Structure of the Non-Catalytic Domain of the Protein Disulfide Isomerase-Related Protein (PDIR) Reveals Function in Protein Binding

Protein disulfide isomerases comprise a large family of enzymes responsible for catalyzing the proper oxidation and folding of newly synthesized proteins in the endoplasmic reticulum (ER). Protein disulfide isomerase-related (PDIR) protein (also known as PDIA5) is a specialized member that participates in the folding of α₁-antitrypsin and N-linked glycoproteins. Here, the crystal structure of the non-catalytic domain of PDIR was determined to 1.5 Å resolution. The structure adopts a thioredoxin-like fold stabilized by a structural disulfide bridge with a positively charged binding surface for interactions with the ER chaperones, calreticulin and ERp72. Crystal contacts between molecules potentially mimic the interactions of PDIR with misfolded substrate proteins. The results suggest that the non-catalytic domain of PDIR plays a key role in the recognition of protein partners and substrates.     

Influence of HOCl…O3 and HOCl…HOCl interactions on the stability of O3(HOCl)2 complexes: a theoretical study

We have analysed the role of HOCl…O₃ and HOCl…HOCl interactions on the stability of four estimated O₃(HOCl)₂ complexes by means of ab initio molecular orbital calculations. It is predicted that the O₃(HOCl) + HOCl reaction is more energetically favourable than (HOCl)₂ + O₃ one. In all complexes, HOCl…HOCl interaction is stronger than HOCl…O₃ one. The results show that the HOCl…O₃ interaction strengthens the HOCl…HOCl one. On the other hand, O…H interaction in HOCl…O₃ moiety is strengthened when it interacts with HOCl. Quantum theory of atoms in molecules predicts that the weak interactions in O₃(HOCl)₂ complexes have electrostatic characteristic. In all complexes, the charge transfer from O₃ to (HOCl)₂ is expected from natural bond orbital analysis.     

Role of Bacillus licheniformis in Phytoremediation of Nickel Contaminated Soil Cultivated with Rice

Heavy metal contamination in soil is an important environmental problem and it has negative effect on agriculture. Bacteria play a major role in phytoremediation of heavy metals contaminated soil. In this study, the effect of Bacillus licheniformis NCCP-59, a halophilic bacterium isolated from salt mines near Karak, Pakistan, were determined on a three week old greenhouse grown seedling and germinating seeds of two rice varieties (Basmati-385 (B-385) and KSK-282) in soil contaminated with different concentrations (0, 100, 250, 500, and 1000 ppm) of Nickel. Nickel significantly reduced the germination rate and germination percentage mainly at 500 and 1000 ppm. Significant decrease in ion contents (Na, K, and Ca) was observed while Ni ion concentration in the plant tissues increases as the concentration of Ni applied increases. The photosynthetic pigments (chlorophyll a (chl a), chlorophyll b (chl b), and carotenoids) were also decreased by the application of different concentrations of Ni. Total protein and organic nitrogen were found to be reduced at higher concentrations of Nickel. Inoculation of Bacillus Licheniformis NCCP-59 improved seed germination and biochemical attribute of the plant under Ni stress. It is clear from the results that the Bacillus Licheniformis NCCP-59 strain has the ability to protect the plants from the toxic effects of nickel and can be used for the phytoremediation of Ni contaminated soil.     

Biocalcification by halophilic bacteria for remediation of concrete structures in marine environment

Microbial carbonate precipitation has emerged as a promising technology for remediation and restoration of concrete structures. Deterioration of reinforced concrete structures in marine environments is a major concern due to chloride-induced corrosion. In the current study, halophilic bacteria Exiguobacterium mexicanum was isolated from sea water and tested for biomineralization potential under different salt stress conditions. The growth, urease and carbonic anhydrase production significantly increased under salt stress conditions. Maximum calcium carbonate precipitation was recorded at 5 % NaCl concentration. Application of E. mexicanum on concrete specimens significantly increased the compressive strength (23.5 %) and reduced water absorption about five times under 5 % salt stress conditions compared to control specimens. SEM and XRD analysis of bacterial-treated concrete specimens confirmed the precipitation of calcite. The present study results support the potential of this technology for improving the strength and durability properties of building structures in marine environments.     

Activation of ER stress signalling increases mortality after a major trauma

The endoplasmic reticulum (ER) adapts to stress by activating a signalling cascade known as the ER stress response. While ER stress signalling is a central component of the cellular defence against environmental insult, persistent activation is thought to contribute to the progression of various metabolic complications via loss of protein function and cell death. Despite its importance however, whether and how ER stress impacts morbidity and mortality in conditions of hypermetabolism remain unclear. In this study, we discovered that chronic ER stress response plays a role in mediating adverse outcomes that occur after major trauma. Using a murine model of thermal injury, we show that induction of ER stress with Tunicamycin not only increased mortality but also resulted in hepatic damage and hepatic steatosis. Importantly, post‐burn treatment with chaperone ER stress inhibitors attenuated hepatic ER stress and improved organ function following injury. Our study identifies ER stress as a potential hub of the signalling network affecting multiple aspects of metabolism after major trauma and as a novel potential molecular target to improve the clinical outcomes of severely burned patients.     

Heart Failure Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Background

Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.

Methods and Findings

Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.

Conclusions

The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors'' Summary     

Radiosynthesis,radiochemical, and biological characterization of 177Lu-labeled diethylenetriamine penta-acetic acid

Diethylenetriamine penta-acetic acid (DTPA), when complexed with a gamma (γ)-emitter radioisotope like ^99mTc, is used for renal function diagnosis and many other diagnostic applications. The main aim of this study was to develop a novel and versatile single-step methodology for the synthesis of a new ¹⁷⁷Lu-labeled radiopharmaceutical with high radiochemical yield, which can be used for diagnostic purposes and therapeutic purposes also. The single and well-defined ¹⁷⁷Lu-DTPA complex was radiochemically characterized by paper chromatography, thin-layer chromatography, high-performance liquid chromatography, and electrophoresis techniques. Dependence of the labeling yield of ¹⁷⁷Lu-DTPA complex on different factors was studied in detail. Biological evaluation was also performed in a normal rabbit by developing images under a γ camera at various time intervals. More than 99% labeling yield was obtained by reacting DTPA with ¹⁷⁷Lu at specific conditions (pH 7.0, 15 minutes reaction time at 100 °C). ¹⁷⁷Lu-DTPA complex showed high stability both at room temperature and in vitro. Biodistribution studies in normal mice indicated the fractional renal uptake of intravenously administered ¹⁷⁷Lu-DTPA complex, which reached in the kidneys within 2-3 minutes. Scintigraphy showed rapid clearance from the body. Based on these results, we propose that ¹⁷⁷Lu-DTPA complex might be used as an ideal candidate for functional evaluation of kidneys and the urinary tract, especially when needed to be transported to long-range consumer sites, because of its suitable half-life.