Biogenic Amine-Stimulated Cyclic Adenosine-3'',5''-Monophosphate Formation in the Rat Carotid Body

The subcutaneous injection of isoprenaline, salbutamol, histamine, and adrenaline to rats, which were subsequently killed by microwave irradiation, resulted in a rapid increase in the cyclic AMP content of the carotid body. On the other hand, noradrenaline, dopamine, adenosine, and 5-hydroxytryptamine, at doses at least 100 times greater than that of isoprenaline, did not significantly alter the cyclic nucleotide content in vivo. The response to isoprenaline was dose related, with an ED50 of 15 micrograms X kg-1, and reached a peak level 1-1.5 min after injection. Incubation of intact carotid bodies with isoprenaline (10(-5) M) in vitro also resulted in a 10-fold increase in cyclic AMP content. The in vivo response to isoprenaline could be blocked stereo-selectively by propranolol, and ICI 118.551, a beta 2-selective antagonist, blocks the isoprenaline-elicited increase in cyclic AMP completely at a dose of 30 micrograms X kg-1; whereas betaxolol, a beta 1-selective antagonist, was ineffective, even at a dose of 300 micrograms X kg-1. Hypoxia (5% oxygen in 95% N2) did not result in a significant increase in the cyclic AMP content, nor did it significantly alter the isoprenaline-stimulated increase in the cyclic AMP content of the rat carotid body. These results suggest that some catecholamines may stimulate cyclic AMP formation by interacting with a beta 2-adrenoceptor in the rat carotid body.     

Centriole maturation in the amoebae ofPhysarum polycephalum

Summary The precise geometry of pro-centriole formation has been studied inPhysarum polycephalum amoebae. The spatial references used were the posterior and the anterior kinetosomes which are unequivocally defined by the presence of the posterior para-kinetosomal structure, the microtubular array 4 and the microtubular arrays 1, 2, and 3. The observations made suggest that pro-centrioles follow a maturation process. A pro-centriole formed during the n^th cell cycle becomes the posterior kinetosome during the (n + 1)^th cell cycle and the anterior one during all the following cell cycles. Pro-centriole formation occurs late in the cell cycle. This observation disagrees with a role of pro-centriole formation in the regulation of S phase in contrast to what has been suggested in other eucaryotic cells.     

A robust fuzzy stochastic programming model for the design of a reliable green closed-loop supply chain network

Recently, governmental legislations, limitation of natural resources and adverse effects of End-of-Life products on ecological system have spurred researchers to design closed-loop supply chains (CLSCs). Accordingly, designing green supply chains (SCs) that manage greenhouse gas emissions and prevent air pollution can be helpful for companies to heighten profitability and customer loyalty, besides, uncertainty of parameters and disruption strikes could adversely affect performance of SCs and lower quality of output decisions. Effective planning prevents great losses and increases reliability of manager's decisions against uncertainties. Therefore, this paper is proceeding to design a reliable bi-objective green CLSC that minimizes total costs of network aside with minimizing harmful gas emissions. The proposed model is capable of controlling adverse effects of disruptions via applying scenario-based stochastic programming approach. Also, an effective hybrid robust fuzzy stochastic programming method is extended to effectively control uncertainty of parameters and risk-aversion level of output decisions. Extended model analyzing is based on lead-acid battery SC case study that output results approve applicability and effectiveness of model.     

Embryonic Lethality in Homozygous Human Her-2 Transgenic Mice Due to Disruption of the Pds5b Gene

The development of antigen-targeted therapeutics is dependent on the preferential expression of tumor-associated antigens (TAA) at targetable levels on the tumor. Tumor-associated antigens can be generated de novo or can arise from altered expression of normal basal proteins, such as the up-regulation of human epidermal growth factor receptor 2 (Her2/ErbB2). To properly assess the development of Her2 therapeutics in an immune tolerant model, we previously generated a transgenic mouse model in which expression of the human Her2 protein was present in both the brain and mammary tissue. This mouse model has facilitated the development of Her2 targeted therapies in a clinically relevant and suitable model. While heterozygous Her2^+/- mice appear to develop in a similar manner to wild type mice (Her2^-/-), it has proven difficult to generate homozygous Her2^+/+ mice, potentially due to embryonic lethality. In this study, we performed whole genome sequencing to determine if the integration site of the Her2 transgene was responsible for this lethality. Indeed, we report that the Her2 transgene had integrated into the Pds5b (precocious dissociation of sisters) gene on chromosome 5, as a 162 copy concatemer. Furthermore, our findings demonstrate that Her2^+/+ mice, similar to Pds5b^-/- mice, are embryonic lethal and confirm the necessity for Pds5b in embryonic development. This study confirms the value of whole genome sequencing in determining the integration site of transgenes to gain insight into associated phenotypes.     

Mortality,Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort

Introduction

Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013.

Materials and Methods

We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models.

Mortality Results

182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0–16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7–6.1/1000 py), external was lower [1.7/1000 py; (1.0–2.4/1000 py)].

Survival Results

Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5–7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3–5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4–1.7) and heterosexual female (sHR:2.8; CI:1.1–7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7–123.2) and heterosexual male (sHR:11.8; CI:2.5–56.4) versus MSM.

Conclusion and Recommendation

There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.     

A Penalized-Likelihood Method to Estimate the Distribution of Selection Coefficients from Phylogenetic Data

We develop a maximum penalized-likelihood (MPL) method to estimate the fitnesses of amino acids and the distribution of selection coefficients (S = 2Ns) in protein-coding genes from phylogenetic data. This improves on a previous maximum-likelihood method. Various penalty functions are used to penalize extreme estimates of the fitnesses, thus correcting overfitting by the previous method. Using a combination of computer simulation and real data analysis, we evaluate the effect of the various penalties on the estimation of the fitnesses and the distribution of S. We show the new method regularizes the estimates of the fitnesses for small, relatively uninformative data sets, but it can still recover the large proportion of deleterious mutations when present in simulated data. Computer simulations indicate that as the number of taxa in the phylogeny or the level of sequence divergence increases, the distribution of S can be more accurately estimated. Furthermore, the strength of the penalty can be varied to study how informative a particular data set is about the distribution of S. We analyze three protein-coding genes (the chloroplast rubisco protein, mammal mitochondrial proteins, and an influenza virus polymerase) and show the new method recovers a large proportion of deleterious mutations in these data, even under strong penalties, confirming the distribution of S is bimodal in these real data. We recommend the use of the new MPL approach for the estimation of the distribution of S in species phylogenies of protein-coding genes.     

Isolation and characterization of enteroaggregative,enterotoxigenic, diffusely adherent <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Salmonella</Emphasis> Worthington from human diarrhoeic faecal samples in Kashmir and Secunderabad,India

Seven hundred and thirty-five diarrhoeic faecal samples from children were investigated for presence of enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), diffusely adherent E. coli (DAEC) and Salmonella spp. by polymerase chain reaction (PCR) and bacterial culture. Out of 675 samples from Kashmir, 55 isolates were obtained, which carried at least one virulence gene studied. Out of the 55 isolates, 36 (65.45%) were EAEC, 18 (32.72%) were ETEC while only one isolate (1.81%) was DAEC. All the EAEC isolates were found to be typical as they possessed aggR gene. Six (16.66%) EAEC isolates carried the astA gene. Out of the 18 ETEC isolates, 13 carried the elt gene alone, four possessed both the elt and est genes and the remaining one harboured the est gene alone. Five ETEC isolates also possessed astA gene. Nineteen EAEC isolates belonged to 10 different serogroups. Serogroup O153 was most frequent. The ETEC isolates also belonged to 10 different serogroups of which O159 was most predominant. Out of 224 E. coli isolates from 60 samples of Secunderabad, 27 isolates carried at least one virulence gene. Out of 27 isolates 22 (81.48%) were typical EAEC, three (11.11%) were ETEC and two (7.4%) were DAEC. Fifteen EAEC isolates belonged to seven different serogroups with O86 as most frequent. Four EAEC isolates also possessed the astA gene. All the three ETEC isolates harboured elt gene only and belonged to three different serogroups. Two isolates of Salmonella Worthington were obtained from only two samples in Kashmir.