Copper- and arsenate-induced oxidative stress in Holcus lanatus L. clones with differential sensitivity

The biochemical responses of Holcus lanatus L. to copper and arsenate exposure were investigated in arsenate‐tolerant and ‐non‐tolerant plants from uncontaminated and arsenic/copper‐contaminated sites. Increases in lipid peroxidation, superoxide dismutase (SOD) activity and phytochelatin (PC) production were correlated with increasing copper and arsenate exposure. In addition, significant differences in biochemical responses were observed between arsenate‐tolerant and ‐non‐tolerant plants. Copper and arsenate exposure led to the production of reactive oxygen species, resulting in significant lipid peroxidation in non‐tolerant plants. However, SOD activity was suppressed upon metal exposure, possibly due to interference with metallo‐enzymes. It was concluded that in non‐tolerant plants, rapid arsenate influx resulted in PC production, glutathione depletion and lipid peroxidation. This process would also occur in tolerant plants, but by decreasing the rate of influx, they were able to maintain their constitutive functions, detoxify the metals though PC production and quench reactive oxygen species by SOD activity.     

Effects of detergents on catalytic activity of human endometase/matrilysin 2, a putative cancer biomarker

Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC₅₀ values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a K_i value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.     

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

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Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology

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Highlights

• •Human spermatozoa possess cells of poor morphology that lack nuclear integrity.
• •These cells can be isolated by density separation.
• •Mass spectrometry reveals their nuclei contain excess protein.
• •TOP2A is a promising marker of this poor nuclear development.

     

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Longitudinal age changes in a fishermen population of West Bengal

The longitudinal anthropological age changes in a sample of coastal fishermen in West Bengal are discussed. The results show that some traits follow the trends observed in ageing of Western populations, for instance nasal length and breadth continue to increase throughout life in both sexes. Stature follows also the trend generally observed: a decrease occurs indeed from 35 years of age in both sexes, the decline is becoming higher with increasing age. The typical ecological conditions of our population influence the rate of change in other traits, such as weight and biacromial diameter. Weight is known to be influenced by the nutritional status and the way of life. It explains that in our study of males an early increase of weight and biacromial diameter is observed first and a decrease afterwards. In females, however, a decrease is observed already from 35 years of age. This kind of analysis was only possible with the help of longitudinal data and in a well defined population: only longitudinal data is free from the effect of secular changes and of selective death.     

Longitudinal patterns of dissolved organic carbon concentration and suspended bacterial density along a blackwater river

Dissolved organic carbon (DOC) is the dominant form of carbon in transport in blackwater rivers, and bacteria are the major biological agents of its utilization. This study describes longitudinal patterns in DOC concentration and relates them to suspended bacterial populations in the channel. Concentrations of total DOC, three molecular weight fractions, and bacterial numbers were determined at 12 sites along the Ogeechee River in 1985–1986 and 1989 during periods of low and high discharge. Suspended bacterial populations were compared with DOC concentrations to determine if differences in bacterial abundance were related to longitudinal patterns of DOC concentration. Three distinct longitudinal patterns were observed: (1) The longitudinal pattern followed by both total and intermediate molecular weight DOC concentrations was a linear function of the geographic distance along the river. (2) During low flow conditions, there was a high degree of correspondence between patterns of bacterial numbers and low MW DOC (< 1000 apparent MW). (3) During periods of high discharge, the proportion of high (> 10,000) and intermediate (1000–10,000) MW fractions increased, and there was no longer a clear relationship between bacterial cells and low MW DOC.     

Design considerations for two-stage enrichment clinical trials

When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a “phase III-like” trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1. By treating these as separate trials, we can gain insight into how the predictive nature of the biomarker specifically impacts the sample size. We also show that failure to adequately estimate the threshold can have disastrous consequences in the second stage. While any bivariate model could be used, we assume a continuous outcome and continuous biomarker, described by a bivariate normal model. The correlation coefficient between the outcome and biomarker is the key to understanding the behavior of the design, both for predictive and prognostic biomarkers. Through a series of simulations we illustrate the impact of model misspecification, consequences of poor threshold estimation, and requisite sample sizes that depend on the predictive nature of the biomarker. Such insight should be helpful in understanding and designing enrichment trials.     

Latent group detection in functional partially linear regression models

In this paper, we propose a functional partially linear regression model with latent group structures to accommodate the heterogeneous relationship between a scalar response and functional covariates. The proposed model is motivated by a salinity tolerance study of barley families, whose main objective is to detect salinity tolerant barley plants. Our model is flexible, allowing for heterogeneous functional coefficients while being efficient by pooling information within a group for estimation. We develop an algorithm in the spirit of the K-means clustering to identify latent groups of the subjects under study. We establish the consistency of the proposed estimator, derive the convergence rate and the asymptotic distribution, and develop inference procedures. We show by simulation studies that the proposed method has higher accuracy for recovering latent groups and for estimating the functional coefficients than existing methods. The analysis of the barley data shows that the proposed method can help identify groups of barley families with different salinity tolerant abilities.