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.     

Allergic Complications of Meningococcal Disease I—Clinical Aspects

Out of 717 patients with meningococcal disease 53 showed one or more of the three allergic complications: 47 (6·6%) developed arthritis, 12 (1·7%) developed cutaneous vasculitis, and 6 developed episcleritis. These complications, which were often multiple, occurred six to nine days after the beginning of the illness and three to six days after the start of successful antibiotic therapy. Those patients with severe systemic disease were prone to the complications.Histological and bacteriological study of the arthritis and vasculitis showed that these lesions were probably not due to persisting infection and suggested that they might be due to immune complex disease.     

Optimisation of the Photonic Efficiency of TiO2 Decorated on MWCNTs for Methylene Blue Photodegradation

MWCNTs/TiO₂ nanocomposite was prepared by oxidising MWCNT in H₂SO₄/HNO₃ then decorating it with TiO₂-p25 nanopowder. The composites were characterised using XRD, TEM, FT-IR PL and UV−vis spectroscopy. The TEM images have shown TiO₂ nanoparticles immobilised onto the sidewalls of the MWCNTs. The UV-vis spectrum confirms that the nanocomposites can significantly absorb more light in the visible regions compared with the commercial TiO₂ (P25). The catalytic activity of these nanocomposites was determined by photooxidation of MB aqueous solution in the presence of visible light. The MWCNTs/TiO₂ (1:3) mass ratio showed maximum degradation efficiency. However, its activity was more favourable in alkaline and a neutral pH than an acidic medium.     

Hybrid Symbiotic Organisms Search Optimization Algorithm for Scheduling of Tasks on Cloud Computing Environment

Cloud computing has attracted significant attention from research community because of rapid migration rate of Information Technology services to its domain. Advances in virtualization technology has made cloud computing very popular as a result of easier deployment of application services. Tasks are submitted to cloud datacenters to be processed on pay as you go fashion. Task scheduling is one the significant research challenges in cloud computing environment. The current formulation of task scheduling problems has been shown to be NP-complete, hence finding the exact solution especially for large problem sizes is intractable. The heterogeneous and dynamic feature of cloud resources makes optimum task scheduling non-trivial. Therefore, efficient task scheduling algorithms are required for optimum resource utilization. Symbiotic Organisms Search (SOS) has been shown to perform competitively with Particle Swarm Optimization (PSO). The aim of this study is to optimize task scheduling in cloud computing environment based on a proposed Simulated Annealing (SA) based SOS (SASOS) in order to improve the convergence rate and quality of solution of SOS. The SOS algorithm has a strong global exploration capability and uses fewer parameters. The systematic reasoning ability of SA is employed to find better solutions on local solution regions, hence, adding exploration ability to SOS. Also, a fitness function is proposed which takes into account the utilization level of virtual machines (VMs) which reduced makespan and degree of imbalance among VMs. CloudSim toolkit was used to evaluate the efficiency of the proposed method using both synthetic and standard workload. Results of simulation showed that hybrid SOS performs better than SOS in terms of convergence speed, response time, degree of imbalance, and makespan.     

The effect of temperature on size and development in three species of benthic copepod

Summary The effect of temperature on the size and development times of three benthic cyclopoid copepods, Acanthocyclops viridis, A. vernalis and Macrocyclops albidus were investigated within the normal environmental temperature range (5°C–20°C). Adult weight decreased as temperature increased. All three species complete their development at 5°C and development times at all temperatures are presented as curvilinear logarithmic temperature functions. The duration of development decreases as temperature rises. The results are compared with those reported else-where for benthic and planktonic species and the ecological implications are discussed.     

Morphine-induced in vivo release of spinal cholecystokinin is mediated by δ-opioid receptors – effect of peripheral axotomy

Morphine and other opioid agonists induce spinal in vivo release of cholecystokinin (CCK), a neuropeptide with anti-opioid properties. However, so far the opioid receptor subtype responsible for this effect has not been determined. In the present in vivo microdialysis study, the morphine-induced release of cholecystokinin-like immunoreactivity (CCK-LI) in the dorsal horn was completely blocked by the delta-opioid antagonist naltrindole (10 microM in the perfusion fluid). Neither the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP; 10 microM in the perfusion fluid), nor the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI); 10 microM in the perfusion fluid) had any significant effect in this respect. In addition, systemic administration of the delta-opioid receptor agonist BW373U86 (1 mg/kg, s.c.) and spinal administration of the delta(2)-opioid receptor agonist, Tyr-D-Ala-Phe-Glu-Val-Val-Gly amide ([D-Ala(2)] deltorphin II) (1 microM in the perfusion fluid) induced a significant increase of the CCK-LI level. The effect of BW373U86 on spinal CCK-LI release was completely blocked by spinal administration of naltrindole. The mu-opioid receptor agonist [D-ala(2)-N-Me-Phe(4)-Gly(5)-ol]-enkephalin (DAMGO) (1 microM in the perfusion fluid or 1 mg/kg, s.c.) failed to alter the CCK-LI level. Peripheral nerve lesions have previously been shown to down-regulate mu- and delta-opioid receptors in the dorsal horn, to increase the gene-expression of CCK and CCK-receptor mRNA in dorsal root ganglion neurons and to alter the potassium-induced spinal CCK-LI release. After complete sciatic nerve transection, administration of the two selective delta-opioid receptor agonists induced a significant release of CCK-LI, which was comparable to controls. In contrast, neither systemic nor spinal administration of morphine and DAMGO altered the spinal CCK-LI release in axotomized animals. The present data indicate that the delta-opioid receptor mediates morphine-induced CCK-LI release in the spinal cord.     

Evaluation of the Potential Therapeutic Properties of Liquidambar orientalis Oil

Liquidambar orientalis Mill., commonly called the Anatolian sweetgum or Sigla tree, is endemic to southwestern Turkey. It has been historically significant in traditional medicine. In our research, we delved into the therapeutic attributes of its oil, emphasizing its antioxidant, antimicrobial, and antitumor properties. The primary chemical constituent of the gum is styrene, accounting for 78.5 %. The gum demonstrated antioxidant capabilities in several assays, including in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP). It displayed bactericidal actions against various gram-positive bacteria, such as Staphylococcus aureus, and gram-negative strains, including Escherichia coli. Additionally, the oil showcased potent antitumor effects against breast (MDA-MB-231), lung (A549), and prostate (PC3) cancer cell lines. These effects were found to be both time- and dose-dependent. L. orientalis Mill. oil showed the best antitumor activity against breast, lung, and prostate cancer cell lines after the 24 h and 48 h treatment. Its oil might induce autophagy in the PC3 prostate cancer cell line, whereas its cytotoxicity against MDA-MB-231 and A549 cancer cell lines might not be correlated with autophagy or apoptosis pathways. In conclusion, the oil from the Sigla tree offers promising therapeutic potential and warrants further exploration.     

Endoplasmic reticulum stress in adipose tissue augments lipolysis

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca²⁺ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24–48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.     

Phosphorus chemistry and bacterial community composition interact in brackish sediments receiving agricultural discharges

Background

External nutrient discharges have caused eutrophication in many estuaries and coastal seas such as the Baltic Sea. The sedimented nutrients can affect bacterial communities which, in turn, are widely believed to contribute to release of nutrients such as phosphorus from the sediment.

Methods

We investigated relationships between bacterial communities and chemical forms of phosphorus as well as elements involved in its cycling in brackish sediments using up-to-date multivariate statistical methods. Bacterial community composition was determined by terminal restriction fragment length polymorphism and cloning of the 16S rRNA gene.

Results and Conclusions

The bacterial community composition differed along gradients of nutrients, especially of different phosphorus forms, from the estuary receiving agricultural phosphorus loading to the open sea. This suggests that the chemical composition of sediment phosphorus, which has been affected by riverine phosphorus loading, influenced on bacterial communities. Chemical and spatial parameters explained 25% and 11% of the variation in bacterial communities. Deltaproteobacteria, presumptively sulphate and sulphur/iron reducing, were strongly associated to chemical parameters, also when spatial autocorrelation was taken into account. Sulphate reducers correlated positively with labile organic phosphorus and total nitrogen in the open sea sediments. Sulphur/iron reducers and sulphate reducers linked to iron reduction correlated positively with aluminium- and iron-bound phosphorus, and total iron in the estuary. The sulphate and sulphur/iron reducing bacteria can thus have an important role both in the mineralization and mobilization of nutrients from sediment.

Significance

Novelty in our study is that relationships between bacterial community composition and different phosphorus forms, instead of total phosphorus, were investigated. Total phosphorus does not necessarily bring out interactions between bacteria and phosphorus chemistry since proportions of easily usable mobile (reactive) phosphorus and immobile phosphorus forms in different sediments can vary. Our study suggested possible feedbacks between different forms of phosphorus and bacterial community composition.     

Control of snakebite envenoming: A mathematical modeling study

A mathematical model is designed to assess the impact of some interventional strategies for curtailing the burden of snakebite envenoming in a community. The model is fitted with real data set. Numerical simulations have shown that public health awareness of the susceptible individuals on snakebite preventive measures could reduce the number of envenoming and prevent deaths and disabilities in the population. The simulations further revealed that if at least fifty percent of snakebite envenoming patients receive early treatment with antivenom a substantial number of deaths will be averted. Furthermore, it is shown using optimal control that combining public health awareness and antivenom treatment averts the highest number of snakebite induced deaths and disability adjusted life years in the study area. To choose the best strategy amidst limited resources in the study area, cost effectiveness analysis in terms of incremental cost effectiveness ratio is performed. It has been established that the control efforts of combining public health awareness of the susceptible individuals and antivenom treatment for victims of snakebite envenoming is the most cost effective strategy. Approximately the sum of US$72,548 is needed to avert 117 deaths or 2,739 disability adjusted life years that are recorded within 21 months in the study area. Thus, the combination of these two control strategies is recommended.