Filtering high-throughput protein-protein interaction data using a combination of genomic features

Background  

Protein-protein interaction data used in the creation or prediction of molecular networks is usually obtained from large scale or high-throughput experiments. This experimental data is liable to contain a large number of spurious interactions. Hence, there is a need to validate the interactions and filter out the incorrect data before using them in prediction studies.     

TORCs rev up gluconeogenesis

Transducer of regulated CREB activity (TORC) proteins promote transactivation by the cAMP response element binding protein (CREB) and mediate effects of cAMP agonists on gene expression. Koo et al. now report that TORC phosphorylation and nuclear/cytoplasmic shuttling play a key role in the regulation of gluconeogenesis by cAMP. Control of TORC phosphorylation and function may integrate the effects of multiple factors involved in metabolic control, including cAMP agonists, insulin, and AMP kinases. TORCs, and kinases affecting TORC function, are promising new therapeutic targets for the treatment of diabetes mellitus.     

Antimalarial and antileishmanial activities of histone deacetylase inhibitors with triazole-linked cap group

Histone deacetylase inhibitors (HDACi) are endowed with plethora of biological functions including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. Parsing the structure–activity relationship (SAR) for each disease condition is vital for long-term therapeutic applications of HDACi. We report in the present study specific cap group substitution patterns and spacer-group chain lengths that enhance the antimalarial and antileishmanial activity of aryltriazolylhydroxamates-based HDACi. We identified many compounds that are several folds selectively cytotoxic to the plasmodium parasites compared to standard HDACi. Also, a few of these compounds have antileishmanial activity that rivals that of miltefosine, the only currently available oral agent against visceral leishmaniasis. The anti-parasite properties of several of these compounds tracked well with their anti-HDAC activities. The results presented here provide further evidence on the suitability of HDAC inhibition as a viable therapeutic option to curb infections caused by apicomplexan protozoans and trypanosomatids.     

A QSAR study on some series of anti-hepatitis B virus (HBV) agents

A quantitative structure-activity relationship (QSAR) study has been made on some series of anti-hepatitis B virus (HBV) agents, namely, a series of novel bis(L-amino acid) ester prodrugs of 9-[2--(phosphonomethoxy)ethyl]adenine, a similar series of compounds comprising of 2- amino-6-arylthio-9-[2-(phosphonoethoxy)ethyl] purine bis(2,2,2- trifluoroethyl) esters, and a series of 1-isopropylsulfonyl-2-amine benzimidazoles. In each case significant correlations are found between the anti-HBV potencies and some physicochemical and steric properties of the compounds, indicating that for the first two series the activity is controlled by the hydrophobic and the bulk properties of the molecules and, for the third series, the steric and hydrogen bonding properties of compounds are crucial for their anti-HBV potency.     

Bonding acrylic teeth to acrylic resin denture bases: a review

Partial or complete dentures are more commonly constructed for the elderly group of the population. Teeth debonding from the dentures can be frustrating to the patients as well as the dentist. Research has been carried out and is continuing to study the issue of bonding acrylic teeth to the denture base resin. The present review takes into account the majority of research papers published in the last five decades for determining the bond strength. Selection of more compatible combinations of denture base resins and acrylic teeth may reduce the number of prosthesis fractures and the resultant repairs.     

Understanding women’s burdens: preliminary findings on psychosocial health among datoga and iraqw women of northern tanzania

This preliminary, community-based study examines major stressors identified by Iraqw and Datoga women of Mbulu District, Tanzania, and describes steps in creating a culturally specific questionnaire to assess mental health burdens. This area of Tanzania is remote, with limited access to goods and services, and is undergoing dramatic social and economic changes. Iraqw and Datoga reside in close proximity and often intermarry but have different cultural and subsistence responses to this rapid social change. Data were collected from May to October 2002, with 49 Datoga women and 64 Iraqw women interviewed. In-home interviews were conducted to have women (1) free-list their primary concerns and (2) answer questions from a translated (in Datoga and Iraqw) and modified standardized mental health questionnaire. Both groups of women identified hunger, the lack of animals, particularly cattle, and health/illnesses as the most common major stressors. Other frequently cited stressors included crop failure, general fears of violence, paying taxes, and no money for basic needs. Additional refinements are required for the mental health questionnaire, with strengths and limitations discussed. Such data, while preliminary, augment efforts to analyze the emotional burdens associated with dramatic social change.     

RhoA- and PKC-alpha-mediated phosphorylation of MYPT and its association with HSP27 in colonic smooth muscle cells

Agonist-induced activation of the RhoA/Rho kinase (ROCK) pathway results in inhibition of myosin phosphatase and maintenance of myosin light chain (MLC20) phosphorylation. We have shown that RhoA/ROCKII translocates and associates with heat shock protein (HSP)27 in the particulate fraction. We hypothesize that inhibition of the 130-kDa regulatory myosin-binding subunit (MYPT) requires its association with HSP27 in the particulate fraction. Furthermore, it is not certain whether regulation of MYPT by CPI-17 or by ROCKII is due to cross talk between RhoA and PKC-alpha. Presently, we examined the cross talk between RhoA and PKC-alpha in the regulation of MYPT phosphorylation in rabbit colon smooth muscle cells. Acetylcholine induced 1) sustained phosphorylation of PKC-alpha, CPI-17, and MYPT; 2) an increase in the association of phospho-MYPT with HSP27 in the particulate fraction; 3) a decrease in myosin phosphatase activity (66.21+/-3.52 and 42.19+/-3.85% nM/ml lysate at 30 s and 4 min); and 4) an increase in PKC activity (298.12+/-46.60% and 290.59+/-22.07% at 30 s and 4 min). Inhibition of RhoA/ROCKII by Y-27632 inhibited phosphorylation of MYPT and its association with HSP27. Both Y27632 and a negative dominant construct of RhoA inhibited phosphorylation of MYPT and CPI-17. Inhibition of PKCs or calphostin C or selective inhibition of PKC-alpha by negative dominant constructs inhibited phosphorylation of MYPT and CPI-17. The results suggest that 1) acetylcholine induces activation of both RhoA and/or PKC-alpha pathways, suggesting cross talk between RhoA and PKC-alpha resulting in phosphorylation of MYPT, inhibition of myosin phosphatase activity, and maintenance of MLC phosphorylation; and 2) phosphorylated MYPT is associated with HSP27 and translocated to the particulate fraction, suggesting a scaffolding role for HSP27 in mediating the association of the complex MYPT/RhoA-ROCKII. Thus both pathways (PKC and RhoA) converge on the regulation of myosin phosphatase activities and modulate sustained phosphorylation of MLC20.     

Production of lactic acid and fructose from media with cane sugar using mutant of Lactobacillus delbrueckii NCIM 2365

AIMS: To examine the potential of Lactobacillus delbrueckii mutant, Uc-3 to produce lactic acid and fructose from sucrose-based media. METHODS AND RESULTS: The mutant of L. delbrueckii NCIM 2365 was cultivated in shake flask containing hydrolysed cane sugar (sucrose)-based medium. The lactic acid yield and volumetric productivity with hydrolysed cane concentration up to 200 g l(-1) were in the range of 92-97% of the theoretical value and between 2.7 and 3.8 g l(-1) h(-1), respectively. The fructose fraction of the syrup produced was more than 95% when the total initial sugar concentration in the medium was higher (150-200 g l(-1)). There are no unwanted byproducts detected in the fermentation broth. CONCLUSIONS: We demonstrated that L. delbrueckii mutant Uc-3 was able to utilize glucose preferentially to produce lactic acid and fructose from hydrolysed cane sugar in batch fermentation process. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings will be useful in the production of lactic acid and high fructose syrups using media with high concentrations of sucrose-based raw materials. This approach can lead to modification of the traditional fermentation processes to obtain value-added byproducts, attaining better process economics.