the effectiveness of X-ray shielding. The best composite as an X-ray radiation shield is composite concrete geopolymer with AC and Ni as a filler indicated by higher linear attenuation coefficient
μ
due to present combination between heavy and light nuclei at the surface state of particle, consequently, produce high stability structural and optical properties, and bonding characteristics. The results in this study indicated composite concrete geopolymer fly ash with AC and Ni as a filler with sharp nodule at the surface state looks like prickly ball as a new composite for X-ray shield.
The small visual area known as MT or V5 has played a major role in our understanding of the primate cerebral cortex. This area has been historically important in the concept of cortical processing ...streams and the idea that different visual areas constitute highly specialized representations of visual information. MT has also proven to be a fertile culture dish--full of direction- and disparity-selective neurons--exploited by many labs to study the neural circuits underlying computations of motion and depth and to examine the relationship between neural activity and perception. Here we attempt a synthetic overview of the rich literature on MT with the goal of answering the question, What does MT do?
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Computed tomography (CT) derived Monte Carlo (MC) phantoms allow dose determination within small animal models that is not feasible with in-vivo dosimetry. The aim of this study was to develop a ...CT-derived MC phantom generated from a mouse with a xenograft tumour that could then be used to calculate both the dose heterogeneity in the tumour volume and out of field scattered dose for pre-clinical small animal irradiation experiments. A BEAMnrc Monte-Carlo model has been built of our irradiation system that comprises a lead collimator with a 1 cm diameter aperture fitted to a Cs-137 gamma irradiator. The MC model of the irradiation system was validated by comparing the calculated dose results with dosimetric film measurement in a polymethyl methacrylate (PMMA) phantom using a 1D gamma-index analysis. Dose distributions in the MC mouse phantom were calculated and visualized on the CT-image data. Dose volume histograms (DVHs) were generated for the tumour and organs at risk (OARs). The effect of the xenographic tumour volume on the scattered out of field dose was also investigated. The defined gamma index analysis criteria were met, indicating that our MC simulation is a valid model for MC mouse phantom dose calculations. MC dose calculations showed a maximum out of field dose to the mouse of 7% of Dmax. Absorbed dose to the tumour varies in the range 60%-100% of Dmax. DVH analysis demonstrated that tumour received an inhomogeneous dose of 12 Gy-20 Gy (for 20 Gy prescribed dose) while out of field doses to all OARs were minimized (1.29 Gy-1.38 Gy). Variation of the xenographic tumour volume exhibited no significant effect on the out of field scattered dose to OARs. The CT derived MC mouse model presented here is a useful tool for tumour dose verifications as well as investigating the doses to normal tissue (in out of field) for preclinical radiobiological research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
10.
Oxymetazoline for Ptosis Bradley, Elizabeth A; Bradley, David J
JAMA ophthalmology,
11/2020, Letnik:
138, Številka:
11
Journal Article
PDF
