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[Display omitted] • Uronate dehydrogenases convert uronic acids in food waste to useful sugar diacids. • Directed evolution was used to improve thermal stability by 18 °C. • X-ray crystal structure showed good side-chain packing and no obvious differences in B-factors compared to wild type. Chromohalobacter salixigens contains a uronate dehydrogenase termed CsUDH that can convert uronic acids to their corresponding C1,C6-dicarboxy aldaric acids, an important enzyme reaction applicable for biotechnological use of sugar acids. To increase the thermal stability of this enzyme for biotechnological processes, directed evolution using gene family shuffling was applied, and the hits selected from 2-tier screening of a shuffled gene family library contained in total 16 mutations, only some of which when examined individually appreciably increased thermal stability. Most mutations, while having minimal or no effect on thermal stability when tested in isolation, were found to exhibit synergy when combined; CsUDH-inc containing all 16 mutations had Δ K t 0.5 +18 °C, such that k cat was unaffected by incubation for 1 h at ∼70 °C. X-ray crystal structure of CsUDH-inc showed tight packing of the mutated residue side-chains, and comparison of rescaled B-values showed no obvious differences between wild type and mutant structures. Activity of CsUDH-inc was severely depressed on glucuronic and galacturonic acids. Combining select combinations of only three mutations resulted in good or comparable activity on these uronic acids, while maintaining some improved thermostability with Δ K t 0.5 ∼+ 10 °C, indicating potential to further thermally optimize CsUDH for hyperthermophilic reaction environments. [ABSTRACT FROM AUTHOR]

Abstract Land-based recirculating aquaculture systems (RAS) have been used to rear salmon from smolt to market-sized adults, but high operating costs have limited their wide spread adoption. One clear advantage of using RAS for salmon aquaculture over open net pens is that fish can be reared under optimal conditions in an attempt to maximize growth and physiological performance and reduce overall production costs. However, few studies have attempted to define the optimal conditions for the long-term rearing of salmon. Thus, the goal of this study is to determine the effects of salinity and photoperiod, two factors that can be easily manipulated in RAS, on the physiological performance of coho salmon (Oncorhynchus kisutch) during long-term rearing. To address this goal, post-smolt coho salmon were reared for 150 days in replicate RAS at 2.5, 5, 10 and 30 ppt under either 12:12 and 24:0 (light:dark) photoperiods. Routine metabolic rate, maximum metabolic rate, aerobic scope and hypoxia tolerance were measured at 60 and 120 days of rearing, while swimming performance was assessed at 60 and 150 days of rearing. There were no effects of salinity or photoperiod on metabolic rate measurements, hypoxia tolerance or swimming performance at any sampling time. There were, however, significant effects of salinity and photoperiod on post-swimming hematology. The results suggest that physiological disturbances continue to manifest due to different environmental conditions, despite acclimation, but do not hinder the animal's ability to cope with physiological stressors. Overall, rearing salinity and photoperiod had very few measurable effects on the physiology and performance of coho salmon except the ionoregulatory disturbances following swimming at salinities of 2.5 and 30 ppt. Highlights In coho salmon reared in RAS at 2.5, 5, 10 or 30 ppt in either 12:12 and 24:0 photoperiods for 150 days we found: • No effect on resting and maximal metabolic rate, or aerobic scope on days 60 or 120 of continuous rearing. • No effect on hypoxia tolerance on days 60 or 120 of continuous rearing. • No effect on repeat swimming performance on days 60 or 150 of continuous rearing despite some ionoregulatory disturbances. • Few physiological disturbances indicating coho salmon seem to acclimate well to these conditions in RAS. [ABSTRACT FROM AUTHOR]

Topic OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI. Clinical Relevance Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD. Methods We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell–inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality. Results We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], –0.46; 95% confidence interval [CI], –0.80 to –0.11; I2 = 71%), GCC thickness (SMD, –0.84; 95% CI, –1.10 to –0.57; I2 = 0%), macular volume (SMD, –0.58; 95% CI, –1.03 to –0.14; I2 = 80%), and macular thickness of all inner and outer sectors (SMD range, –0.52 to –0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, –0.67; 95% CI, –0.95 to –0.38; I2 = 89%) and choroidal thickness (SMD range, –0.88 to –1.03; all P < 0.001) also were thinner in AD patients. Conclusions Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD. [ABSTRACT FROM AUTHOR]

Background and Aims Current evidence of whether distal hyperplastic polyps (HPs) are markers of proximal neoplasia (PN) is mixed. We evaluated the association between distal neoplasia and synchronous PN in asymptomatic subjects. Methods We recruited 5819 Chinese asymptomatic screening participants 50 to 70 years of age who underwent colonoscopy in Hong Kong from 2008 to 2014, of whom 206 subjects with distal advanced neoplasia or cancer were excluded. The association between distal pathology (tubular adenomas [TAs], HPs, no polyps) and proximal pathology (PN, proximal advanced neoplasia [PAN]) was assessed by multivariate regression models, overall and stratified by the Asia Pacific Colorectal Screening scoring system (scores of 4-7, high risk; scores of 0-3, lower risk). Results The prevalence of PN in the no distal polyps group, distal HPs group, and distal TAs group was 14.8%, 19.3%, and 29.4%, respectively. The corresponding prevalence of PAN was 1.8%, 3.2%, and 3.5%. Participants with distal HPs did not have significantly higher odds of PN (adjusted odds ratio [AOR] 1.24; 95% confidence interval [CI], 0.97-1.59; P = .089), and their association with PAN was marginally significant (AOR 1.77; 95% CI, 1.00-3.13; P = .052), except in lower risk subjects for whom the odds of PAN were marginally higher in the distal HPs group than the no distal polyps group (AOR 1.97; 95% CI, 1.01-3.85; P = .048). Overall, the distal polyps group had significantly lower odds of PN than the distal TAs group (AOR 0.55; 95% CI, 0.40-0.76; P < .001). The increased risk of PN and PAN among those with distal HPs was modest. Conclusions A direct association between distal HPs and PN is lacking, and this implies a need for a multivariate assessment of the risk of PAN. Recommending colonoscopy for every patient with distal HPs detected by screening sigmoidoscopy is not supported by this study. [ABSTRACT FROM AUTHOR]

Background & Aims We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. Methods We collected data from 5343 subjects (50−70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT’s sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Results Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%−48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%−34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%−47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%−37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%−48.7%) vs proximal adenoma with 25.3% sensitivity (95% CI, 16.5%−36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%−38.4%) and 92.4% specificity (95% CI, 91.6%−93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%−40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%−92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. Conclusions In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics. [ABSTRACT FROM AUTHOR]

Background Certain subgroups have higher rates of false fecal immunochemical test (FIT) results, yet few studies have addressed this topic. Objective To identify demographic factors associated with false-positive and false-negative FIT results in colorectal cancer screening. Design Retrospective database review of prospectively collected data. Setting A bowel cancer screening center in Hong Kong invited participants for colorectal cancer screening (2008-2012). Patients Study participants who underwent both FIT and colonoscopy in the first year (n = 4482) and underwent colonoscopy after negative FIT results for 3 consecutive years (n = 857). Main Outcome Measurements The diagnostic accuracy and predictive values of FIT according to participant characteristics. Results The sensitivity, specificity, positive predictive values, and negative predictive values for advanced neoplasia were 33.1%, 91.9%, 19.0%, and 96.0%, respectively. Participants 66 to 70 years of age had higher sensitivity, whereas older age, smoking, and use of aspirin/nonsteroidal anti-inflammatory drugs were associated with lower specificity. The rates of false-positive and false-negative results were 8.1% and 66.9%, respectively. Older age (66-70 years; adjusted odds ratio [AOR] 1.95; 95% confidence interval [CI], 1.35-2.81; P < .001), smoking (AOR 1.68; 95% CI, 1.08-2.61; P = .020), and the presence of polypoid adenoma (AOR 1.71; 95% CI, 1.14-2.57; P = .009) were associated with false-positive results. Younger participants (AOR for elderly participants 0.31) and the use of aspirin/nonsteroidal anti-inflammatory drugs (AOR 4.44) in participants with 1 FIT with negative results and the absence of high-grade dysplasia (AOR for presence 0.41) were associated with false-negative results. Limitations Self-referred participants who received one type of qualitative FIT. Conclusion These findings could be used to target screening more toward those with a higher risk of false-negative results and those with a lower risk of false-positive results for earlier colonoscopy. [ABSTRACT FROM AUTHOR]

Abstract: Synchrotron source X-ray micro-computed tomography was used for non-destructive three-dimensional (3-D) imaging of porous alumina structures, in which the porosity was induced by a granular porogen, added in amounts of 10–60vol.%. Microstructural characteristics related to transport properties, including connectivity and tortuosity, were measured from the resulting 3-D data sets. Connectivity of 94.5–99.6% was measured for samples produced with 35–60% porogen (30.8–49.6% porosity). Two methods of calculating tortuosity, path length ratio and gas phase flux were compared, and the effect of sample volume on calculated tortuosity value and computational time was examined. Average sample tortuosity calculated using the two methods generally agreed, although significant directional anisotropy was detected in some cases for the gas phase flux calculation method. Tortuosity values as low as 1.5 were measured for alumina components with 49.6% porosity. [Copyright &y& Elsevier]

Manual handling training may be improved if it relied on the provision of individualized, augmented feedback about key movement features. The purpose of this study was to compare the reduction in sagittal spine motion during manual lifting tasks following two training approaches: didactic (DID) and augmented feedback (AUG). Untrained participants (n = 26) completed lifting tests (box, medication bag, and paramedic backboard) and a randomly-assigned intervention involving 50 practice box lifts. Lifting tests were performed immediately before and after training, and one-week after interventions. Both groups exhibited reductions in spine motions immediately and one-week after the interventions. However, the AUG intervention group elicited significantly greater reductions in 5 of 12 between-group comparisons (3 tasks × 4 spine motion variables). The results of the current study support the use of augmented feedback-based approaches to manual handling training over education-based approaches. [ABSTRACT FROM AUTHOR]

Summary: Esophageal (SE) and tracheoesophageal (TE) speech are the most commonly used alaryngeal voicing types after total laryngectomy—a surgical procedure of removing a pathological larynx. Both SE and TE voices show more aperiodicity than normal laryngeal (NL) voices, and the vocal characteristics of alaryngeal voices are notoriously difficult to extract. The present study investigated the difference in vocal characteristics among NL, SE, and TE voices using perception measures and nonlinear dynamical analysis. Correlation dimension (D 2 ) and sample entropy (SampEn) were obtained from 90 voice samples produced by 10 TE, 10 SE, and 10 NL male Cantonese speakers. Correlation between nonlinear dynamical parameters and perceptual ratings of different voices was also examined. Results show that both D 2 and SampEn values were significantly higher for TE and SE voices than NL voice. The overall perceptual judgment of SE and TE voice quality was negatively correlated with D 2 and SampEn. This finding supports the validity of using nonlinear dynamical parameters in assessing voice quality. Results of the present study also indicate that nonlinear dynamical analysis could be a supplemental tool to traditional acoustic analysis, especially for analyzing the voice quality of alaryngeal speech. [Copyright &y& Elsevier]

To determine the applications of machine learning (ML) techniques used for the primary prevention of work-related musculoskeletal disorders (WMSDs), a scoping review was conducted using seven literature databases. Of the 4,639 initial results, 130 primary research studies were deemed relevant for inclusion. Studies were reviewed and classified as a contribution to one of six steps within the primary WMSD prevention research framework by van der Beek et al. (2017). ML techniques provided the greatest contributions to the development of interventions (48 studies), followed by risk factor identification (33 studies), underlying mechanisms (29 studies), incidence of WMSDs (14 studies), evaluation of interventions (6 studies), and implementation of effective interventions (0 studies). Nearly a quarter (23.8%) of all included studies were published in 2020. These findings provide insight into the breadth of ML techniques used for primary WMSD prevention and can help identify areas for future research and development. [ABSTRACT FROM AUTHOR]

Abstract: A reasonably precise estimate of the thermocline depth (or other well-defined boundaries) in the temperature profile of a lake is of interest to the limnological community. In this article, we propose an empirical model based on the generalized F distribution to describe the temperature profile. Using the model, the thermocline depth can be easily estimated. We also discuss the Gauss–Newton method to fit the model to the profile data. The model fitting procedure is illustrated using data from Lake Whatcom, WA, USA. [Copyright &y& Elsevier]

Abstract: Intestinal trefoil factor (ITF), which is normally absent in gastric mucosa, is over-expressed in gastric cancer. However, the functional significance of ITF in gastric cancer is unknown. We examined the effects of blocking ITF expression on the growth of gastric cancer cells and their responses to chemotherapeutic agents. Anti-sense ITF cDNA was cloned into mammalian expression vector pcDNA3 and was transfected into an ITF-expressing gastric cancer cell line SNU-1. We assessed the doubling time and anchorage dependent growth of the transfected cells using growth curve and soft agar assay respectively. Cell cycle analysis and apoptosis were determined by flow cytometry and cell death ELISA. The response to chemotherapeutic agents after transfecting anti-sense ITF was also examined. Anti-sense ITF transfectant (3A–5) had a significantly longer doubling time as compared to control cells which were transfected with empty vector (32.4 hr vs 26.9 hr, p &#60; 0.05). In the soft agar assay, 3A–5 formed fewer colonies than control (3.5 colonies vs 23.5 colonies, p &#60; 0.05). Although there was no significant difference in the cell cycle distribution between 3A–5 and control, anti-sense ITF resulted in marked increase in adriamycin-induced apoptosis. Our results demonstrated that blocking the expression of ITF inhibits growth of gastric cancer cells and enhances the response to chemotherapy. [Copyright &y& Elsevier]

Abstract: Intestinal trefoil factor (TFF3) is essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. We previously showed that TFF3 was overexpressed in gastric carcinoma. Whether TFF3 possesses malignant potential is not fully elucidated. We sought to investigate the effects of inducting TFF3 expression in a non-malignant rat fibroblast cell line (Rat-2) on the cell proliferation, invasion and the genes regulating cell invasion. Invasiveness and proliferation of transfected Rat-2 cell line were assessed using in vitro invasion chamber assay and colorimetric MTS assay. Differential mRNA expressions of invasion-related genes, namely, metalloproteinases (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), β-catenin and E-cadherin, were determined by quantitative real-time polymerase chain reaction (PCR). We showed that TFF3 did not inhibit the proliferation of Rat-2 cells. We also demonstrated that transfection of TFF3 significantly promoted invasion of Rat-2 cells by 1.4- to 2.2-folds. There was an upregulation of β-catenin (13.1–23.0%) and MMP-9 (43.4–92.2%) mRNA expression levels, and downregulation of E-cadherin (25.6–33.8%) and TIMP-1 (31.5–37.8%) in TFF3-transfected cells compared to controls during 48-h incubation. Our results suggested that TFF3 possesses malignant potential through promotion of cell invasiveness and alteration of invasion-related genes. [Copyright &y& Elsevier]

The effect of vertical confinement on the natural convection flow and heat transfer around a horizontal heated cylinder is investigated. The flow characteristics and the time-resolved heat transfer have been measured respectively above and around the cylinder. It is shown that the primary effect of the vertical confinement is an increase in heat flux on the upper part of the cylinder for given separation distances between the cylinder and the fluid boundary. This increase is shown to be related to the large-scale oscillation of the thermal plume. The relationship between the flow pattern and the heat transfer characteristics at the cylinder surface is studied and the origin of the oscillation discussed. [Copyright &y& Elsevier]

Abstract: Several epidemiologic studies suggest that Fabry disease should be considered in young patients with cryptogenic stroke. We report a case of a young woman presenting with recurrent ischemic strokes who was finally diagnosed with Fabry disease after impaired kidney function had been identified. Fabry disease should be considered in unexplained cases of first or recurrent strokes in young patients disregarding the gender of the patient, especially when chronic kidney disease and/or proteinuria are present. Renal function should be closely monitored in patients with strokes and followed up after the event. In this case, intravenous thrombolysis was performed after the second ischemic event. No other case of thrombolysis for ischemic stroke in Fabry disease has been described in the literature. [Copyright &y& Elsevier]

Abstract Land-based, closed containment salmon aquaculture involves rearing salmon from smolt to adult in recirculating aquaculture systems (RAS). Unlike in open-net pen aquaculture, rearing conditions can be specified in RAS in order to optimize growth and physiological stress tolerance. The environmental conditions that yield optimal stress tolerance in salmon are, however, unknown. To address this knowledge gap, we reared Atlantic (Salmo salar) and coho (Oncorhynchus kisutch) salmon in 7 separate RASs for 400 days post-smoltification under 2 photoperiods (24:0 or 12:12, light:dark) and 4 salinities (2.5, 5, 10 or 30 ppt.) and assessed the effects of these conditions on thermal tolerance. We found that over the first 120 days post-smoltification, rearing coho under a 24:0 photoperiod resulted in a ~2 °C lower critical thermal maxima (CT max) than in coho reared under a 12:12 photoperiod. This photoperiod effect did not persist at 200 and 400 days, which was coincident with an overall decrease in CTmax in coho. Finally, Atlantic salmon had a higher CT max (~28 °C) compared to coho (~26 °C) at 400 days post-smoltification. Overall, these findings are important for the future implications of RAS and for the aquaculture industry to help identify physiologically sensitive time stages. Highlights • In coho salmon, a 24:0 photoperiod significantly reduced CT max relative to a 12:12 photoperiod on days 60 and 120. • CT max decreased over time in coho salmon from approximately 29 °C at 60 days to 26 °C at 400 days post-smoltification. • Salinity had no effect on CTmax in coho or Atlantic salmon. • Atlantic salmon had a higher CT max (28 °C) than coho salmon (26 °C). • This information is important for the aquaculture industry when considering the conditions under which salmon are reared in RAS. [ABSTRACT FROM AUTHOR]

Flexible sigmoidoscopy (FS) and colonoscopy are two commonly used screening tools for colorectal cancer (CRC), and FS mainly detects distal lesions. Colonoscopy resource is limited, yet there is no definite evidence on when flexible sigmoidoscopy is suitable as a screening alternative. This study evaluated the optimal cut-off score from a validated risk stratification system which best predicts proximal advanced neoplasia (PAN) by comparing the sensitivity, specificity and relative risk of PAN according to various cut-off scores. 5819 asymptomatic subjects aged between 50 and 70 years (average age 57.7 years, standard deviation (SD) 4.9) received colonoscopy between 2008 and 2014 in Hong Kong. Their prevalence of PAN was evaluated according to a prediction tool for colorectal neoplasia based on age, gender, smoking status, family history of CRC, body mass index (BMI) and diabetes (ranging from 0 to 6). One binary logistic regression model was performed with PAN as the outcome variable and the risk score as the variable tested for association. In multivariate regression analysis, risk score ⩾3 was associated with significantly higher risk of PAN (3.4–9.1%; AOR = 3.18–8.09, p < 0.001) when compared with those scoring 0. Risk scores 0–2 were associated with either insignificant or lower risks of PAN compared to the overall risk. Applying FS for screening those who scored 0–2 and colonoscopy for those who scored ⩾3 led to a very small proportion of PAN being missed (1.60%), whilst maintaining a high level of specificity (81.9%). Clinicians may use this scoring system to inform subjects and facilitate their choice between colonoscopy and FS. [ABSTRACT FROM AUTHOR]

The enzyme galacturonate oxidoreductase PcGOR from Penicillium camemberti reduces the C-1 carbon of D-glucuronate and C-4 epimer D-galacturonate to their corresponding aldonic acids, important reactions in both pectin catabolism and ascorbate biosynthesis. PcGOR was active on both glucuronic acid and galacturonic acid, with similar substrate specificities (k cat / K m) using the preferred co-substrate NADPH. Substrate acceptance extended to lactone congeners, and D-glucurono-3,6-lactone was converted to L-gulono-1,4-lactone, an immediate precursor of ascorbate. Reaction with glucuronate showed only minor substrate inhibition, and the product L-gulonate and L-gulono-1,4-lactone were both found to be competitive inhibitors with K i in the low mM range. In contrast, reaction with C-4 epimer galacturonate displayed marked substrate inhibition. Moreover, the product L-galactonate and L-galactono-1,4-lactone were observed to mitigate substrate inhibition by galacturonate, with the lactone having a greater effect than the acid. [ABSTRACT FROM AUTHOR]

Two GH43 β-xylosidases, RS223-BX from a rice straw metagenomic library, and BoXA from Bacteroides ovatus , that share similar amino acid sequences (81% identical) and 19 of 20 active-site residues, were compared by using site-directed mutagenesis of Asp and His residues implicated in metal binding. Thus, RS223-BX is strongly activated by divalent-metal cations and the previously published X-ray structure of this enzyme shows that a Ca 2+ cation is chelated by an active-site Asp carboxyl group and an active-site His. Mutation to Ala causes 90% loss of activity for the Asp mutant and 98% loss of activity for the His mutant, indicating their importance to catalysis. For the other enzyme (BoXA), mutation to Ala causes 20% loss of activity for the His mutant and 40% gain of activity for the Asp mutant, indicating the lack of importance for activity of the native residues and the lack of metal-dependency, given that the Asp residue occupies the active site to secure the metal cation in known metal ion dependent GH43 xylosidases. The high activity of the BoXA mutants compared to that of the analogous RS223-BX mutants further undermines the possibility that BoXA maintains a tightly bound metal cofactor resistant to EDTA extraction. The results strengthen our conclusion that the very similar proteins differ in one being metal ion dependent and one not. [ABSTRACT FROM AUTHOR]

Enzyme catalysts will be vital in the development of synthetic biology approaches for converting pectinic monosaccharides from citrus and beet processing waste streams to value-added materials. We describe here the biophysical and mechanistic characterization of uronate dehydrogenases from a wide variety of bacterial sources that convert galacturonic acid, the predominate building block of pectin from these plant sources, and glucuronic acid to their corresponding dicarboxylic acids galactarate and glucarate, the latter being a DOE top value biochemical from biomass. The enzymes from Pseudomonas syringae and Polaromonas naphthalenivorans were found to have the highest reported k cat (glucuronic acid) values, on the order of 220–270 s −1 . The thermal stability of this enzyme type is described for the first time here, where it was found that the K t (0.5) value range was >20 °C, and the enzyme from Chromohalobacter was moderately thermostable with K t (0.5) = 62.2 °C. The binding mechanism for these bi-substrate enzymes was also investigated in initial rate experiments, where a predominately steady-state ordered binding pattern was indicated. [ABSTRACT FROM AUTHOR]

Background: The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. Purpose: To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Methods: Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. Results: The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, p<0.001); overweight (BMI=23−24.9, AOR=1.52, 95% CI=1.12, 2.07, p=0.007); obesity (BMI≥25, AOR=1.56, 95% CI=1.15, 2.10, p=0.004); hypertension (AOR=1.58, 95% CI=1.21, 2.06, p=0.001); and alcohol consumption (AOR=1.47, 95% CI=1.05, 2.06, p=0.025) were associated with ACN. The c-statistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Conclusions: Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. [Copyright &y& Elsevier]

Abstract: Renal toxicity can commonly occur after exposure to xenobiotics, pharmaceutical agents or environmental pollutants. Changes in the gene expression in kidney parenchymal cells that precede and/or accompany renal injury may be hallmark critical events in the onset of pathologic changes of renal functions. Over the last several years, transcriptomic analysis has evolved to enable simultaneous analysis of the expression profiles of tens of thousands of genes in response to various endogenous and exogenous stimuli. In this study, we investigated gene expression changes in the kidney after acute exposure to a nephrotoxin, d-serine, which targets the proximal tubule of the kidney. Male F-344 rats injected intraperitoneally with a single dose of d-serine (5, 20, 50, 200 or 500mg/kg), and gene expression profiles in the kidney were determined using the Affymetrix RAE230A gene arrays at 96h post-dosing. d-Serine treatment resulted in the up- and down-regulation of 1158 and 749 genes, respectively, over the entire dose range based on the intersection of the results of t-test, p <0.01 over two consecutive doses, and ANOVA with Bonferonni correction for multiple testing. Interestingly, both the up-and down-regulated genes show a unified dose response pattern as revealed in the self-organized map clustering analysis using the expression profiles of the 1907 differentially expressed genes as input data. There appears to be minimal changes in the expression level of these genes in the dose range of 5–50mg/kg, while the most prominent changes were observed at the highest doses tested, i.e. 200 and 500mg/kg. Pathway analysis of the differentially expressed genes showed perturbation of a large number of biological processes/pathways after d-serine exposure. Among the up-regulated pathways are actin cytoskeleton biogenesis and organization, apoptosis, cell cycle regulation, chromatin assembly, excision repair of damaged DNA, DNA replication and packaging, protein biosynthesis, metabolism and transport, inflammatory response, proteasome-mediated degradation of oxidatively damaged cytosolic proteins, Ras protein signal transduction, TGF-beta signaling pathway and mRNA transcription, processing, splicing and transport. On the other hand, major metabolic pathways, which include carbohydrate metabolism, TCA cycle, oxidative phosphorylation, ATP synthesis coupled electron transport, amino acid metabolism and transport, lipid metabolism, nucleotide metabolism, and vitamin metabolism, and oxidative stress response including induction of antioxidant genes and glutathione metabolism are down-regulated. As tubular epithelia have strong energy demand for normal functions, down-regulation of energy metabolism after d-serine treatment may be related to the mechanism of its nephrotoxicity. In addition, hydrogen peroxide, a reactive oxygen species, is produced as a byproduct of the metabolism of d-serine by d-amino acid oxidase in the peroxisomes of the tubular epithelia. Down-regulation of pathways for antioxidant genes induction and glutathione metabolism will likely exacerbate the cytotoxicity of this reactive oxygen species. The observation that the genes involved in apoptosis, DNA repair, proteasome pathway for the degradation of oxidatively damaged cytosolic proteins were up-regulated lends some supports to this premise. Up-regulation of pathways of cell proliferation cycle, DNA replication and gene expression process, including mRNA transcription, processing, splicing, transport, translation initiation, and protein transport along with protein complex assembly, suggests ongoing tissue repair and regeneration. Consistent with the fibrogenic function of the TGF-beta signaling pathway in various experimental renal diseases, genes encoding major extracellular matrix components such as collagens, laminins, fibronectin 1 and tenascins are also strongly up-regulated. Taken together, the results of this study provide important insights into the molecular mechanism of d-serine nephrotoxicity, as well as the activation of specific cellular pathways in response to this toxic insult. [Copyright &y& Elsevier]

Complementary metal-oxide-semiconductor (CMOS) transistor scaling will continue for at least another decade. However, innovation in transistor structures and integration of novel materials are needed to sustain this performance trend. Here we discuss the challenges and opportunities of transistor scaling for the next five to ten years. [Copyright &y& Elsevier]

Abstract: We characterized the effects of selective Cox-2 inhibition on the angiogenesis gastric cancer cell line SGC7901 by stable transfection of antisense Cox-2 cDNA (Cox-2-AS) or pharmacological inhibition by selective cox-2 inhibitor (NS398). The conditioned media obtained from SGC7901 treated with Cox-2-AS or NS398 suppressed the proliferation, migration and tube formation of human umbilical vein endothelial cells. Moreover, both treatments inhibited in vivo angiogenesis. These inhibitions could be partially reversed by the addition of PGE2. Our findings support that selective inhibition of Cox-2 alone plays an instrumental role on gastric cancer associated angiogenesis. [Copyright &y& Elsevier]