A Global Characterization and Identification of Multifunctional Enzymes

Multi-functional enzymes are enzymes that perform multiple physiological functions. Characterization and identification of multi-functional enzymes are critical for communication and cooperation between different functions and pathways within a complex cellular system or between cells. In present study, we collected literature-reported 6,799 multi-functional enzymes and systematically characterized them in structural, functional, and evolutionary aspects. It was found that four physiochemical properties, that is, charge, polarizability, hydrophobicity, and solvent accessibility, are important for characterization of multi-functional enzymes. Accordingly, a combinational model of support vector machine and random forest model was constructed, based on which 6,956 potential novel multi-functional enzymes were successfully identified from the ENZYME database. Moreover, it was observed that multi-functional enzymes are non-evenly distributed in species, and that Bacteria have relatively more multi-functional enzymes than Archaebacteria and Eukaryota. Comparative analysis indicated that the multi-functional enzymes experienced a fluctuation of gene gain and loss during the evolution from S. cerevisiae to H. sapiens. Further pathway analyses indicated that a majority of multi-functional enzymes were well preserved in catalyzing several essential cellular processes, for example, metabolisms of carbohydrates, nucleotides, and amino acids. What’s more, a database of known multi-functional enzymes and a server for novel multi-functional enzyme prediction were also constructed for free access at http://bioinf.xmu.edu.cn/databases/MFEs/index.htm

Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3

Uphold the nuclear weapons test moratorium

The Trump administration is considering renewing nuclear weapons testing (1), a move that could increase the risk of another nuclear arms race as well as an inadvertent or intentional nuclear war. Following in the long tradition of scientists opposing nuclear weapons due to their harmful effects on both humanity and the planet (2), we ask the U.S. government to desist from plans to conduct nuclear tests. During the Cold War, the United States conducted 1030 nuclear weapons tests, more than all other nuclear-armed nations combined (3). In 1996, the United States signed the Comprehensive Nuclear Test Ban Treaty (CTBT), agreeing not to conduct a nuclear weapons test of any yield (4). The United States has not yet ratified the CTBT but did spearhead the 2016 adoption of UN Security Council Resolution 2310, which calls upon all countries to uphold the object and purpose of the CTBT by not conducting nuclear tests (5). Eight of the nine nuclear-armed states, including the five permanent members of the UN Security Council, have observed a moratorium on nuclear testing since 1998 (3, 4). The ninth, North Korea, responding to international pressure, stopped testing warhead detonations (as opposed to missile flights) in 2017 (6). If the United States ratified the CTBT, joining the 168 countries who have already done so (4), there is a good chance that the other holdout countries would ratify the treaty as well (7)

Uphold the nuclear weapons test moratorium

The Trump administration is considering renewing nuclear weapons testing (1), a move that could increase the risk of another nuclear arms race as well as an inadvertent or intentional nuclear war. Following in the long tradition of scientists opposing nuclear weapons due to their harmful effects on both humanity and the planet (2), we ask the U.S. government to desist from plans to conduct nuclear tests. During the Cold War, the United States conducted 1030 nuclear weapons tests, more than all other nuclear-armed nations combined (3). In 1996, the United States signed the Comprehensive Nuclear Test Ban Treaty (CTBT), agreeing not to conduct a nuclear weapons test of any yield (4). The United States has not yet ratified the CTBT but did spearhead the 2016 adoption of UN Security Council Resolution 2310, which calls upon all countries to uphold the object and purpose of the CTBT by not conducting nuclear tests (5). Eight of the nine nuclear-armed states, including the five permanent members of the UN Security Council, have observed a moratorium on nuclear testing since 1998 (3, 4). The ninth, North Korea, responding to international pressure, stopped testing warhead detonations (as opposed to missile flights) in 2017 (6). If the United States ratified the CTBT, joining the 168 countries who have already done so (4), there is a good chance that the other holdout countries would ratify the treaty as well (7)

Large Scale Association Analysis Identifies Three Susceptibility Loci for Coronary Artery Disease

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology

Carburization of steels-An overview

221-228<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">A high carbon upper layer is produced by diffusing carbon and the carburized steel is used in gears, crankshafts where high ware and tare occurs. The thermodynamic, kinetic and transport phenomenon occurring during carburization is studied. Importance of thermochemical phase diagrams to determine the stability region of the oxides and carbides is illustrated. The relationship between the composition of the carburizing atmosphere and the carbon content of the steel is brought out Development of a suitable heat treating environment for obtaining the correct penetration depth is attempted. Mechanism of carburization, kinetic and reaction mechanism of decomposition of gas mixture on the steel surface is described. Models for predicting carburization depth are reviewed. A diffusion model is proposed which is applicable to any diffusion-cum-reaction process. Application and hazards of carburization are explained.</span

Gas-solid reactions: experimental evaluation of the zone model

Zinc sulfide pellets sintered at 1200°C, 1000°C, 800°C and 600°C were partially oxidized in a single pellet reactor. Sulfur profiles of these samples were measured using Auger electron spectroscopy (AES) and electron probe microanalysis (EPMA). These profiles showed the coexistence of three zones: ash layer, reaction zone, and unreacted core. The zone thickness was found to be approximately the same for samples of comparable porosities. The effective diffusivities of sintered zinc sulfide pellets calculated by using the values of zone thickness measured in the present study compare well with the literature values reported from kinetic studies

Gas-solid reactions: a method of direct solution for solid conversion profiles

A new solution technique for non-catalytic gas-solid reactions, which are first order in gas concentration but are represented by any general rate form with respect to the solid, has been proposed. An equation for the variation in conversion with position in the pellet has been derived, the solution of which yields the conversion profiles and the average conversion directly. The method has been illustrated by application to a number of models, such as the particle pellet model with and without structural changes, the volume reaction model, and reactions with significant nucleation effects

A model for gas-solid reactions with structural changes in the presence of inert solids

A mathematical model is developed to account for the effect of inert material present in the solid in noncatalytic gas-solid reactions accompanied by significant structural changes. This model finds application in the desulfurization of flue gases using dolomite, chlorination of ilmenite, etc. where the naturally occurring ores contain inert materials in the solid matrix. The results show that the asymptotic conversion is increased by the presence of inerts and an optimum inert content exists for which the gas uptake and the utilization of the active solid material are maximum

Minimally invasive parathyroidectomy using surgeon-performed ultrasound and sestamibi

Surgeon-performed ultrasound (SPU) and 99mTc-sestamibi (SM) scanning can be used alone or in combination in patients with primary hyperparathyroidism to select cases suitable for minimally invasive parathyroidectomy (MIP). The aim of the study was to evaluate SPU and SM and to determine the reliability they provide the surgeon in planning and carrying out MIP. Methods:  The study was a prospective analysis of 130 patients with primary hyperparathyroidism who had preoperative localization with SPU and SM at a tertiary referral centre between 2003 and 2006. All ultrasound scans were carried out by one surgeon, followed by correlative sestamibi scan and a further `on operating table' ultrasound to reassess the lesion and mark the operative site. Selection criteria for MIP were a positive SPU and SM, although a positive SPU or SM allowed the surgeon to focus on the nominated side. SPU and SM localizations were correlated to the operative findings. Results:  One hundred and thirty patients underwent both SPU and SM. There were 97 women and 33 men, with a mean age of 59 years. SPU alone identified the abnormal parathyroid in 103 cases (sensitivity 82%; positive predictive value 96.3%). SM alone identified the abnormal gland in 102 cases (sensitivity 79%; positive predictive value 99%). In 88 patients, the SPU and SM were concordant, and 94% had successful MIP. SPU and SM were both negative in 13 patients, and all these patients had bilateral neck exploration. Conclusion:  SPU in the hands of an experienced surgeon in association with sestamibi is a reliable tool for the preoperative localization of parathyroid adenomas and facilitates a minimally invasive procedure.Prasannan, Subhita; Davies, Giles; Bochner, Melissa; Kollias, James; Malycha, Pete