Structure and sequence analyses of Bacteroides proteins BVU_4064 and BF1687 reveal presence of two novel predominantly-beta domains, predicted to be involved in lipid and cell surface interactions.

BackgroundN-terminal domains of BVU_4064 and BF1687 proteins from Bacteroides vulgatus and Bacteroides fragilis respectively are members of the Pfam family PF12985 (DUF3869). Proteins containing a domain from this family can be found in most Bacteroides species and, in large numbers, in all human gut microbiome samples. Both BVU_4064 and BF1687 proteins have a consensus lipobox motif implying they are anchored to the membrane, but their functions are otherwise unknown. The C-terminal half of BVU_4064 is assigned to protein family PF12986 (DUF3870); the equivalent part of BF1687 was unclassified.ResultsCrystal structures of both BVU_4064 and BF1687 proteins, solved at the JCSG center, show strikingly similar three-dimensional structures. The main difference between the two is that the two domains in the BVU_4064 protein are connected by a short linker, as opposed to a longer insertion made of 4 helices placed linearly along with a strand that is added to the C-terminal domain in the BF1687 protein. The N-terminal domain in both proteins, corresponding to the PF12985 (DUF3869) domain is a β-sandwich with pre-albumin-like fold, found in many proteins belonging to the Transthyretin clan of Pfam. The structures of C-terminal domains of both proteins, corresponding to the PF12986 (DUF3870) domain in BVU_4064 protein and an unclassified domain in the BF1687 protein, show significant structural similarity to bacterial pore-forming toxins. A helix in this domain is in an analogous position to a loop connecting the second and third strands in the toxin structures, where this loop is implicated to play a role in the toxin insertion into the host cell membrane. The same helix also points to the groove between the N- and C-terminal domains that are loosely held together by hydrophobic and hydrogen bond interactions. The presence of several conserved residues in this region together with these structural determinants could make it a functionally important region in these proteins.ConclusionsStructural analysis of BVU_4064 and BF1687 points to possible roles in mediating multiple interactions on the cell-surface/extracellular matrix. In particular the N-terminal domain could be involved in adhesive interactions, the C-terminal domain and the inter-domain groove in lipid or carbohydrate interactions

SAGE: Sequential Attribute Generator for Analyzing Glioblastomas using Limited Dataset

While deep learning approaches have shown remarkable performance in many imaging tasks, most of these methods rely on availability of large quantities of data. Medical image data, however, is scarce and fragmented. Generative Adversarial Networks (GANs) have recently been very effective in handling such datasets by generating more data. If the datasets are very small, however, GANs cannot learn the data distribution properly, resulting in less diverse or low-quality results. One such limited dataset is that for the concurrent gain of 19 and 20 chromosomes (19/20 co-gain), a mutation with positive prognostic value in Glioblastomas (GBM). In this paper, we detect imaging biomarkers for the mutation to streamline the extensive and invasive prognosis pipeline. Since this mutation is relatively rare, i.e. small dataset, we propose a novel generative framework - the Sequential Attribute GEnerator (SAGE), that generates detailed tumor imaging features while learning from a limited dataset. Experiments show that not only does SAGE generate high quality tumors when compared to standard Deep Convolutional GAN (DC-GAN) and Wasserstein GAN with Gradient Penalty (WGAN-GP), it also captures the imaging biomarkers accurately

The Impact of Job Stress on Smoking and Quitting: Evidence from the HRS

This paper examines the impact of job-related stress on smoking behavior. We use data from the Health and Retirement Study to examine how high job stress affects the probability that smokers quit and the number of cigarettes smoked for current smokers. We include individual fixed effects, which control for time-invariant factors. Occupational fixed effects are also included to control for occupational characteristics other than stress; time dummies control for the secular decline in smoking rates. Using a sample of people who smoked in the previous wave, we find that job stress is positively related to continuing to smoke and to the number of cigarettes smoked for current smokers. The FE results are of greater magnitude and significance than the OLS results suggesting an important omitted variable bias in OLS estimates. It may be that individuals who are able to handle stress or have better self-control are more likely to have high stress jobs and less likely to smoke. We also find that the smoking/stress relationship is neither explained by heterogeneity across individuals in cognitive ability, risk taking preferences or planning horizons nor is it explained by time varying measures that we observe.

Spindle cell sarcoma of sphenoid bone

Primary bone tumors involving skull are extremely rare and they constitute 0.8% of all bone tumors. The common tumors that are seen in skull base include fibrous dysplasia, giant cell tumor, chordoma, ossifying fibroma, angiosarcoma. We report a rare case of spindle cell sarcoma arising from right sphenoid bone in a 70-year-old male which presented as unilateral defective vision with mild proptosis

Evaluation of adverse drug reactions of first line antiretroviral drugs in a tertiary care centre of Telangana, India

Background: The introduction of highly active anti-retroviral therapy (HAART) has led to a significant reduction in AIDS related morbidity and mortality. Most of the adverse drug reactions are preventable. So continuous evaluation will benefit Antiretroviral treatment that helped to achieve ultimate goal of making treatment safer and more effective to patients. The present study was designed to monitor and analyse the incidence, type and nature of adverse events to first line Antiretroviral drugs.Methods: A cross sectional observational study was conducted at Antiretroviral treatment center of Gandhi Hospital, Secunderabd, Telangana. The study was conducted over a period of 6 months involving all HIV patients. After initiation of 1st line regimen- tenofovir 300mg + lamivudine 300mg + efavirenz 600mg (TLE), patients were followed for any adverse event. Descriptive statistics was used for analysis of data.Results: Out of 453 studied, 47 patients developed adverse events. A total of 79 adverse events were reported. The assessment of total adverse drug reaction profile revealed cutaneous 44.30%, hematological 40.50%, renal 11.39%, gastrointestinal 3.79%. WHO-UMC causality assessment scale showed 76.5% and 23.4% Adverse events as probable and possible respectively. Hartwig and Siegel severity scale revealed 93.6%, 2.1% and 4.3% as mild, moderate and severe cases respectively.Conclusions: The TLE regimen found with lower adverse events in this study. The study focuses the importance of active adverse event monitoring to detect early toxicities and to support safe use of anti-retroviral treatment

Enzymes from Fungal and Plant Origin Required for Chemical Diversification of Insecticidal Loline Alkaloids in Grass-\u3cem\u3eEpichloë\u3c/em\u3e Symbiota

The lolines are a class of bioprotective alkaloids that are produced by Epichloë species, fungal endophytes of grasses. These alkaloids are saturated 1-aminopyrrolizidines with a C2 to C7 ether bridge, and are structurally differentiated by the various modifications of the 1-amino group: -NH2 (norloline), -NHCH3 (loline), -N(CH3)2 (N-methylloline), -N(CH3)Ac (N-acetylloline), -NHAc (N-acetylnorloline), and -N(CH3)CHO (N-formylloline). Other than the LolP cytochrome P450, which is required for conversion of N-methylloline to N-formylloline, the enzymatic steps for loline diversification have not yet been established. Through isotopic labeling, we determined that N-acetylnorloline is the first fully cyclized loline alkaloid, implying that deacetylation, methylation, and acetylation steps are all involved in loline alkaloid diversification. Two genes of the loline alkaloid biosynthesis (LOL) gene cluster, lolN and lolM, were predicted to encode an N-acetamidase (deacetylase) and a methyltransferase, respectively. A knockout strain lacking both lolN and lolM stopped the biosynthesis at N-acetylnorloline, and complementation with the two wild-type genes restored production of N-formylloline and N-acetylloline. These results indicated that lolN and lolM are required in the steps from N-acetylnorloline to other lolines. The function of LolM as an N-methyltransferase was confirmed by its heterologous expression in yeast resulting in conversion of norloline to loline, and of loline to N-methylloline. One of the more abundant lolines, N-acetylloline, was observed in some but not all plants with symbiotic Epichloë siegelii, and when provided with exogenous loline, asymbiotic meadow fescue (Lolium pratense) plants produced N-acetylloline, suggesting that a plant acetyltransferase catalyzes N-acetylloline formation. We conclude that although most loline alkaloid biosynthesis reactions are catalyzed by fungal enzymes, both fungal and plant enzymes are responsible for the chemical diversification steps in symbio

Job Loss: Eat, Drink and Try to be Merry

Preliminary draft. Please do not quote. This paper examines the impact of job loss due to business closings on body mass index (BMI) and alcohol consumption. We suggest that the ambiguous findings in the extant literature may be due in part to unobserved heterogeneity in response and in part due to an overly broad measure of job loss that is partially endogenous (e.g. layoffs). We improve upon this literature by using: exogenously determined business closings, a sophisticated estimation approach (finite mixture models) to deal with complex heterogeneity, and national, longitudinal data from the Health and Retirement Study. For both alcohol consumption and BMI, we find evidence that individuals who are more likely to respond to job loss by increasing unhealthy behaviors are already in the problematic range for these behaviors before losing their jobs. These results suggest the health effects of job loss could be concentrated among “at risk ” individuals and could lead to negative outcomes for the individuals, their families, and society at large

Sin Taxes: Do Heterogeneous Responses Undercut Their Value?

This paper estimates the price elasticity of demand for alcohol using Health and Retirement Survey data. To account for unobserved heterogeneity in price responsiveness, we use finite mixture models. We recover two latent groups, one is significantly responsive to price but the other is unresponsive. Differences between these two groups can be explained in part by the behavioral factors of risk aversion, financial planning horizon, forward looking and locus of control. These results have policy implications. Only a subgroup responds significantly to price. Importantly, the unresponsive group drinks more heavily, suggesting that a higher price could fail to curb drinking by those most likely to cause negative externalities. In contrast, those least likely to impose costs on others are more responsive, thus suffering greater deadweight loss yet with less prevention of negative externalities.

Job Loss: Eat, drink and try to be merry?

This paper examines the impact of job loss from business closings on body mass index (BMI) and alcohol consumption. We improve upon extant literature by using: exogenously determined business closings, a sophisticated estimation approach (finite mixture models) to deal with complex heterogeneity, and national, longitudinal data (Health and Retirement Study). For both alcohol consumption and BMI, we find evidence that individuals who are more likely to respond to job loss by increasing unhealthy behaviors are already in the problematic range for these behaviors before losing their jobs. Thus health effects of job loss could be concentrated among “at risk” individuals.

Evaluation of analgesic activity of irbesartan in albino mice

Background: The objective was to evaluate the analgesic activity of irbesartan in albino mice.Methods: Swiss albino mice weighing 25-30 g of either sex were selected for the study. Six animals were allocated to each experimental group. The control group received normal saline (25 ml/kg, p.o.), standard group received pentazocine (10mg/kg, intraperitonial [i.p.]) and test group received irbesartan (20 mg/kg, p.o.). The above drugs were administered 1 hr prior to the experiments. In case of visceral pain model 0.6% acetic acid was given i.p. 30 mins prior to the experiment to induce writhing, in thermal pain model pretreated mice were placed on Eddy’s Hotplate maintained at 55°C and in mechanical stimulus pain model an artery clip was clamped at the base of the tail of pretreated mice. Decrease in total number of writhes in acetic acid induced writhing model and delay in reaction time in both Eddy’s hot plate and Tail clip method denoted analgesic activity respectively.Results: The test drug significantly decreased the total number of writhes in acetic acid induced writhing model in mice. The percentage inhibition of writhing was significant which was 84.35% in the standard group and 59.24% in the test group. The test drug significantly delayed the reaction time in both Eddy’s hot plate and tail clip method when compared to control group and standard group. Percentage increase in latency period when compared to standard drug was significant and measured 73.11% and 64.31% at 60 min in both Eddy’s hot plate and tail clip method, respectively.Conclusion: Irbesartan exhibits analgesic activity in albino mice