A critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer

Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single gene classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single gene classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single gene classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single gene sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single gene classifiers for predicting outcome in breast cancer

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Impacts of cyclone and flood on crop and fish production in disaster prone coastal Bhola district of Bangladesh

This study assessed the impact of climate change induced disaster on crops and fisheries production at Bhola Sadar and Monpura upazila of Bhola district, Bangladesh during January to June 2018. The study was gathered primary data from primary observation (PO), questionnaire survey (QS), focus group discussion (FGD), and key informant interview (KII). Secondary data were collected from Upazila Agricultural Office and Upazila Fisheries Office of Bhola Sadar and Manpura upazila and moreover, climatic data were collected from Bangladesh Meteorological Department. Results of the study found that trend analysis indicates overall annual maximum temperature increased for Kharif-I, Kharif-II and Rabi season. Average annual minimum temperature also increased for Kharif-I season but decreased for Kharif-II and Rabi season. Study also found that for all cropping season average relative humidity was increased. Annual average rainfall exhibited decreasing trend for Kharif-I and Rabi season but increased for Kharif-II season in (1990-2019) time period. The Aus, T. Aman, Boro and Mung bean was dominant cropping pattern in Kharif-I, Kharif- II and Rabi season in Bhola district. Overall, Aus rice production in Kharif-I season increased but in 2009, 2013 production was decreased because of cyclone Aila (2009) and Cyclone Mahasen (2013). T. Aman production hampered due to Cyclone Sidr (2007) and flood (2014) in Kharif-II season. In Rabi season Boro rice production lessen because of low rainfall and salinity intrusion. Overall, Mung bean production increase but in 2008 and 2009 production become hampered due to late cultivation because of Cyclone Sidr (2007). Fish production rate increase in Bhola specially Hilsha fish because of non-climatic factor like raid in non-fishing time, banned current net but fish production in pond become diminished due to infrequent natural disaster. Practicing of salt and flood tolerant varieties, floating bed vegetable cultivation, and mixed cropping system (mainly for Rabi season), enhanced expedition activities against catching mother Ilish in prohibition period, dredging in the heart of the river which can eventually reduce vulnerabilities and increase crop and fish production in the Bhola region. Int. J. Agril. Res. Innov. Tech. 10(1): 40-55, June 202

Pacific island regional preparedness for El Niño

The El Niño Southern Oscillation (ENSO) cycle is often blamed for disasters in Pacific island communities. From a disaster risk reduction (DRR) perspective, the challenges with the El Niño part of the ENSO cycle, in particular, are more related to inadequate vulnerability reduction within development than to ENSO-induced hazard influences. This paper analyses this situation, filling in a conceptual and geographic gap in El Niño-related research, by reviewing El Niño-related preparedness (the conceptual gap) for Pacific islands (the geographic gap). Through exploring El Niño impacts on Pacific island communities alongside their vulnerabilities, resiliences, and preparedness with respect to El Niño, El Niño is seen as a constructed discourse rather than as a damaging phenomenon, leading to suggestions for El Niño preparedness as DRR as part of development. Yet the attention which El Niño garners might bring resources to the Pacific region and its development needs, albeit in the short term while El Niño lasts. Conversely, the attention given to El Niño could shift blame from underlying causes of vulnerability to a hazard-centric viewpoint. Instead of focusing on one hazard-influencing phenomenon, opportunities should be created for the Pacific region to tackle wider DRR and development concerns

A survey of medicinal plants used by kavirajes of chalna area, Khulna district, Bangladesh

Kavirajes or traditional medicinal practitioners form the primary healthcare providers of the predominantly rural population of Bangladesh. Kavirajes use a variety of medicinal plants for treatment of different ailments. The formulations prepared from medicinal plants vary considerably between Kavirajes of different regions of the country. The objective of this study was to conduct an ethnomedicinal survey amongst the Kavirajes of Chalna area, Khulna district, Bangladesh. That area is known to contain a diversity of medicinal plants. Information on 50 plant species was obtained. These medicinal plants belonged to 49 genera and 33 families. Twenty five plants were used to treat skin diseases and twenty three plants for treatment of intestinal tract disorders, which included constipation, indigestion, stomachache, diarrhea, and dysentery. Fourteen plants were also used by the Kavirajes to treat cancer or tumor. Nine plants were used as insecticide, eight for rheumatoid arthritis, and seven for wounds. Five plants were used to treat jaundice. Five plants were also utilized to treat animal and snake bites, which included tiger bites. Six plants were used to treat diabetes, and two each for the treatment of leprosy, and sexually transmitted diseases like gonorrhea. Five plants were used to treat impotency, while one plant was used as an abortifacient. Three plants wereused to treat helminthiasis, which we found to be quite common amongst the population, while four plants were used to treat heart disorders. Taken together, these plant species offer considerable potential for discovery of novel compounds of pharmacological interest.Key words: Traditional medicine, Chalna, Khulna district, Bangladesh, medicinal plants

Medicinal formulations of a Kanda tribal healer – a tribe on the verge of disappearance in Bangladesh

The Kanda tribe is one of the lesser known small tribes of Bangladesh with an estimated population of about 1700 people (according to them), and on the verge of extinction as a separate entity. To some extent, they have assimilated with the surrounding mainstream Bengali-speaking population, but they still maintain their cultural practices including traditional medicinal practices, for which they have their own tribal healers. Nothing at all has been documented thus far about their traditional medicinal practices and formulations, which are on the verge of disappearance. The Kanda tribe can be found only in scattered tea gardens of Sreemangal in Sylhet district of Bangladesh; dispersion of the tribe into small separated communities isalso contributing to the fast losing of traditional medicinal practices. The objective of the present study was to conduct an ethnomedicinal survey among the traditional healers of the Kanda tribe (in fact, only one such healer was found after extensive searches). Information was collected from the healer with the help of a semi-structured questionnaire and the guided field-walk method. A total of 24 formulations were obtained from the healer containing 34 plants including two plants, which could not beidentified. Besides medicinal plants, the Kanda healer also used the body hairs of the Asiatic black bear (Ursus thibetanus) and bats (Pteropus giganteus giganteus) in one of his formulation for treatment of fever with shivering. The ailments treated by the Kanda healer were fairly common ailments like cuts and wounds, skin diseases, helminthiasis, fever,  respiratory problems (coughs, asthma), gastrointestinal disorders (stomach pain, constipation, diarrhea), burning sensations during urination, various types of pain (headache, body ache, toothache, ear ache), conjunctivitis, poisonous snake, insect or reptile bites, jaundice, andbone fractures. A number of important drugs in allopathic medicine like quinine, artemisinin, and morphine (to name only a few) have been discovered from observing indigenous medicinal practices. From that view point, the formulations used by the Kanda healer merit scientific studies for their potential in the discovery of cheap and effective new drugs. Scientific validation of the medicinal formulations of the Kanda healer can also be effective for treatment of ailments among this tribe, which does not have or does not want to have any contact with modern medicine

Barriers to green supply chain management: An emerging economy context

© 2019 Elsevier Ltd Green supply chain management is attracting increasing attention as a way to decrease the adverse environmental effects of industries worldwide. However, considering the context of an emerging economy like Bangladesh, green supply chain management is still in its inception and has not been widely embraced in the textile industry, and therefore barriers hindering its adoption in emerging economy context demand a comprehensive investigation. This research reviews the viewpoints and hurdles in adopting green supply chain management practices in the context of the Bangladeshi textile industry. A questionnaire survey of Bangladeshi textile practitioners of operations and supply chain management division, having a sample size of thirty, was undertaken to identify the barriers, and a hierarchical cluster analysis technique was used in the detailed analysis of this data. Opinions were sought from experts on the significance of the resulting clusters, considering the relative importance of the barriers. Fifteen barriers to the adoption of green supply chain management were identified in the review of the literature, with these barriers then analyzed by using the data collected from Bangladeshi textile industry practitioners. The research indicates that the most important barrier is that there is low demand from customers and financial constraint resulting from short term little financial benefit to businesses, with lack of government regulations also a commonly faced barrier in adopting green supply chain initiatives. This study will provide valuables insights to practitioners and relevant policy makers about the barriers prevailing in the emerging economies towards the adoption of green supply chain management practices, which, in turn, can guide to undertake appropriate steps for alleviating those barriers

Antihyperglycemic Activities of Leaves of Three Edible Fruit Plants (Averrhoa carambola, Ficus hispida and Syzygium samarangense) of Bangladesh

Averrhoa carambola L. (Oxalidaceae), Ficus hispida L.f. (Moraceae), and Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae) are three common plants in Bangladesh, the fruits of which are edible. The leaves and fruits of A. carambola and F. hispida are used by folk medicinal practitioners for treatment of diabetes, while the leaves of S. samarangense are used for treatment of cold, itches, and waist pain. Since scientific studies are absent on the antihyperglycemic effects of the leaves of the three plants, it was the objective of the present study to evaluate the antihyperglycemic potential of methanolic extract of leaves of the plants in oral glucose tolerance tests carried out with glucose-loaded mice. The extracts at different doses were administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. Significant oral hypoglycemic activity was found with the extracts of leaves of all three plants tested. The fall in serum glucose levels were dose-dependent for every individual plant, being highest at the highest dose tested of 400 mg extract per kg body weight. At this dose, the extracts of A. carambola, F. hispida, and S. samarangense caused, respectively, 34.1, 22.7, and 59.3% reductions in serum glucose levels when compared to control animals. The standard antihyperglycemic drug, glibenclamide, caused a 57.3% reduction in serum glucose levels versus control. Among the three plants evaluated, the methanolic extract of leaves of S. samarangense proved to be the most potent in demonstrating antihyperglycemic effects. The result validates the folk medicinal uses of A. carambola and F. hispida in the treatment of diabetes, and indicates that the leaves of S. samarangense can also possibly be used for amelioration of diabetes-induced hyperglycemia.Key words: Averrhoa carambola, Ficus hispida, Syzygium samarangense, antihyperglycemi

A potent betulinic acid analogue ascertains an antagonistic mechanism between autophagy and proteasomal degradation pathway in HT-29 cells

Betulinic acid (BA), a member of pentacyclic triterpenes has shown important biological activities like anti-bacterial, anti-malarial, anti-inflammatory and most interestingly anticancer property. To overcome its poor aqueous solubility and low bioavailability, structural modifications of its functional groups are made to generate novel lead(s) having better efficacy and less toxicity than the parent compound. BA analogue, 2c was found most potent inhibitor of colon cancer cell line, HT-29 cells with IC50 value 14.9 μM which is significantly lower than standard drug 5-fluorouracil as well as parent compound, Betulinic acid. We have studied another mode of PCD, autophagy which is one of the important constituent of cellular catabolic system as well as we also studied proteasomal degradation pathway to investigate whole catabolic pathway after exploration of 2c on HT-29 cells. Mechanism of autophagic cell death was studied using fluorescent dye like acridine orange (AO) and monodansylcadaverin (MDC) staining by using fluorescence microscopy. Various autophagic protein expression levels were determined by Western Blotting, qRT-PCR and Immunostaining. Confocal Laser Scanning Microscopy (CLSM) was used to study the colocalization of various autophagic proteins. These were accompanied by formation of autophagic vacuoles as revealed by FACS and transmission electron microscopy (TEM). Proteasomal degradation pathway was studied by proteasome-Glo™ assay systems using luminometer.The formation of autophagic vacuoles in HT-29 cells after 2c treatment was determined by fluorescence staining – confirming the occurrence of autophagy. In addition, 2c was found to alter expression levels of different autophagic proteins like Beclin-1, Atg 5, Atg 7, Atg 5-Atg 12, LC3B and autophagic adapter protein, p62. Furthermore we found the formation of autophagolysosome by colocalization of LAMP-1 with LC3B, LC3B with Lysosome, p62 with lysosome. Finally, as proteasomal degradation pathway downregulated after 2c treatment colocalization of ubiquitin with lysosome and LC3B with p62 was studied to confirm that protein degradation in autophagy induced HT-29 cells follows autolysosomal pathway. In summary, betulinic acid analogue, 2c was able to induce autophagy in HT-29 cells and as proteasomal degradation pathway downregulated after 2c treatment so protein degradation in autophagy induced HT-29 cell

Potent and selective chemical probe of hypoxic signaling downstream of HIF-α hydroxylation via VHL inhibition

Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling