Identifying new targets in leukemogenesis using computational approaches

AbstractThere is a need to identify novel targets in Acute Lymphoblastic Leukemia (ALL), a hematopoietic cancer affecting children, to improve our understanding of disease biology and that can be used for developing new therapeutics. Hence, the aim of our study was to find new genes as targets using in silico studies; for this we retrieved the top 10% overexpressed genes from Oncomine public domain microarray expression database; 530 overexpressed genes were short-listed from Oncomine database. Then, using prioritization tools such as ENDEAVOUR, DIR and TOPPGene online tools, we found fifty-four genes common to the three prioritization tools which formed our candidate leukemogenic genes for this study. As per the protocol we selected thirty training genes from PubMed. The prioritized and training genes were then used to construct STRING functional association network, which was further analyzed using cytoHubba hub analysis tool to investigate new genes which could form drug targets in leukemia. Analysis of the STRING protein network built from these prioritized and training genes led to identification of two hub genes, SMAD2 and CDK9, which were not implicated in leukemogenesis earlier. Filtering out from several hundred genes in the network we also found MEN1, HDAC1 and LCK genes, which re-emphasized the important role of these genes in leukemogenesis. This is the first report on these five additional signature genes in leukemogenesis. We propose these as new targets for developing novel therapeutics and also as biomarkers in leukemogenesis, which could be important for prognosis and diagnosis

Inferring the Phylogeny of Bovidae Using Mitochondrial DNA Sequences: Resolving Power of Individual Genes Relative to Complete Genomes

Molecular techniques that assess biodiversity through the analysis of a small segment of mitochondrial genome have been getting wide attention for inferring the mammalian diversity. Due to their highly conserved nature, specific mitochondrial genes offer a promising tool for phylogenetic analysis. However, there is no established criteria for selecting the typical mitochondrial DNA (mtDNA) segments to achieve a greater resolving power. We therefore chose the family Bovidae as a model and compared the tree-topologies resulting from the commonly used and phylogenetically-informative genes including 16S rRNA, 12S rRNA, COI, Cyt b and D-loop with respect to complete mitochondrial genome. The tree topologies from the whole mitochondrial genome of 12 species were not identical albeit similar with those resulting from the five individual genes mentioned above. High bootstrap values were observed for mtDNA compared with that of any single gene. The average pair-wise sequence divergence using different genetic modes was found to be: D-loop (0.229) > Cyt b (0.159) > COI or complete mtDNA (0.143) > 12S rRNA (0.094) > 16S rRNA (0.091). The tree resulting from complete mtDNA clearly separated the 12 taxa of Bovidae into 3 major clusters, one cluster each for subfamily Cervinae and Bovinae and the third cluster comprised the distinctive clades of Caprinae and Antilopinae. However, jumping clades of Antilopinae were observed while using the individual genes. This study showed that Bison bison and Bos Taurus have very close phylogenetic relationship compared to Bubalus bubalis (Bovinae), irrespective of the method used. Our findings suggest that complete mtDNA genome provides most reliable understanding of complex phylogenetic relationships while the reliability of individual gene trees should be verified with high bootstrap support

Modes of Action of Different Classes of Herbicides

The mode of action of herbicides is important for understanding the management, classification, organization, and hierarchy of the herbicides. It also provides an insight into herbicide resistance, which continues to be a problem in sustainable agricultural management. The overuse of herbicides, just like other pesticides such as insecticides, has led to increased development of resistance among weeds, causing injury and destruction of useful plants in agriculture, land management, and other related industries. This chapter focuses on the main theme while providing in-depth analysis of the different modes of action of various classes of herbicides. The modes of action of herbicides are as variable as their chemical compositions as they focus on controlling susceptible plants through various biochemical means. Depending upon the specific mode of action at work, it may involve a plant enzyme or a biological system that the herbicide may interrupt, thus injuring or disrupting the regular plant growth and development and causing eventual plant death. Having an in-depth knowledge of the mode of action of herbicides is important in choosing a specific herbicide for a specific crop, understanding the injury symptoms, and devising an appropriate crop-management strategy

A novel algorithm for integrated control model using swarm robots for intruder detection and rescue schedules

Due to the development of computer controlled tools and expansion of integrated computing applications, more and more controller functions are turning to software implementations. A novel controlling algorithm is designed for continuous optimization tasks. However, they are used to thoroughly optimize and apply different areas. The most intelligent swarm algorithms have been designed for continuous optimization problems. However, they have been applied to discreet optimization and applications in different areas. This article gives experimental results on the control of swarm robots with the help of integrated control model (ICM), around its own axis. Such methodology is quite impressive in development of applications for surveillance, path planning, intruder and obstacle detection, model errors in communication to remove uncertainty. The ICM control design performance is based on comprehensive swarm robot model for the identification of actuators from testing data. The same ICM controllers are designed to be compared with the PID controllers in a variety of tests and collected feedback found 12.37%, 8.69% and 12.09% improved on the basis of thrust produced in the propellers for surveillance

Bayesian, Maximum Parsimony and UPGMA Models for Inferring the Phylogenies of Antelopes Using Mitochondrial Markers

This investigation was aimed to compare the inference of antelope phylogenies resulting from the 16S rRNA, cytochrome-b (cyt-b) and d-loop segments of mitochondrial DNA using three different computational models including Bayesian (BA), maximum parsimony (MP) and unweighted pair group method with arithmetic mean (UPGMA). The respective nucleotide sequences of three Oryx species (Oryx leucoryx, Oryx dammah and Oryx gazella) and an out-group (Addax nasomaculatus) were aligned and subjected to BA, MP and UPGMA models for comparing the topologies of respective phylogenetic trees. The 16S rRNA region possessed the highest frequency of conserved sequences (97.65%) followed by cyt-b (94.22%) and d-loop (87.29%). There were few transitions (2.35%) and none transversions in 16S rRNA as compared to cyt-b (5.61% transitions and 0.17% transversions) and d-loop (11.57% transitions and 1.14% transversions) while comparing the four taxa. All the three mitochondrial segments clearly differentiated the genus Addax from Oryx using the BA or UPGMA models. The topologies of all the gamma-corrected Bayesian trees were identical irrespective of the marker type. The UPGMA trees resulting from 16S rRNA and d-loop sequences were also identical (Oryx dammah grouped with Oryx leucoryx) to Bayesian trees except that the UPGMA tree based on cyt-b showed a slightly different phylogeny (Oryx dammah grouped with Oryx gazella) with a low bootstrap support. However, the MP model failed to differentiate the genus Addax from Oryx. These findings demonstrate the efficiency and robustness of BA and UPGMA methods for phylogenetic analysis of antelopes using mitochondrial markers

BIOACTIVITIES AND CHEMOPROFILING COMPARISONS OF CHENOPODIUM AMBROSIOIDES L. AND CHENOPODIUM BOTRYS L. GROWING IN KASHMIR, INDIA

Objectives: The objectives of the study were the gas chromatography-mass spectrometry (GC-MS) identification and comparison of the chemical constituents, evaluation of the antifungal and anticancer activities of two species of genus Chenopodium, for example, Chenopodium ambrosioides (Ca) and Chenopodium botrys (Cb) growing in Kashmir, Himalayan region.Methods: The hydrodistilled essential oil of Ca and Cb was subjected to GC-MS analysis and antifungal activity for minimum inhibitory concentration (MIC) determination against different human pathogenic fungal strains using broth microdilution assay in 96-well microtiter plates as per the protocol of the clinical and laboratory standards institute (2008 M27-A3). The anti-proliferative ability of the essential oils was also evaluated against the two cell lines MCF-7 (human mammary carcinoma cells) and A549 (Human lung adenocarcinoma epithelial cells).Results: A total of 34 compounds identified in Ca with α-terpinene (37.17%), isoascaridole (20.48%), and ascaridole (14.83%) as the key compounds. The key compounds of Cb were shyobunol (18.91%), and hedycaryol (9.51%), germacrene-D-4-ol (8.57%), with 65 identified compounds. Both the species were found to have comparable antifungal activities against human pathogenic fungi with MIC80 values in the range of 0.031 mg/ml– 0.256 mg/ml for Ca and 0.031 mg/ml–0.126 mg/ml in case of Cb. Maximum anti-proliferative activity was observed at 125 μg/ml concentration in A549 cell line, while as the oils inhibited the growth of MCF-7 cell line at a lower concentration of 31.25 μg/ml.Conclusion: The essential oils of Ca and Cb were found to have potent anticancer and antifungal activities and can have potential use as a natural fungicide

AIMS Philanthropy Project: Studying AI, Machine Learning & Data Science Technology for Good

This project investigates philanthropic activities related to Artificial Intelligence, Machine Learning, and Data Science technology (AIMS). Advances in AIMS technology are impacting the field of philanthropy in substantial ways. This report focuses on methods employed in analyzing and visualizing five data sources: Open Philanthropy grants database, Rockefeller Foundation grants database, Chronicle of Philanthropy article database, GuideStar Nonprofit Database, and Google AI for Social Good grant awardees. The goal was to develop an accessible website platform that engaged human-centered UX user experience design techniques to present information about AIMS Philanthropy (https://www.aims-phil.org/). Each dataset was analyzed for a set of general questions that could be answered visually. The visuals aim to provide answers to these two primary questions: (1) How much funding was invested in AIMS? and (2) What focus areas, applications, discovery, or other purposes was AIMS-funded directed toward? Cumulatively, this project identified 325 unique organizations with a total of $2.6 billion in funding for AIMS philanthropy

Search for a Signal on QCD Critical Point in Central Nucleus-Nucleus Collisions

We discuss that the QCD critical point could appear in central collisions in percolation cluster. We suggest using the nuclear transparency effect and the one of the light nuclear production to identify the critical point.Comment: To appear in the proceedings of the 20th International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions (QM2008), Jaipur, India, February 4-10, 200

Acute Gastric Dilatation Resulting in Gastric Emphysema Following Postpartum Hemorrhage

Acute gastric dilatation is a rare entity, with varying aetiologies the majority of which are benign. Delay in diagnosis and treatment could result in sequelae such as gastric emphysema (pneumatosis), emphysematous gastritis, gangrene, and perforation. Gastric emphysema as a result of a benign nongangrenous condition such as gastroparesis, adynamic ileus can be successfully managed conservatively. Here, we present an interesting case of acute gastric dilatation resulting in gastric emphysema following massive postpartum hemorrhage