An adaptive optimal ensemble classifier via bagging and rank aggregation with applications to high dimensional data

Background  

Generally speaking, different classifiers tend to work well for certain types of data and conversely, it is usually not known a priori which algorithm will be optimal in any given classification application. In addition, for most classification problems, selecting the best performing classification algorithm amongst a number of competing algorithms is a difficult task for various reasons. As for example, the order of performance may depend on the performance measure employed for such a comparison. In this work, we present a novel adaptive ensemble classifier constructed by combining bagging and rank aggregation that is capable of adaptively changing its performance depending on the type of data that is being classified. The attractive feature of the proposed classifier is its multi-objective nature where the classification results can be simultaneously optimized with respect to several performance measures, for example, accuracy, sensitivity and specificity. We also show that our somewhat complex strategy has better predictive performance as judged on test samples than a more naive approach that attempts to directly identify the optimal classifier based on the training data performances of the individual classifiers.     

Analysis of extracellular vesicle miRNA profiles in heart failure

Extracellular vesicles (EVs) have recently emerged as an important carrier for various genetic materials including microRNAs (miRs). Growing evidences suggested that several miRs transported by EVs were particularly involved in modulating cardiac function. However, it has remained unclear what miRs are enriched in EVs and play an important role in the pathological condition. Therefore, we established the miR expression profiles in EVs from murine normal and failing hearts and consecutively identified substantially altered miRs. In addition, we have performed bioinformatics approach to predict potential cardiac outcomes through the identification of miR targets. Conclusively, we observed approximately 63% of predicted targets were validated with previous reports. Notably, the predicted targets by this approach were often involved in both beneficial and malicious signalling pathways, which may reflect heterogeneous cellular origins of EVs in tissues. Lastly, there has been an active debate on U6 whether it is a proper control. Through further analysis of EV miR profiles, miR‐676 was identified as a superior reference control due to its consistent and abundant expressions. In summary, our results contribute to identifying specific EV miRs for the potential therapeutic targets in heart failure and suggest that miR‐676 as a new reference control for the EV miR studies.     

Bioremediation of hexavalent chromium from wastewater using bacteria-a green technology

Biodegradation - Hexavalent chromium has high toxic effect on the ecological system. The aim of the present study is to isolate and characterize the bacteria that can reduce the toxicity of...     

Destabilization of the Epidermal Growth Factor Receptor (EGFR) by a Peptide That Inhibits EGFR Binding to Heat Shock Protein 90 and Receptor Dimerization

An eight-amino acid segment is known to be responsible for the marked difference in the rates of degradation of the EGF receptor (ErbB1) and ErbB2 upon treatment of cells with the Hsp90 inhibitor geldanamycin. We have scrambled the first six amino acids of this segment of the EGF receptor (EGFR), which lies in close association with the ATP binding cleft and the dimerization face. Scrambling these six amino acids markedly reduces EGFR stability, EGF-stimulated receptor dimerization, and autophosphorylation activity. Two peptides were synthesized as follows: one containing the wild-type sequence of the eight-amino acid segment, which we call Disruptin; and one with the scrambled sequence. Disruptin inhibits Hsp90 binding to the EGFR and causes slow degradation of the EGFR in two EGFR-dependent cancer cell lines, whereas the scrambled peptide is inactive. This effect is specific for EGFR versus other Hsp90 client proteins. In the presence of EGF, Disruptin, but not the scrambled peptide, inhibits EGFR dimerization and causes rapid degradation of the EGFR. In contrast to the Hsp90 inhibitor geldanamycin, Disruptin inhibits cancer cell growth by a nonapoptotic mechanism. Disruptin provides proof of concept for the development of a new class of anti-tumor drugs that specifically cause EGFR degradation.     

Cloning, characterization and expression of a chloroplastic fructose-1,6-bisphosphatase from Porteresia coarctata conferring salt-tolerance in transgenic tobacco

A gene coding for the chloroplastic fructose 1,6-bisphosphatase (PcCFR) in Porteresia coarctata Tateoka (Roxb.), a halophytic wild rice, has been isolated along with its rice (Oryza sativa; var. indica) homologue (OsCFR), cloned and sequenced. Comparison between the nucleotide and deduced amino acid sequences of these two revealed a difference in five amino acid residues, namely Glu¹⁴, Thr²⁴, Ala⁴⁸, Ala¹⁶³ and Arg²⁹⁶ in OsCFR which have been found to be replaced by Ser¹⁴, Ile²⁴, Ser⁴⁸, Ser¹⁶³ and Lys²⁹⁶ in PcCFR respectively. The purified recombinant PcCFR is found to retain its enzymatic activity in presence of up to 500 mM NaCl in vitro as opposed to OsCFR, which is inactivated even at lower salt concentration. The six in vitro point mutant proteins of PcCFR showed varied degree of sensitivity towards high salt, with the maximum OsCFR-like effect in the triple mutant S¹⁴A-S⁴⁸A-S¹⁶³A suggesting a possible concerted role of all three serine residues in the in vitro salt tolerance property of PcCFR protein. Transgenic tobacco plants with chloroplast targeted PcCFR and OsCFR gene(s) have been developed under constitutive expression of CaMV 35S promoter and NOS terminator. The PcCFR transgenics showed better plant growth during exposure to salt stress in comparison to either the OsCFR or the empty vector transformed plants. The PcCFR transgenics also revealed enhanced photosynthetic efficiency coupled with protection to both photodamage of PSII and chlorophyll degradation through better reactive oxygen species scavenging at higher concentration of NaCl during late salt-stress growth.     

Chronic cold stress-induced alterations in brush border membrane composition and enzyme activities in rat intestine

The effect of chronic cold stress on the composition and function of rat intestinal brush border membrane (BBM) was studied. Various lipid fractions from intestinal BBM viz. cholesterol (p < 0.01), phospholipids (p < 0.01), triglycerides (p < 0.05) and gangliosides (p < 0.05) were significantly reduced in cold stressed animals, as compared to controls. Analysis of membrane saccharide content revealed a significant increase in sialic acid (25%) and hexosamine (36%) contents and a reduction in fucose (19%) content in cold stressed rats. Determination of various enzyme activities in BBM showed significantly enhanced activities of alkaline phosphatase ( p < 0.01), lactase ( p < 0.001) and leucine aminopeptidase ( p < 0.001), whereas sucrase activity was reduced ( p < 0.05) under these conditions. The magnitude and site of these alterations across the crypt-villus axis varied from enzyme to enzyme. These findings suggest that chronic cold stress results in profound alterations in intestinal BBM. Altered structure and function of intestinal BBM may play a role in stress-induced derangements in gastrointestinal tract.     

Age-related oxidative stress compromises endosomal proteostasis

A hallmark of aging is an imbalance between production and clearance of reactive oxygen species and increased levels of oxidatively damaged biomolecules. Herein, we demonstrate that splenic and nodal antigen-presenting cells purified from aging mice accumulate oxidatively modified proteins with side-chain carbonylation, advanced glycation end products, and lipid peroxidation. Furthermore, we show that the endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy-delivered proteins. In support of a causative role for oxidized products in the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens. These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response.     

A bispecific antibody based assay shows potential for detecting tuberculosis in resource constrained laboratory settings

The re-emergence of tuberculosis (TB) as a global public health threat highlights the necessity of rapid, simple and inexpensive point-of-care detection of the disease. Early diagnosis of TB is vital not only for preventing the spread of the disease but also for timely initiation of treatment. The later in turn will reduce the possible emergence of multi-drug resistant strains of Mycobacterium tuberculosis. Lipoarabinomannan (LAM) is an important non-protein antigen of the bacterial cell wall, which is found to be present in different body fluids of infected patients including blood, urine and sputum. We have developed a bispecific monoclonal antibody with predetermined specificities towards the LAM antigen and a reporter molecule horseradish peroxidase (HRPO). The developed antibody was subsequently used to design a simple low cost immunoswab based assay to detect LAM antigen. The limit of detection for spiked synthetic LAM was found to be 5.0 ng/ml (bovine urine), 0.5 ng/ml (rabbit serum) and 0.005 ng/ml (saline) and that for bacterial LAM from M. tuberculosis H37Rv was found to be 0.5 ng/ml (rabbit serum). The assay was evaluated with 21 stored clinical serum samples (14 were positive and 7 were negative in terms of anti-LAM titer). In addition, all 14 positive samples were culture positive. The assay showed 100% specificity and 64% sensitivity (95% confidence interval). In addition to good specificity, the end point could be read visually within two hours of sample collection. The reported assay might be used as a rapid tool for detecting TB in resource constrained laboratory settings.     

Leishmania strains causing self-healing cutaneous leishmaniasis have greater susceptibility towards oxidative stress

The survival of Leishmania parasites within macrophages is influenced by generation of free radicals. To establish whether generation of free radicals influenced chemotherapeutic response, promastigotes from isolates causing self-healing or delayed/non-self-healing cutaneous leishmaniasis (CL) or visceral leishmaniasis (VL) were evaluated for their susceptibility to nitric oxide (NO), antimony and miltefosine. In a self-healing CL strain of Leishmania major (5ASKH), susceptibility to NO and antimony was higher than other species. Likewise, a Leishmania amazonensis strain, M2269, showed greater susceptibility to NO and antimony than other species but no such correlation was observed with miltefosine. Additionally, 5ASKH and M2269 showed poorer free radical scavenging capacity as also their thiol levels were lower than species causing VL. Collectively, our study suggests that self-healing isolates tend to be more susceptible to oxidative stress.