Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase.

The ubiquitin-specific protease USP7/HAUSP regulates p53 and MDM2 levels, and cellular localization of FOXO4 and PTEN, and hence is critically important for their role in cellular processes. Here we show how the 64 kDa C-terminal region of USP7 can positively regulate deubiquitinating activity. We present the crystal structure of this USP7/HAUSP ubiquitin-like domain (HUBL) comprised of five ubiquitin-like (Ubl) domains organized in 2-1-2 Ubl units. The last di-Ubl unit, HUBL-45, is sufficient to activate USP7, through binding to a “switching” loop in the catalytic domain, which promotes ubiquitin binding and increases activity 100-fold. This activation can be enhanced allosterically by the metabolic enzyme GMPS. It binds to the first three Ubl domains (HUBL-123) and hyperactivates USP7 by stabilization of the HUBL-45-dependent active stat

Cyclic activity in the digestive diverticula of Sunetta scripta in accordance with tides

Feeding and digestion in bivalves are considered to be continuous and simultaneous. The tide influenced physiological changes in the digestive diverticula of Sunetta scripts on the basis of histological observation was studied. The shape of the digestive diverticula changes in accordance with the tidal level. The maximum pH value in the mantle cavity was recorded at high tide (7.46) when the animal was covered by the almost static tidal water, the constancy in the pH of the mantle cavity was due to the renewal of the water in the mantle cavity. At low tide the pH gradually comes down to 6.87 due to the exposure of the animal and the subsequent non-renewal of water in the mantle cavit

THE BEST PREDICTORS OF INDUSTRIAL SICKNESS -ACCRUAL RATIOS OR CASH FLOW RATIOS?

Abstract Indian industry has been witnessing tremendous progress in the recent decades thanks to the industrial reform INTRODUCTION A company's health can easily be evaluated from all possible dimensions using financial ratios. Several researchers have found accrual ratios well predicting corporate sickness. Patrick (1932) was pioneer in forecasting corporate failure, showing that net worth to debt and net profits to net worth were the predictors of sickness among the ratios he used

Biochar synthesis from mineral and ash-rich waste biomass, part 2: characterization of biochar and co-pyrolysis mechanism for carbon sequestration

The increase in mineral and ash-rich waste biomass (MWB) generation in emerging economies poses critical environmental problems and bottlenecks the solid waste and wastewater treatment systems. Transforming these MWB such as sewage sludge from wastewater treatment (SSW) to biochar can be a sustainable method for their disposal and resource recovery. However, such biochar has limited applicability due to the relatively low organic content and possibly contaminated nature of SSW. This may be offset through combined pyrolysis with other MWB, which can also support municipal solid waste management. Studies on this MWB co-pyrolysis are lacking and have not yet seen successful long-term implementation. This work is the second part of authors’ research encompassing an analytical and lab-scale investigation of biochar production from MWB through pyrolysis for the case of Chennai city, India. Here, the physicochemical properties of biochar derived from lab-scale co-pyrolysis of SSW with other MWB such as anaerobic digestate from waste to energy plants of food, kitchen or market waste fermentation, and banana peduncles (BP) collected from vegetable markets and their thermolysis mechanism are comprehensively investigated for purpose of carbon sequestration. Also, a novel preliminary investigation of the effect of sample weight (scaling effect) on the analytical pyrolysis of biomass (BP as model substrate) is undertaken to elucidate its impact on the heat of pyrolysis and carbon distribution in resultant biochar. The maximum carbon sequestration potential of the derived biochar types is 0.22 kg CO2 kg−1 biomass. The co-pyrolysis of MWB is exothermic and governed by the synergetic effects of the components in blends with emission profiles following the order CO2 > CH4 > CO > NH3. Co-pyrolysis reduced the heavy metal enrichment in SSW biochar. The derived biochars can be an immediate source of N, P and S in nutrient-deficient acidic soils. The biochar has only up to 4-ring polyaromatic compounds and a residence time longer than 1 h at 500 °C is necessary to improve carbonization. The heat released during analytical pyrolysis of the model biomass and distribution of carbon in the resultant biochar are significantly influenced by scaling effects, drawing attention to the need for a more detailed scaling investigation of biomass pyrolysis

Oxidation-resistant interfacial coatings for continuous fiber ceramic composites

Developing an oxidation-resistant interfacial coating for continuous fiber ceramic composites (CFCCs) continues to be a major challenge. CFCCs` mechanical behavior are influenced by the interfacial bonding characteristics between the fiber and the matrix. Finite element modeling studies suggest that a low-modulus interfacial coating material will be effective in reducing the residual thermal stresses that are generated upon cooling from processing temperatures. Nicalon/SiC composites with carbon, alumina and mullite interfacial coatings were fabricated with the SiC matrix deposited using a forced-flow chemical vapor infiltration process. Composites with mullite interfacial coatings exhibited considerable fiber pull-out even after oxidation and have potential as a composite system

The Hydrophobic Core of Twin-Arginine Signal Sequences Orchestrates Specific Binding to Tat-Pathway Related Chaperones

Redox enzyme maturation proteins (REMPs) bind pre-proteins destined for translocation across the bacterial cytoplasmic membrane via the twin-arginine translocation system and enable the enzymatic incorporation of complex cofactors. Most REMPs recognize one specific pre-protein. The recognition site usually resides in the N-terminal signal sequence. REMP binding protects signal peptides against degradation by proteases. REMPs are also believed to prevent binding of immature pre-proteins to the translocon. The main aim of this work was to better understand the interaction between REMPs and substrate signal sequences. Two REMPs were investigated: DmsD (specific for dimethylsulfoxide reductase, DmsA) and TorD (specific for trimethylamine N-oxide reductase, TorA). Green fluorescent protein (GFP) was genetically fused behind the signal sequences of TorA and DmsA. This ensures native behavior of the respective signal sequence and excludes any effects mediated by the mature domain of the pre-protein. Surface plasmon resonance analysis revealed that these chimeric pre-proteins specifically bind to the cognate REMP. Furthermore, the region of the signal sequence that is responsible for specific binding to the corresponding REMP was identified by creating region-swapped chimeric signal sequences, containing parts of both the TorA and DmsA signal sequences. Surprisingly, specificity is not encoded in the highly variable positively charged N-terminal region of the signal sequence, but in the more similar hydrophobic C-terminal parts. Interestingly, binding of DmsD to its model substrate reduced membrane binding of the pre-protein. This property could link REMP-signal peptide binding to its reported proofreading function

To hit or not to hit, that is the question -genome-wide structure-based druggability predictions for <i>pseudomonas aeruginosa </i>proteins

Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa

The Plasmodium Export Element Revisited

We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide