Lipoprotein(a) — A Hallmark in Atherosclerosis and Cardiovascular Diseases

Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein (LDL)-like core and apo(a), a large molecular weight glycoprotein. Apo(a) is highly homologous to plasminogen, yet in contrast exhibits a unique size polymorphism that is characterized by an increasing number of kringle-IV (K-IV) repeats. The number of K-IV repeats ranges from n = 2 to n = 40 or even higher. Apo(a) is synthesized almost exclusively in the liver and there is still some debate whether the assembly of Lp(a) from LDL and apo(a) occurs inside the liver cells or in the circulating blood. The plasma Lp(a) concentration is markedly skewed reaching from 200 mg/dl. The plasma concentration is >90% genetically determined and correlates negatively with the number of K-IV repeats. In the apo(a) promoter, there are numerous response elements for transcription factors and nuclear receptors that regulate apo(a) expression. The HNF4α binding sequence appears to be the most important one in that respect, yet further work needs to be done to unravel the key features of apo(a) biosynthesis under different conditions. Importantly, activation of FXR causes the dissociation of HNF4α α from its response element and in turn a significant downregulation of apo(a) transcription

A Rare Case Series of Ischemic Stroke Following Russell’s Viper Snake Bite in India

Snakebite is an important medical problem in India. Among their various manifestations, cerebral complications are uncommonly found in literature. Moreover, Ischemic stroke following snake bite is quite rare. Here we report a case series of two such cases that developed neurological manifestations following Russell’s viper bite. On computerized tomography (CT) scan of brain; cerebral infarcts were revealed. Their likely mechanisms are discussed in present study which include disseminated intravascular coagulation, toxin induced vasculitis and endothelial damage

A PIONEERING SCAFFOLD FOR EMPLOY REINFORCE SLAB MIXTURE

Within this project, we view and studied completely some utilizes a site associated with publish tensioned slabs. The different sizes of tendons available, what are materials imparting prestress towards the structure were studied completely. We've also understood and performed building column line staking on-site. The tendons are specified by the forms in compliance with installation sketches that indicate the way they should be spaced, what their profile ought to be where they should be stressed. Following the concrete is positioned and it has arrived at its needed strength, usually about 75% of their final strength, then your prestressing process begins. The key is the fact that once the tendons are extended, want revisit their original length but they are avoided from doing this through the anchorages. The truth that the tendons are stored inside a permanently stressed condition leads to a compressive pressure to do something around the concrete. This considerably boosts the load-transporting capacity from the concrete. Since publish-tensioned concrete is cast in position in the job site, there's very little limit towards the shapes that may be created. Curved facades, arches and complex slab edge layouts are frequently a trademark of publish-tensioned concrete structures. Publish tensioning is just evolving increasingly more with growing innovation of creative and atmosphere friendly materials. An essential aspect to become stored in your mind may be the sustainability. Publish tensioned concrete has a lot of advantages in comparison with conventional RCC construction, probably the most important to be the decrease in self weight and overall decrease in the advantages of materials

ASSOCIATING COMMUNAL TELEVISION: A MICRO BLOGGING RECOMMENDER SYSTEM

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Treatment of Urethral Strictures from Irradiation and Other Nonsurgical Forms of Pelvic Cancer Treatment

Radiation therapy (RT), external beam radiation therapy (EBRT), brachytherapy (BT), photon beam therapy (PBT), high intensity focused ultrasound (HIFU), and cryotherapy are noninvasive treatment options for pelvic malignancies and prostate cancer. Though effective in treating cancer, urethral stricture disease is an underrecognized and poorly reported sequela of these treatment modalities. Studies estimate the incidence of stricture from BT to be 1.8%, EBRT 1.7%, combined EBRT and BT 5.2%, and cryotherapy 2.5%. Radiation effects on the genitourinary system can manifest early or months to years after treatment with the onus being on the clinician to investigate and rule-out stricture disease as an underlying etiology for lower urinary tract symptoms. Obliterative endarteritis resulting in ischemia and fibrosis of the irradiated tissue complicates treatment strategies, which include urethral dilation, direct-vision internal urethrotomy (DVIU), urethral stents, and urethroplasty. Failure rates for dilation and DVIU are exceedingly high with several studies indicating that urethroplasty is the most definitive and durable treatment modality for patients with radiation-induced stricture disease. However, a detailed discussion should be offered regarding development or worsening of incontinence after treatment with urethroplasty. Further studies are required to assess the nature and treatment of cryotherapy and HIFU-induced strictures

Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice

SummaryWe recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation. These effects were consistent in 3T3-L1 adipocytes, C2C12 myoblasts, and in tissues from Nat1-deficient mice, including white adipose tissue, heart, and skeletal muscle. Nat1-deficient mice had changes in plasma metabolites and lipids consistent with a decreased ability to utilize fats for energy and a decrease in basal metabolic rate and exercise capacity without altered thermogenesis. Collectively, our results suggest that Nat1 deficiency results in mitochondrial dysfunction, which may constitute a mechanistic link between this gene and IR

Prots: A fragment based protein thermo‐stability potential

Designing proteins with enhanced thermo‐stability has been a main focus of protein engineering because of its theoretical and practical significance. Despite extensive studies in the past years, a general strategy for stabilizing proteins still remains elusive. Thus effective and robust computational algorithms for designing thermo‐stable proteins are in critical demand. Here we report PROTS, a sequential and structural four‐residue fragment based protein thermo‐stability potential. PROTS is derived from a nonredundant representative collection of thousands of thermophilic and mesophilic protein structures and a large set of point mutations with experimentally determined changes of melting temperatures. To the best of our knowledge, PROTS is the first protein stability predictor based on integrated analysis and mining of these two types of data. Besides conventional cross validation and blind testing, we introduce hypothetical reverse mutations as a means of testing the robustness of protein thermo‐stability predictors. In all tests, PROTS demonstrates the ability to reliably predict mutation induced thermo‐stability changes as well as classify thermophilic and mesophilic proteins. In addition, this white‐box predictor allows easy interpretation of the factors that influence mutation induced protein stability changes at the residue level. Proteins 2012; © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89526/1/23163_ftp.pd

Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo

Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe the development of a structural proteomics approach to identify the amino acids responsible for aberrant self-association of monoclonal antibodies and the design of a variant with reduced aggregation and increased serum persistence in vivo. We show that the human monoclonal antibody, MEDI1912, selected against nerve growth factor binds with picomolar affinity, but undergoes reversible self-association and has a poor pharmacokinetic profile in both rat and cynomolgus monkeys. Using hydrogen/deuterium exchange and cross-linking-mass spectrometry we map the residues responsible for self-association of MEDI1912 and show that disruption of the self-interaction interface by three mutations enhances its biophysical properties and serum persistence, whilst maintaining high affinity and potency. Immunohistochemistry suggests that this is achieved via reduction of non-specific tissue binding. The strategy developed represents a powerful and generic approach to improve the properties of therapeutic proteins