Miracle-dz/UniFAR-FTUs huggingface dataset:
ICP34.5 Protein of Herpes Simplex Virus Facilitates the Initiation of Protein Translation by Bridging Eukaryotic Initiation Factor 2α (eIF2α) and Protein Phosphatase 1*

The ICP34.5 protein of herpes simplex virus type 1 is a neurovirulence factor that plays critical roles in viral replication and anti-host responses. One of its functions is to recruit protein phosphatase 1 (PP1) that leads to the dephosphorylation of the α subunit of translation initiation factor eIF2 (eIF2α), which is inactivated by infection-induced phosphorylation. As PP1 is a protein phosphatase with a wide range of substrates, the question remains to be answered how ICP34.5 directs PP1 to specifically dephosphorylate eIF2α. Here we report that ICP34.5 not only binds PP1 but also associates with eIF2α by in vitro and in vivo assays. The binding site of eIF2α is identified at amino acids 233–248 of ICP34.5, which falls in the highly homologous region with human gene growth arrest and DNA damage 34. The interaction between ICP34.5 and eIF2α is independent of the phosphorylation status of eIF2α at serine 51. Deletion mutation of this region results in the failure of dephosphorylation of eIF2α by PP1 and, consequently, interrupts viral protein synthesis and replication. Our data illustrated that the binding between viral protein ICP34.5 and the host eIF2α is crucial for the specific dephosphorylation of eIF2α by PP1. We propose that herpes simplex virus protein ICP34.5 bridges PP1 and eIF2α via their binding motifs and thereby facilitates the protein synthesis and viral replication.
Isolation and characterization of alkaline protease-deficient mutants of Pseudomonas aeruginosa in vitro and in a mouse eye model

Mutants of Pseudomonas aeruginosa are described which are markedly deficient in alkaline protease production. Characterization of these mutants in vitro suggests that the mutations in two of these strains are specific for alkaline protease production. Examination of these mutants in a mouse eye model demonstrates that alkaline protease is required for the establishment of corneal infections with P. aeruginosa PA103. Mutants deficient in alkaline protease production could not colonize traumatized cornea and did not produce the corneal damage characteristic of infection by the parental strain. Addition of subdamaging amounts of alkaline protease to eyes infected with the protease-deficient mutants resulted in infections which were indistinguishable from infections caused by the parental strain.
Transfusion support by a UK Role 1 medical team: a 2-year experience from Afghanistan

Introduction This paper describes the clinical governance, training, equipment and infrastructure developed to enable a UK Role 1 medical team to deliver forward transfusion in Southern Afghanistan. The aim was to explore the utility and feasibility of forward blood transfusion by a Role 1 medical team in an austere military environment. Methods An audit of prospectively collected transfusion regulatory and cold chain data using standard-issue equipment and governance systems. TempIT tags were read before and after each mission to record blood storage temperature. Two years’ data were analysed to review the use of blood products, cold chain compliance and equipment issues. Results Over 24 months, blood products were carried on over 1000 mission hours. Two clinical cases required transfusion and were successfully resuscitated. The team was able to correctly transport, store and deploy red cells and plasma on missions using standard Ministry of Defence (MOD) issue equipment. There were seven cold chain failures, all of which were addressed locally. Current cold chain and diagnostic equipment would require further optimisation for use at Role 1. Conclusions An isolated Role 1 medical team can safely deliver blood transfusion on vehicle, helicopter or foot patrols. The transport and storage of blood created a large logistical burden for a relatively small clinical output. However, with further developments, this capability may have utility in contingency operations especially for isolated teams.
Wi-Fi On Steroids : 802 . 11 ac and 802

The advent of bandwidth hungry wireless applications such as large file transfers, high definition video streaming, wireless display, and cellular data offload highlight the impending need for larger bandwidth and super speed Wi-Fi links exceeding 1 Gbps. This article introduces two emerging standards likely to shake the wireless world, namely IEEE 802.11ac and IEEE 802.11ad, and identifies the challenges in the path of multi-gigabit Wi-Fi. We study the suitability of these standards for the new usage models enlisted in this article.
Coevolution of cooperation, causal cognition and mindreading

The evolution of cooperation between unrelated individuals has long been a puzzle in evolutionary biology. Formal models show that reciprocal altruism is approximately as stable as kin-based altruism when cooperators can assort. Why, then, is reciprocal altruism so rare? We suggest that the key lies in the difficulty of assortment based on underlying intentions: if individuals are able to reliably detect others’ cooperative intent then cooperation is stable, but detecting intentions is notoriously difficult, especially when there are incentives to deceive. For this reason, we suggest, there is likely to be a coevolutionary relationship between human cooperativeness and our skills of social causal cognition: it is not a coincidence that we are both extraordinarily social, cooperating with non-kin to a degree not seen in other species, and extraordinarily good at inferring others’ beliefs, intentions, and motivations, a skill sometimes known as mindreading. We discuss results of a recent study that provides evidence for this coevolutionary view of cooperation and social cognition.
Coherent optical beomforming techniques

Future phased array antennas will have stringent requirements in terms of performance, mass and power, which can be efficiently met by optoelectronic techniques. By employing coherent optical processing in guided-wave optical components, and with extensive use of optoelectronic integrated circuits, substantial reductions in mass and power are feasible in comparison with conventional beamformers. In a major study for European Space Agency, reductions of 30% and power reductions of 60% were seen to be feasible in a complex beamformer for a space-borne communications antenna, relative to a MMIC-based system with the same performance requirements. In order to verify the system concept, we designed and constructed a complete proof of concept model (PCM) offering both transmit and receive mode operation in the 12 GHz band. Detailed performance evaluation has been carried out, resulting in the first practical demonstration of the application of coherent optical techniques in an antenna beamformer. In this paper we discuss the optoelectronic beamforming concept, the application of this concept to a specific antenna and the design and construction of the proof of concept model.
Monosodium glutamate induces apoptosis in naive and memory human B cells.

The aim of this study was to establish the existence of mGluR7 in normal B lymphocytes and analyse the effect of monosodium glutamate (MSG) on B cell apoptosis in vitro. B cells were purified by magnetic cell sorting using anti-CD19-coupled magnetic beads. Cells (10(6)/ml) were cultured with increasing MSG concentrations (1-100 mM). Detection of apoptosis by flow cytometry was performed using the Annexin V-FITC/Propidium iodide (PI) apoptosis detection kit. Naïve and memory B cell population were identified by CD27 staining. Expression of GluRs was determined using PCR. Exposure to increasing MSG concentrations displayed dose dependent effect on B cell viability altogether, ranging from 35% with 100 mM up to 80% with 1 mM MSG. Moreover, the number of late apoptotic cells as well as necrotic cells was dose dependant. Both CD27- as well as CD27+ B cells were affected by MSG. Basal expression of GluRs7 was detected in unstimulated B cells. Glutamate induced apoptosis can be seen in memory as well as naive B cell population and is probably mediated through mGluR7, whose expression in B cells we also confirmed. Our study suggests a new possible mechanism of crosstalk between the nervous and the immune system through glutamate as a potential key mediator (Fig. 4, Ref. 27). Full Text (Free, PDF) www.bmj. sk.
The role of ionic release from NovaMin (calcium sodium phosphosilicate) in tubule occlusion: an exploratory in vitro study using radio-labeled isotopes.

OBJECTIVE The primary objective of this work was to develop a method of quantifying the levels and source of calcium and phosphate deposited on dental hard tissue from a novel calcium phosphosilicate (NovaMin) material using neutron activation analysis (NAA). A second objective was to explore the utility of radiotracing to determine dentin porosity following exposure to calcium phosphosilicate. METHODS Neutron activation was used to create isotopes of Ca and P in the calcium phosphosilicate particles. Gamma radiation emitted from these isotopes was used to identify and measure their uptake (concentration) onto dental hard tissue. Three experiments were conducted to explore calcium and phosphate uptake to dental hard tissue: 1) a dose response to quantify the relative levels of calcium and phosphate deposited on dental hard tissue as a function of calcium phosphosilicate dose; 2) the effect of calcium phosphosilicate particle size on the relative levels of calcium and phosphate uptake; and 3) the permeability of calcium phosphosilicate-treated dentin by employing the radiotracer technetium. For all experiments, extracted bovine incisors were employed as the test substrate. RESULTS The results indicate there is a strong dose relationship between the wt% and particle size of calcium phosphosilicate in the dentifrice formulation and new Ca and P deposition. At above 5.0 wt% calcium phosphosilicate, there appears to be an exponential increase in the number of counts from the tooth surface. Finer particle size calcium phosphosilicate appears to deposit much higher levels of Ca and P than the larger range of particle sizes. The results from the technetium study show that when treated with the dentifrice slurry containing calcium phosphosilicate, dentin shows only a slight amount of technetium infiltration, indicating a lowering of dentin permeability. CONCLUSION This exploratory study has demonstrated that NAA and the use of radio isotopes have utility in monitoring the uptake of Ca and P into both dentin and enamel tooth structure. The data generated from these studies have shown that there is a dose dependence and particle size effect for calcium phosphosilicate on the deposition of calcium and phosphate to dental hard tissue.
Concentration‐dependent effects on the rapid and efficient activation of the MAP kinase signaling cascade

Modern proteomic techniques are making it possible to identify and quantitate increasingly complex mixtures of cellular proteins. Translating the relative expression measurements collected in these experiments into an understanding of the associated physiological phenomena continues to be a challenge for the field of systems biology. We demonstrate how methods of mathematical and computational systems biology permit us to proffer explanations for the observed concentration ranges of signaling components found in the highly conserved mitogen‐activated protein kinase (MAPK) cascade. The analysis demonstrates that alterations in the naturally occurring MAPK and MAPK kinase (MAPKK) concentrations would negatively affect the efficiency of short‐term responses of the cascade. Thus, while there seems to be no a priori rationale for particular features of the involved kinases, the observed ranges of their characteristic parameters appear to be far from coincidental. This result is deduced from the first principles of mass action kinetics and holds for wide variations in MAPKK kinase (MAPKKK) concentrations, differential preference for unphosphorylated and monophosphorylated forms of kinase substrates, and for cases where the monophosphorylated MAPKK exhibits kinase activity. The results demonstrate how theoretical systems biology complements molecular biology by providing specific rationale for observed natural designs in a fashion hardly achievable with experimentation alone.
The Epidemiology of Early Schizophrenia

For the investigation of the early course of schizophrenia starting from onset, the standardised Interview for the Retrospective Assessment of the Onset of Schizophrenia was developed and validated. In a representative sample of 267 first-admitted German schizophrenics of a broad diagnosis from a population of 1.5 million, the age at which different diagnostic and onset definitions were satisfied, the symptoms at the time of the interview, and the accumulation of positive and negative symptoms until first admission were assessed. Comparison between the two sexes and three age groups yielded hardly any differences in the accumulation of symptoms and their course until first admission, except for a slightly shorter period of negative symptoms in young males and a slightly longer one in older women – which contradicts prevailing opinion. At the time of the interview, no significant sex differences were found with respect to the core symptoms of schizophrenia (negative and first-rank symptoms), but clear and substantial differences emerged in disease behaviour. The significantly higher age at first onset in women is explained, on the basis of animal experiments and a clinical study, by the neuromodulatory effect of oestrogen on D2 receptors and by a higher vulnerability threshold in women.
Frailty Syndrome is Associated with Altered Circulating Redox Balance and Increased Markers of Oxidative Stress

Frailty Syndrome (FS) is a condition described in aging and characterized by physical vulnerability to stress and lack of physiological reserve. In this study we aim to define whether circulating oxidative stress correlates to frailty in terms of glutathione balance and oxidative protein damage. In 62 elderly outpatients, classified as frail patients according to Fried's criteria, evaluation of reduced Glutathione (GSH), Oxidized Glutathione (GSSG), Tumor Necrosis Factor-α (TNF-α), Malonaldehyde- (MDA) and 4-hydroxy-2,3-nonenal- (HNE) protein plasma adducts were performed. A significant increase in the GSSG was observed in patients with FS when compared to non-frail. No difference was shown in the GSH amount, suggesting a glutathione oxidation more than impairment of the synthesis. TNF-α, MDA- and HNE- adducts, were significantly higher in FS as compared to non-frail patients. A logistic regression model correlating FS with redox balance showed a close relationship between glutathione ratio (OR= 1.8, 95% CI=1.2–2.5) and MDA adducts (OR= 2.8, 95% CI= 1.6–4.7) to frailty. Our findings show an association between oxidative imbalance and Frailty Syndrome. GSSG/GSH ratio and plasma protein adducts strongly predict the frailty conditions and seem to be reliable and easily measurable markers in the context of the multidimensional analysis of elderly patients.
Chronic sickle cell lung disease: new insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension

Pulmonary hypertension is a common complication of sickle cell disease (SCD). In spite of the mild elevations in pulmonary artery pressures in these patients, the associated morbidity and mortality is high. In fact, in adult patients with SCD, pulmonary hypertension is emerging as the major independent risk factor for death. The aetiology of pulmonary hypertension is probably multifactorial, including haemolysis, impaired nitric oxide bioavailability, chronic hypoxaemia, thromboembolism, parenchymal and vascular injury because of sequestration of sickle erythrocytes, chronic liver disease and asplenia. Interestingly, pulmonary hypertension is emerging as a common, and probably, invariant sequella of lifelong haemolytic anaemia in other hereditary and acquired haemolytic diseases, such as thalassaemia, stomatocytosis and spherocytosis. There are currently limited specific data on the effects of any treatment modality for pulmonary hypertension in patients with SCD. It is likely that maximization of SCD therapy, in all patients, and treatment with selective pulmonary vasodilators and antiproliferative agents, in patients with severe disease, would be beneficial. A large trial evaluating the effects of therapy for pulmonary hypertension in the SCD population is clearly indicated.
Review article: efficacy of infliximab in Crohn’s disease — induction and maintenance of remission

The primary goals of treating patients with Crohn’s disease are to induce a clinical remission, maintain the remission, and prevent associated complications. Various treatment regimens for patients with Crohn’s disease induce a response and remission; however, most prove ineffective for maintenance of the clinical effect. A therapeutic agent that can induce and maintain remission, while promoting the restoration of intestinal mucosa, would prove to be most beneficial in such a patient population.
The Suggested Physiologic Aryl Hydrocarbon Receptor Activator and Cytochrome P4501 Substrate 6-Formylindolo[3,2-b]carbazole Is Present in Humans*

Dioxins and other polycyclic aromatic compounds formed during the combustion of waste and fossil fuels represent a risk to human health, as well as to the well being of our environment. Compounds of this nature exert carcinogenic and endocrine-disrupting effects in experimental animals by binding to the orphan aryl hydrocarbon receptor (AhR). Understanding the mechanism of action of these pollutants, as well as the physiological role(s) of the AhR, requires identification of the endogenous ligand(s) of this receptor. We reported earlier that activation of AhR by ultraviolet radiation is mediated by the chromophoric amino acid tryptophan (Trp), and we suggested that a new class of compounds derived from Trp, in particular 6-formylindolo[3,2-b]carbazole (FICZ), acts as natural high affinity ligands for this receptor. Here we describe seven new FICZ-derived indolo[3,2-b]carbazole-6-carboxylic acid metabolites and two sulfoconjugates, and we demonstrate the following. (i) FICZ is formed efficiently by photolysis of Trp upon exposure to visible light. (ii) FICZ is an exceptionally good substrate for cytochromes P450 (CYP) 1A1, 1A2, and 1B1, and its hydroxylated metabolites are remarkably good substrates for the sulfotransferases (SULTs) 1A1, 1A2, 1B1, and 1E1. Finally, (iii) sulfoconjugates of phenolic metabolites of FICZ are present in human urine. Our findings indicate that formylindolo[3,2-b]carbazols are the most potent naturally occurring activators of the AhR signaling pathway and may be the key substrates of the CYP1 and SULT1 families of enzymes. These conclusions contradict the widespread view that xenobiotic compounds are the major AhR ligands and CYP1 substrates.
A Study of Lipid Profile in Type 2 Diabetic Punjabi Population

Dyslipidemia is one of the major cardiovascular disease (CVD) risk factors and plays an important role in the progress of atherosclerosis, the underlying pathology of CVD. The prevalence of dyslipidemia in type 2 diabetes is double with respect to the general population (Haffner, 1998). These are more complex abnormalities that are caused by the interrelation among obesity, insulin resistance and hyperinsulinism (Burstein et al., 1970 & American Diabetes Association, 1998). According to Freedman et al (1999), when the overweight subjects were compared with their respective thinner counterparts, they presented 2.4 to 7.1 times higher probability to have an elevated total cholesterol, LDL cholesterol, triglycerides and blood pressure as well as 12.6 times higher probability to have hyperinsulinemia. It is worth to emphasize that the fatty tissue is exclusively related to risk factors, such as the altered insulin and lipid profile, which can contribute to the development of the insulin resistance syndrome, which comprises several risk factors for the emergence of cardiovascular complications (Gower, 1999). In patients with type 2 diabetes, which is equivalent to CHD (Juutilainen et al, 2005), it is most commonly characterized by elevated TG and reduced HDL-C (Goldberg 2001). These abnormalities can be present alone or in combination with other metabolic disorders. The prevalence of dyslipidaemia varies depending on the Abstract
Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Introduction to Genetics and Childhood Obesity: Relevance to Nursing Practice

Purpose: The aims for this article are to provide an overview of the current state of research on genetic contributions to the development of childhood obesity and to suggest genetic-focused nursing practices to prevent childhood obesity. Organizing Constructs: Genetic epidemiology of childhood obesity, modes to identifying obesity genes, types of human obesity genes, and nursing implications are discussed. Clinical Relevance: The successful integration of genetics into nursing practice will provide opportunities for nurses to participate fully as major agents and collaborators in the health care revolution. Conclusions: Practicing nurses across the profession will need to become knowledgeable about genetics and take part in obesity prevention through genetic assessment of susceptibility and appropriate environmental interventions.
Food allergy in fully breast‐fed infants

Introduction It is widely accepted that potentially allergenic macro-molecules are absorbed by the normal adult gut (Lancet, 1978) and may pass from mother to infant in breast milk (Matsumura et al, 1975). Several decades ago physicians realized that such substances could produce adverse reactions in susceptible infants (Shannon, l921;Talbot, 1918). and more recently have suggested that they can cause infantile colic (IUingworth. 1954), vomiting, diarrhoea, eczema, asthma and rhinorrhoea (Glaser, 1956). Unfortunately, the reports are anecdotal and rely on unsubstantiated information -from parents. This paper presents two infants with allergic reactions to extrinsic food antigens transmitted in their mothers breast milk and suggests a method of evaluating the phenomenon objectively.