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151.
Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway
Jian Carrot-Zhang Xiaotong Yao Siddhartha Devarakonda Aditya Deshpande Jeffrey S. Damrauer Tiago Chedraoui Silva Christopher K. Wong Hyo Young Choi Ina Felau A. Gordon Robertson Mauro A.A. Castro Lisui Bao Esther Rheinbay Eric Minwei Liu Tuan Trieu David Haan Christina Yau Toshinori Hinoue Marcin Imielinski 《Cell reports》2021,34(8):108784
152.
Sehgal AK Das S Noto K Saier MH Elkan C 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2011,8(3):851-857
With well over 1,000 specialized biological databases in use today, the task of automatically identifying novel, relevant data for such databases is increasingly important. In this paper, we describe practical machine learning approaches for identifying MEDLINE documents and Swiss-Prot/TrEMBL protein records, for incorporation into a specialized biological database of transport proteins named TCDB. We show that both learning approaches outperform rules created by hand by a human expert. As one of the first case studies involving two different approaches to updating a deployed database, both the methods compared and the results will be of interest to curators of many specialized databases. 相似文献
153.
Zong Z Desai SD Kaushal AM Barich DH Huang HS Munson EJ Suryanarayanan R Kirsch LE 《AAPS PharmSciTech》2011,12(3):924-931
Gabapentin is known to undergo intramolecular cyclization to form a lactam (gaba-l) with concomitant loss of water. Gabapentin was milled in a planetary mill for 15–60 min. Unmilled and milled gabapentin
were stored at 50°C with relative humidity ranged between 5% and 90%. The unmilled and milled samples were assayed for gabapentin
and gaba-l by reversed phase-high-performance liquid chromatography and also subjected to powder X-ray diffraction, solid-state nuclear
magnetic resonance and surface area analyses. The rates of lactamization in the milled gabapentin samples correlated to increased
surface area, milling duration, and in-process lactam levels. This effect of milling could not be explained solely by the
increase in surface area with increased milling time but was more likely due to increased regions of crystal disorder caused
by the mechanical and thermal milling stresses. The lactamization rate of milled gabapentin samples was greatest in the presence
of the lowest humidity conditions and dramatically decreased with increasing humidity. In particular, milled gabapentin appeared
to be much more stable at humidity levels greater than 31% RH. This finding could not be attributed to the possibility of
lactam hydrolysis at high humidity but rather to a competitive annealing process wherein milling-induced crystal defects were
lost upon exposure to atmospheric moisture thereby stabilizing the milling-damaged drug substance. 相似文献
154.
155.
Gursharan Singh Aditya Bhalla Paramjit Kaur Neena Capalash Prince Sharma 《Reviews in Environmental Science and Biotechnology》2011,10(4):309-326
Laccases (benzenediol: oxygen oxidoreductase, EC 1.10.3.2) are multi-copper-containing enzymes capable of catalyzing the oxidation
of a wide range of phenolic and non phenolic aromatic compounds. The available data indicates that laccases from prokaryotes
are promising biological tools for green chemistry based applications, especially in decolorization of industrial textile
dye effluents which constitute a major threat to soil and ground water reservoirs worldwide. Another appropriate application
of prokaryotic laccases is bio-bleaching of different kind of pulps where there is indiscriminate use of hazardous chlorine
based chemicals for brightness of the paper. In recent years, researchers have shown interest in the identification and characterization
of laccases from prokaryotic sources. This catalyst is not commonly reported from this kingdom, although prokaryotes have
immense environmental adaptability and biochemical versatility. Moreover, true laccases or laccase-like enzymes exist in many
gram-negative, gram-positive bacteria and actinomycetes. Corresponding genes have been identified and functionally expressed
in genetically developed hosts. This review summarizes the research efforts to characterize laccases and their properties
from different prokaryotic sources, including bacteria and actinomycetes. 相似文献
156.
Gupta A Nadkarni G Yang WT Chandrasekhar A Gupte N Bisson GP Hosseinipour M Gummadi N 《PloS one》2011,6(12):e28691
Background
We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known.Methods and Findings
Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA.Conclusions
Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed. 相似文献157.
Antibody-drug conjugates (ADCs), produced through the chemical linkage of a potent small molecule cytotoxin (drug) to a monoclonal antibody, have more complex and heterogeneous structures than the corresponding antibodies. This review describes the analytical methods that have been used in their physicochemical characterization. The selection of the most appropriate methods for a specific ADC is heavily dependent on the properties of the linker, the drug and the choice of attachment sites (lysines, inter-chain cysteines, Fc glycans). Improvements in analytical techniques such as protein mass spectrometry and capillary electrophoresis have significantly increased the quality of information that can be obtained for use in product and process characterization and for routine lot release and stability testing.Key words: antibody drug conjugates, physicochemical characterization, analytical methods, auristatins, maytansines, biophysical characterization, drug distribution, drug loading, drug to antibody ratio 相似文献
158.
Background
The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense.Methodology
Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1–50 ng/mL) for 12–72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays.Results
The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue.Conclusions/Significance
Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications. 相似文献159.
Aditya Arun Kumar Debolina Hati Thana’a Mohajer Thaker Layeque Miah Phil Cunningham Carmen Domene Tam T.T. Bui Alex F. Drake Lindsay C. McDermott 《FEBS letters》2013
Zinc-α2-glycoprotein (ZAG) is an adipokine with an MHC class I-like protein fold. Even though zinc causes ZAG to precipitate from plasma during protein purification, no zinc binding has been identified to date. Using mass spectrometry, we demonstrated that ZAG contains one strongly bound zinc ion, predicted to lie close to the α1 and α2 helical groove. UV, CD and fluorescence spectroscopies detected weak zinc binding to holo-ZAG, which can bind up to 15 zinc ions. Zinc binding to 11-(dansylamino) undecanoic acid was enhanced by holo-ZAG. Zinc binding may be important for ZAG binding to fatty acids and the β-adrenergic receptor. 相似文献
160.
Withania somnifera (L.) is one of the most valuable medicinal plants used in Ayurvedic and other indigenous medicines. Pharmaceutical activities of this herb are associated with presence of secondary metabolites known as withanolides, a class of phytosteroids synthesized via mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate pathways. Though the plant has been well characterized in terms of phytochemical profiles as well as pharmaceutical activities, not much is known about the genes responsible for biosynthesis of these compounds. In this study, we have characterized two genes encoding 1-deoxy-d-xylulose-5-phosphate synthase (DXS; EC 2.2.1.7) and 1-deoxy-d-xylulose-5-phosphate reductase (DXR; EC 1.1.1.267) enzymes involved in the biosynthesis of isoprenoids. The full-length cDNAs of W. somnifera DXS (WsDXS) and DXR (WsDXR) of 2,154 and 1,428 bps encode polypeptides of 717 and 475 amino acids residues, respectively. The expression analysis suggests that WsDXS and WsDXR are differentially expressed in different tissues (with maximal expression in flower and young leaf), chemotypes of Withania, and in response to salicylic acid, methyl jasmonate, as well as in mechanical injury. Analysis of genomic organization of WsDXS shows close similarity with tomato DXS in terms of exon–intron arrangements. This is the first report on characterization of isoprenoid biosynthesis pathway genes from Withania. 相似文献