Cloning of the calpain regulatory subunit cDNA from fish reveals a divergent domain-V

Calpains are Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed micro- and m-calpains. Both are heterodimers, consisting of a distinct catalytic subunit and a common regulatory subunit. We describe cloning and sequencing of the calpain small (regulatory) subunit (cpns) cDNA from rainbow trout. This represents the first fish and lower vertebrate full cDNA of cpns. The rainbow trout cpns cDNA was used to retrieve the zebra fish and Japanese flounder homologues. We present evidence that fish cpns, unlike the conventional mammalian predominant isoform, cpnsl, is lacking the glycine-rich region of domain V. Because the glycine-rich region is known to play a role in membrane targeting, this divergent cpns suggests potentially different functional and activation mechanisms of the fish calpain system. A phylogenetic tree for the cpns gene superfamily has been constructed and the evolution of cpns considered.     

Molecular docking analysis of HER-2 inhibitor from the ZINC database as anticancer agents

The human epidermal growth factor (HER2) is a transmembrane receptor that is highly expressed in breast cancer and in different other cancers. Therefore, it is of interest to identify the new HER2 inhibitors from a selected 300 compounds in the ZINC database. The top two hit compounds (ZINC000014780728 (-11.0 kcal/mol) and ZINC000014762512 (-10.8 kcal/mol)) showed a high affinity with HER2 relative to the reference compound (lapatinib (-10.2 kcal/mol)) for further consideration.     

Sizing up human health through remote sensing: uses and misuses

Following the launch of new satellites, remote sensing (RS) has been increasingly implicated in human health research for thirty years, providing a growing availability of images with higher resolution and spectral ranges. However, the scope of applications, beyond theoretical large potentialities, appears limited both by their technical nature and the models developed. An exhaustive review of RS applications in human health highlights the real implication thus far regarding the diversity and range of health issues, remotely sensed data, processes and interpretations. The place of RS is far under its expected potential, revealing fundamental barriers in its implementation for health applications. The selection of images is done by practical considerations as trivial as price and availability, which are often not relevant to addressing health questions requiring suitable resolutions and spatio-temporal range. The relationships of environmental variables from RS, geospatial data from other sources for health investigations are poorly addressed and usually simplified. A discussion covering the potential of RS for human health is developed here to assist health scientists deal with spatial and temporal dynamics of health, by finding the most relevant data and analysis procedures.     

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Salinization of the soil solution decreases the further accumulation of salt in the root zone of the halophyte Atriplex nummularia Lindl. growing above shallow saline groundwater

Water use by plants in landscapes with shallow saline groundwater may lead to the accumulation of salt in the root zone. We examined the accumulation of Na⁺ and Cl^? around the roots of the halophyte Atriplex nummularia Lindl. and the impacts of this increasing salinity for stomatal conductance, water use and growth. Plants were grown in columns filled with a sand–clay mixture and connected at the bottom to reservoirs containing 20, 200 or 400 mM NaCl. At 21 d, Na⁺ and Cl^? concentrations in the soil solution were affected by the salinity of the groundwater, height above the water table and the root fresh mass density at various soil depths (P  < 0.001). However, by day 35, the groundwater salinity and height above the water table remained significant factors, but the root fresh mass density was no longer significant. Regression of data from the 200 and 400 mM NaCl treatments showed that the rate of Na⁺ accumulation in the soil increased until the Na⁺ concentration reached ~250 mM within the root zone; subsequent decreases in accumulation were associated with decreases in stomatal conductance. Salinization of the soil solution therefore had a feedback effect on further salinization within the root zone.     

Regulatory‐associated protein of TOR (RAPTOR) alters the hormonal and metabolic composition of Arabidopsis seeds,controlling seed morphology,viability and germination potential

Target of Rapamycin (TOR) is a positive regulator of growth and development in all eukaryotes, which positively regulates anabolic processes like protein synthesis, while repressing catabolic processes, including autophagy. To better understand TOR function we decided to analyze its role in seed development and germination. We therefore performed a detailed phenotypic analysis using mutants of the REGULATORY‐ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), a conserved TOR interactor, acting as a scaffold protein, which recruits substrates for the TOR kinase. Our results show that raptor1b plants produced seeds that were delayed in germination and less resistant to stresses, leading to decreased viability. These physiological phenotypes were accompanied by morphological changes including decreased seed‐coat pigmentation and reduced production of seed‐coat mucilage. A detailed molecular analysis revealed that many of these morphological changes were associated with significant changes of the metabolic content of raptor1b seeds, including elevated levels of free amino acids, as well as reduced levels of protective secondary metabolites and storage proteins. Most of these observed changes were accompanied by significantly altered phytohormone levels in the raptor1b seeds, with increases in abscisic acid, auxin and jasmonic acid, which are known to inhibit germination. Delayed germination and seedling growth, observed in the raptor1b seeds, could be partially restored by the exogenous supply of gibberellic acid, indicating that TOR is at the center of a regulatory hub controlling seed metabolism, maturation and germination.