Computational Investigation of Protein Assemblies

Selective nitrosylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) at Cys-247 affects gene regulation through the interferon-gamma (IFN- γ) activated inhibitor of translation (GAIT) complex. Oxidized low-density lipoprotein (LDLox) and INF-γ induce assembly of the nitrosylase complex composed of inducible nitric oxide synthase (iNOS), S100A8, and S100A9 proteins. Crystal structure of the complex of GAPDH and S100A8A9 is not known, structural prediction method were employed by protein-protein docking and binding energy calculation with PatchDock and FIREDock respectively. Candidate models were selected, based on a weight factor calculated, from the computational method developed from the artificial protease cleavage mapping Fe(III) (s)-1-(p- bromoacetamidobenzyl) EDTA to identify helical domains of GAPDH that may interact with S100A8. Models were also selected based on the Boltzmann distribution according to their binding energy. Interface residue analysis suggest that from the models that matched with experimental data, DCE-9 has highest weight factor of 1.68. Docking complexes without experimental bias has the highest binding energy of -76.04 kcal/mol when compared to other candidate models. Our analysis also suggests that complex that matched with experimental data are less likely to form as their binding energies were much lower when compared to the models that were not selected based on experimental data. It can be inferred from our analysis that artificial cleavage mapping may lead to artefacts and the CHARMM19 force field used in FIREDock may not accurately represent the true binding energy of these complexes

Strategic Institutional Capacity in Solid Waste Management: The cases of Dhaka North and South City Corporations in Bangladesh

Tutkimus analysoi jätehuollon strategista ja institutionaalista kapasiteettia Bangladeshin pääkaupungissa Dhakassa. Tämä aihe on siitä tehtyjen tutkimusten mukaan lähes kaikissa kehittyvissä maissa vakavissa ongelmissa. Dhaka tarjoaa hedelmällisen maaperän tutkia jätehuollon hallinnollisia ja johtamistaidollisia ongelmia. Jokaisessa organisaatiossa tarvitaan strategista johtamista, pitkää aikatähtäintä ja päätöksentekokykyä järjestää toimivat palvelut. Näin on myös jätehuollossa suurissa urbanisoituneissa kaupungeissa. Strategisella johtamisella on oltava institutionaalista kapasiteettia, jotta sen avulla varmistetaan jätehuollon menestys tehokkuutena ja vaikuttavuutena. Strategisen johtamisen kapasiteettiin luetaan kuuluviksi tehokkaat prosessit, toimivat järjestelmät ja riittävät resurssit. Näitä kapasiteetteja tulisi ehdottomasti lisätä Dhakan jätehuollossa. Tämä tutkimus keskittyy analysoimaan näiden tekijöiden merkitystä Dhakan jätehuollon strategisessa johtamisessa. Se avaa samalla näkökulman muihin kehitysmaihin, jotka kamppailevat jätehuollon strategisen johtamisen ongelmien kanssa. Tutkimus on luonteeltaan laadullinen. Se tarkastelee jätehuollosta vastaavien käsityksiä alansa strategisesta kapasiteetista ja sen eri ulottuvuuksista. Tätä varten haastateltiin 32 strategisesta johdosta vastaavaa jätehuollon ammattilaista Dhakassa. Haastattelut osoittivat, että jätehuollon strategisessa kapasiteetissa on vakavia puutteita. Päättäjät eivät riittävästi ymmärrä strategisen johtamisen asemaa ja roolia jätehuollon kehittämisessä. Strategisten tavoitteiden muotoilu ja toteuttaminen ovat vaikeasti hallittavia prosesseja. Dhakan keskushallinto vaikeuttaa valinnoillaan jätehuollon strategista ajattelua ja hyvien käytäntöjen hyödyntäminen on sattumanvaraista. Tutkimus osoittaa, että Dhakassa, ja myös muiden kehitysmaiden suurissa kaupungeissa, tarvitaan vahvaa strategista kapasiteettia; suhteellisen itsenäistä hallinnollista asemaa, ennakkoluulotonta ajattelua ja johdonmukaista toimintaa. Tutkimuksen mukaan mm. nämä tekijät takaavat toimivat jätehuollon palvelut.The study analyses strategic institutional capacity related to solid waste management in Dhaka, Bangladesh. It finds that Dhaka city lacks institutional capacity regarding solid waste management and governance is in a state of crisis. It investigates these institutional and governance failures and proposes measures to overcome them. Strategic capacity is fundamental for any organization. The success, effectiveness and efficiency of management and governance depends on strategic capacity. The concept refers to the ability to make and institutionalise long-term strategic decisions and trajectories. In the Dhaka case, a lack of proper organizational capacity is notably apparent regarding solid waste management. The study argues that strategic capacity should be increased to deploy available resources, while governance processes and systems should be designed in a more appropriate manner. The scientific objective of the study is to contribute descriptive and interpretative knowledge to the theory and literature of strategic capacity and solid waste-management policy analysis. The practical objective is to understand and analyze strategic institutional capacity building in the Bangladeshi context. The study does not follow any particular theory. It is nevertheless grounded on relevant concepts and theories that conceptualize the research phenomena and develop the conceptual framework. It uses qualitative research methods utilizing a constructivist approach. For data collection, the study interviewed 32 respondents from multiple levels of the Bangladeshi bureaucracy. These were broken down in into categories: the strategic apex, middle-line and techno-structure. Findings were analysed thematically using an inductive approach. The study found that strategic institutional capacity and governance in general in the corporations of Dhaka City is weak. This is particularly true in the case solid waste management. A key finding is that City Corporations in Dhaka lack a proper understanding of the role of strategic capacity in improving governance and institutional capacity. The major thematic analysis concludes; (i) The predominant strategic perspective is inappropriate relative to policy goals; (ii) Current practices are not based on local needs, but on central government influence and bureaucratic guidance; (iii) Good governance practices and institutional capacity-building is not sufficiently emphasized; as a result, (iv) Solid waste management is ineffective. The study recommended that an appropriate strategic perspective should be encouraged in DCCs for effective governance and better solid waste services. Democratic governance practices, sectoral specific strategies, governance coordination policy, resource based plan and cooperative working relation with central government may expedite the appropriate strategic perspective in DCCs. In the long-run, a realistic strategic perspective will increase strategic capacity as a whole and improve institutional capacity as well. While the study specifically focuses on Dhaka city, it nevertheless has important implications for understanding solid-waste management governance practices in the developing world in general

P20-08. Glycosylation: an important factor in Env diversity

Supported by a CAVD Grant from the Bill and Melinda Gates Foundation

Antidiabetic potential of Moringa oleifera Lam. leaf extract in type 2 diabetic rats, and its mechanism of action

Purpose: To explore the antidiabetic potential of Moringa oleifera leaf extract in type 2 diabetic rats, and the underlying mechanisms.Methods: Streptozotocin (STZ) at a dose of 40 mg/kg was given to high fat diet (HFD)- fed rats to induce type 2 diabetes. M. oleifera leaf extract at doses 100, 200 and 400 mg/kg were given to 3 groups of type 2 diabetic rats. The area under curve (AUC) of glucose and homeostasis model assessment of insulin resistance (HOMA-R) were calculated using appropriate formulas, whereas levels of glucose,insulin, peroxisome proliferator activated receptor-γ (PPARγ, dipeptidyl peptidase-IV (DPP-IV) and inflammatory cytokines (IL-6, IL-1β and TNFα) were assayed using ELISA kits.Results: The leaf extract of M. oleifera significantly reduced the levels of glucose, insulin and cytokines in treated type 2 diabetic groups (p < 0.05). DC group had significantly increased AUC for glucose, whereas the extract-treated groups showed significant  decrease in glucose AUC. There was significant decrease in insulin sensitivity parameters, as indicated by increase in HOMA-R and decrease in PPARγ levels in the DC group (p < 0.05). However, treatment with the M. oleifera extract reversed this trend via marked decrease in HOMA-R level and significant rise in PPARγ level. In contrast, the extract had no effect on DPP-IV concentration in diabetic treated groups (p < 0.05).Conclusion: These results indicate that M. oleifera leaf extract mitigates hyperglycemia in type 2 DM by modulating hyperinsulinemia, PPARγ and inflammatory cytokines. Thus, the extract is a potential source of drug for the management of type 2 DM. Keywords: Moringa oleifera, Diabetes mellitus, Streptozotocin, Peroxisome proliferator activated receptor-γ, Dipeptidyl peptidase I

Protein Shape Sampled by Ion Mobility Mass Spectrometry Consistently Improves Protein Structure Prediction

Ion mobility (IM) mass spectrometry provides structural information about protein shape and size in the form of an orientationally-averaged collision cross-section (CCSIM). While IM data have been used with various computational methods, they have not yet been utilized to predict monomeric protein structure from sequence. Here, we show that IM data can significantly improve protein structure determination using the modelling suite Rosetta. We develop the Rosetta Projection Approximation using Rough Circular Shapes (PARCS) algorithm that allows for fast and accurate prediction of CCSIM from structure. Following successful testing of the PARCS algorithm, we use an integrative modelling approach to utilize IM data for protein structure prediction. Additionally, we propose a confidence metric that identifies near native models in the absence of a known structure. The results of this study demonstrate the ability of IM data to consistently improve protein structure prediction

British Colonialism and the Criminalization of Homosexuality

What explains the global variation in laws criminalizing homosexual conduct? Recent research has claimed that British colonialism is largely responsible for the criminalization of homosexuality around the world. This article utilizes a newly constructed dataset that includes up-to-date data on 185 countries to assess this claim. We find that British colonies are much more likely to have criminalization of homosexual conduct laws than other colonies or other states in general. This result holds after controlling for other variables that might be expected to influence the likelihood of repressive lesbian, gay, bisexual and transgender (LGBT) rights legislation. However, we also find that the evidence in favour of the claim that British imperialism ‘poisoned’ societies against homosexuality is weak. British colonies do not systematically take longer to decriminalize homosexual conduct than other European colonies

Population dynamics of rhesus macaques and associated foamy virus in Bangladesh.

Foamy viruses are complex retroviruses that have been shown to be transmitted from nonhuman primates to humans. In Bangladesh, infection with simian foamy virus (SFV) is ubiquitous among rhesus macaques, which come into contact with humans in diverse locations and contexts throughout the country. We analyzed microsatellite DNA from 126 macaques at six sites in Bangladesh in order to characterize geographic patterns of macaque population structure. We also included in this study 38 macaques owned by nomadic people who train them to perform for audiences. PCR was used to analyze a portion of the proviral gag gene from all SFV-positive macaques, and multiple clones were sequenced. Phylogenetic analysis was used to infer long-term patterns of viral transmission. Analyses of SFV gag gene sequences indicated that macaque populations from different areas harbor genetically distinct strains of SFV, suggesting that geographic features such as forest cover play a role in determining the dispersal of macaques and SFV. We also found evidence suggesting that humans traveling the region with performing macaques likely play a role in the translocation of macaques and SFV. Our studies found that individual animals can harbor more than one strain of SFV and that presence of more than one SFV strain is more common among older animals. Some macaques are infected with SFV that appears to be recombinant. These findings paint a more detailed picture of how geographic and sociocultural factors influence the spectrum of simian-borne retroviruses