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1.
Biopolymers ; : e23383, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32604473

RESUMO

Amyloids are a group of proteins that are capable of forming aggregated amyloid fibrils, which is responsible for many neurodegenerative diseases including Alzheimer's disease (AD). In our previous study, synthesis and characterization of star-shaped poly(D,L-lactide)-b-gelatin (ss-pLG) have been reported. In the present work, we have extended our work to study ss-pLG against protein aggregation. To the best of our knowledge, this is the first report on the inhibition of amyloid fibrillation by protein grafted poly(D,L-lactide). Bovine serum albumin (BSA) was chosen as the model protein, which readily forms fibril under high temperature. We found that ss-pLG efficiently suppressed the fibril formation of BSA compared with gelatin (Gel), which was supported by Thioflavin T assay, circular dichroism (CD) spectroscopy and atomic force microscopy (AFM). In addition, ss-pLG significantly curtailed amyloid-induced hemolysis. We also found that incubation of ss-pLG with neuroblastoma cells (MC65) protected the cells from fibril-induced toxicity. The rescuing efficiency of ss-pLG was better than Gel, which could be attributed to the reduced lamella thickness in branched ss-pLG. These results suggest the significance of gelatin grafting, which probably allows gelatin to interact with the key residues of the amyloidogenic core of BSA effectively.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32614743

RESUMO

BACKGROUND: Metal nanoparticles (NPs) have been widely used for various applications in biomedical sciences including in drug delivery, and as therapeutic agents, but limited owing to their toxicity towards the healthy tissue. This warrants an alternative method, which can achieve the desired activity with much reduced or no toxicity. Being a biological product, Withania somnifera (W. somnifera) is an environment friendly, besides being less toxic as compared to metal-based NPs. However, the exact mechanism of action of W. somnifera for its antibacterial activities have not been studied so far. OBJECTIVE: To develop "silver nanoparticles with root extract of W. somnifera (AgNPs-REWS)" for antimicrobial and anticancer activities. Further, the analysis of their mechanism of action will be studied. METHOD: Using in-silico approach, the molecular docking study has been performed to evaluate the possible antibacterial mechanism of W. somnifera phytochemicals such as Anaferine, Somniferine, Stigmasterol, Withaferin A, Withanolide- A, G, M, and Withanone by inhibition of penicillin binding protein 4 (PBP4). Next, we utilized bottom-up approach for the green synthesis of AgNPs-REWS, performed an indetail phytochemical analysis, confirmed the AgNPs-REWS by SEM, UV-visible spectroscopy, XRD, FT-IR, and HPLC. Eventually, we examined their antibacterial activity. RESULTS: The result of molecular docking, suggest that WS phytochemical (Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone) possess the higher binding affinity toward the active site of PBP4 as compare to Ampicillin (-6.39 kcal/mol) reference molecule. These phytochemicals predicted as potent inhibitor of PBP4. Next, as a proof-of -concept, AgNPs-REWS showed significant antibacterial effect as compared to crude, and control; against Xanthomonas and Ralstonia species. CONCLUSION: The in-silico and molecular docking analysis showed that active constituents of W. somnifera such as Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone possesses inhibition potential for PBP4 and responsible for the antibacterial property of W. somnifera extract. This study also establishes that AgNPs via the green synthesis with REWS showed enhanced antibacterial activity towards pathogenic bacteria.

3.
BMC Pulm Med ; 20(1): 179, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576172

RESUMO

BACKGROUND: A surfactant protein-A-derived peptide, which we call SPA4 peptide (amino acids: GDFRYSDGTPVNYTNWYRGE), alleviates lung infection and inflammation. This study investigated the effects of intratracheally administered SPA4 peptide on systemic, lung, and health parameters in an outbred mouse strain, and in an intratracheal lipopolysaccharide (LPS) challenge model. METHODS: The outbred CD-1 mice were intratracheally administered with incremental doses of SPA4 peptide (0.625-10 µg/g body weight) once every 24 h, for 3 days. Mice left untreated and those treated with vehicle were included as controls. Mice were euthanized after 24 h of last administration of SPA4 peptide. In order to assess the biological activity of SPA4 peptide, C57BL6 mice were intratracheally challenged with 5 µg LPS/g body weight and treated with 50 µg SPA4 peptide via intratracheal route 1 h post LPS-challenge. Mice were euthanized after 4 h of LPS challenge. Signs of sickness and body weights were regularly monitored. At the time of necropsy, blood and major organs were harvested. Blood gas and electrolytes, serum biochemical profiles and SPA4 peptide-specific immunoglobulin G (IgG) antibody levels, and common lung injury markers (levels of total protein, albumin, and lactate, lactate dehydrogenase activity, and lung wet/dry weight ratios) were determined. Lung, liver, spleen, kidney, heart, and intestine were examined histologically. Differences in measured parameters were analyzed among study groups by analysis of variance test. RESULTS: The results demonstrated no signs of sickness or changes in body weight over 3 days of treatment with various doses of SPA4 peptide. It did not induce any major toxicity or IgG antibody response to SPA4 peptide. The SPA4 peptide treatment also did not affect blood gas, electrolytes, or serum biochemistry. There was no evidence of injury to the tissues and organs. However, the SPA4 peptide suppressed the LPS-induced lung inflammation. CONCLUSIONS: These findings provide an initial toxicity profile of SPA4 peptide. Intratracheal administration of escalating doses of SPA4 peptide does not induce any significant toxicity at tissue and organ levels. However, treatment with a dose of 50 µg SPA4 peptide, comparable to 2.5 µg/g body weight, alleviates LPS-induced lung inflammation.

4.
Indian J Ophthalmol ; 68(7): 1381-1384, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32587169

RESUMO

Purpose: COVID-19 related pan- India lockdown brought teleophthalmology to the forefront. The study ventures to understand the relevance of this modality in a government setup. The objective is to understand the feasibility, clinical profile and addressability of patients using teleconsultation in ophthalmology at a tertiary care government medical university during the COVID-19 Lockdown in India. Methods: An online survey targeting faculty members and resident doctors in a tertiary eye center in a government medical university in north India was conducted. Various aspects of teleconsultation were analyzed including the number and preferential mode of consultations, commonest complaints and diagnoses made. Frequency and factors mandating physical examination of patients was also analyzed. Results: The questionnaire was sent to 40 ophthalmologists of whom 38 responded. A total of 4880 teleconsultations were given. The commonest mode of communication was by WhatsApp messages (65.6%) and E-mail was the least preferred medium. More than 80% consultations were from previously seen patients. Red eye was the commonest presenting complaint (22.8%), followed by watering (18.7%) and foreign body sensation (14.5%). Computer vision syndrome was the commonest diagnosis (25.9%) followed by conjunctivitis (17.7%) and refractive error (17.7%). About 40% required physical examination, mostly due to uncertain diagnosis (22%) or inadequate response to prescribed treatment (19%). Conclusion: Teleconsultation was feasible in a government medical university for providing ophthalmic services during lockdown. WhatsApp was the preferred communication modality, computer vision syndrome was the most frequent tentative diagnosis and approximately 60% did not require in-person physical examination.

5.
Soft Matter ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32572423

RESUMO

We propose a novel and efficient mixing technique in a soft narrow-fluidic channel under the influence of electrical forcing. We show that a grafted polyelectrolyte layer (PEL) added as a patch to the channel wall modulates the electrical double layer (EDL) so that an applied electric field initiates a local electroosmotic flow (EOF) at the patched section. This EOF develops in the opposite direction to the primary pressure-driven flow. This localized EOF leads to the formation of Lamb vortices at the patched sections through the phenomenon of momentum exchange with the primary stream and promotes the mixing therein. Our study, consistent with the stream-function/vorticity approach, primarily focuses on the numerical analysis of the mixing phenomena. Through a quantitative description, we reveal the effect of different patterns on the underlying mixing phenomena in the convective mixing regime. We also discuss the impact of key parameters on the mixing efficiency, the onset of the recirculation zone, variation in the mixing length, and the shear-driven aggregation kinetics in soft matter systems. Finally, considering the practicability of the present problem, we unveil the values of several design parameters for which the mixing efficiency in the channel reaches the maximum.

7.
Nat Commun ; 11(1): 2856, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503977

RESUMO

Type I interferon (IFN-I) and T helper 17 (TH17) drive pathology in neuromyelitis optica spectrum disorder (NMOSD) and in TH17-induced experimental autoimmune encephalomyelitis (TH17-EAE). This is paradoxical because the prevalent theory is that IFN-I inhibits TH17 function. Here we report that a cascade involving IFN-I, IL-6 and B cells promotes TH17-mediated neuro-autoimmunity. In NMOSD, elevated IFN-I signatures, IL-6 and IL-17 are associated with severe disability. Furthermore, IL-6 and IL-17 levels are lower in patients on anti-CD20 therapy. In mice, IFN-I elevates IL-6 and exacerbates TH17-EAE. Strikingly, IL-6 blockade attenuates disease only in mice treated with IFN-I. By contrast, B-cell-deficiency attenuates TH17-EAE in the presence or absence of IFN-I treatment. Finally, IFN-I stimulates B cells to produce IL-6 to drive pathogenic TH17 differentiation in vitro. Our data thus provide an explanation for the paradox surrounding IFN-I and TH17 in neuro-autoimmunity, and may have utility in predicting therapeutic response in NMOSD.

8.
Biomolecules ; 10(5)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32375303

RESUMO

Recent advances in woundcare is targeted towards developing active-dressings, where multiple components are combined to provide a suitable environment for rapid healing. The aim of the present research is to study the preparation of biomimic composite wound dressings by the grafting of hydrogel on silk fibroin fabric. The swelling ability of hydrogel grafted silk fibroin fabric was optimized by changing the initiator concentration. In order to impart antimicrobial properties, these dressing are further coated sono-chemically with zinc oxide nanoparticles. The water vapor transmission rate of the prepared samples was measured. The conformation of silk fibroin proteins after grafting with hydrogel was also confirmed using Fourier Transform Infrared Spectroscopy (FTIR). The morphology of the zinc oxide-coated silk fibroin fabric and hydrogel-coated silk fibroin was studied using Scanning Electron Microscope (SEM). The antimicrobial activity of the zinc oxide-coated samples was studied against E coli. The cytocompatibility of the prepared dressing materials were evaluated using L929 fibroblast cells. MTT assay and phase contrast microscopic studies showed that the adherence, growth, and proliferation of the L929 fibroblast cells that were seeded on zinc oxide nanoparticles on the functionalized hydrogel-coated silk fibroin dressing was significantly higher than that of pure silk fibroin due to the highly porous, bio-mimic structure that allowed ease of passage of nutrients, growth factors, metabolites, and the exchange of gases which is beneficial for successful regeneration of damaged tissues. The expression of TNF-α and IL-2 were not significantly higher than that of control. The proposed composite dressing would be a promising material for wound dressing and regenerative medicine but in order to prove the efficacy of these materials, more in vivo experiments and clinical tests are required to be conducted in future.

9.
Prep Biochem Biotechnol ; : 1-9, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32393146

RESUMO

Biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a promising alternative to the conventional chemical synthesis approach. In this study, cost-effective synthesis of AgNPs was attempted using leaves extract of Litchi chinensis. Bio-reduction reaction for the synthesis of NPs was checked by confirming the presence of AgNPs in solution by UV-vis spectrophotometry and with further characterization by fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). Surface plasmon resonance (SPR) band showed absorption peak at 422 nm indicating the formation of AgNPs, and FTIR spectra confirmed the presence of biological molecules involved in AgNPs synthesis. TEM analysis revealed the spherical shape of AgNPs with particle size distribution in a range of 5-15 nm. Further, the biosynthesized AgNPs showed significant bactericidal and sporicidal activity against model spore former Bacillus subtilis. AgNPs at concentrations ranging from 25 to 100 µg/mL showed bactericidal activity with inhibition zone ranging from 4-19 mm and sporicidal activity at 100-200 µg/mL in a range of 4.46-61.6% with an exposure time of 2-8 h. These findings exhibit distinctive potential of biogenic AgNPs for their efficient use in developing novel bactericidal and sporicidal agent against spore forming bacilli.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32413202

RESUMO

Phosphorus-modified all-silica zeolites exhibit activity and selectivity in certain Brønsted acid catalyzed reactions for biomass conversion. In an effort to achieve similar performance with catalysts having well-defined sites, we report the incorporation of Brønsted acidity to metal-organic frameworks with the UiO-66 topology, achieved by attaching phosphonic acid to the 1,4-benzenedicarboxylate ligand and using it to form UiO-66-PO3 H2 by post-synthesis modification. Characterization reveals that UiO-66-PO3 H2 retains stability similar to UiO-66, and exhibits weak Brønsted acidity, as demonstrated by titrations, alcohol dehydration, and dehydra-decyclization of 2-methyltetrahydrofuran (2-MTHF). For the later reaction, the reported catalyst exhibits site-time yields and selectivity approaching that of phosphoric acid on all-silica zeolites. Using solid-state NMR and deprotonation energy calculations, the chemical environments of P and the corresponding acidities are determined.

11.
Indian J Public Health ; 64(1): 22-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189678

RESUMO

Background: Cold chain equipments (CCEs) at health facilities (HFs) are an essential part of the immunization supply chain (ISC). The CCEs in government HFs of Delhi were never assessed using the World Health Organization-United Nations Children's Fund (WHO-UNICEF) Effective Vaccine Management (EVM) tool except that of state vaccine store during National EVM assessment 2013. Objectives: The objective of the study was to assess the CCEs and their management in government HFs using the WHO-UNICEF EVM tool in a district of Delhi. Methods: The assessment was done during December 2017-March 2018 in one randomly selected district of Delhi. Sample size and site selection were done using the WHO EVM site selection tool. A total of 29 HFs were assessed along with District Vaccine Store. Questions on CCEs in EVM tool 1.0.9 were used for data collection. Results: Out of 56 electrical CCEs, 8.9% were nonfunctional, 48.2% were noncompliant with WHO standards, 5.4% were not chlorofluorocarbon free, 4.7% did not have temperature monitoring device, and 18.8% did not have stabilizer. Eighty-six percent of passive containers were compliant with the WHO standards. The storage capacity of electrical vaccine storage equipment was insufficient in 3.4%, passive container capacity in 65.5%, and ice packs preparation and storage capacity in 24.1% of HFs. There was no planned preventive maintenance of CCEs and no standard operating procedures for emergency event management. Conclusion: There was a shortage of vaccine storage, ice packs preparation and storage, and passive container capacity. Many CCEs used in ISC of assessed sites were noncompliant to the WHO standards. There was no PPM of CCEs and no guidelines for emergency event management.

13.
Mol Neurobiol ; 57(5): 2479-2493, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157575

RESUMO

CRIPT, the cysteine-rich PDZ-binding protein, binds to the third PDZ domain of PSD-95 (postsynaptic density protein 95) family proteins and directly binds microtubules, linking PSD-95 family proteins to the neuronal cytoskeleton. Here, we show that overexpression of a full-length CRIPT leads to a modest decrease, and knockdown of CRIPT leads to an increase in dendritic branching in cultured rat hippocampal neurons. Overexpression of truncated CRIPT lacking the PDZ domain-binding motif, which does not bind to PSD-95, significantly decreases dendritic arborization. Conversely, overexpression of a full-length CRIPT significantly increases the number of immature and mature dendritic spines, and this effect is not observed when CRIPT∆PDZ is overexpressed. Competitive inhibition of CRIPT binding to the third PDZ domain of PSD-95 with PDZ3-binding peptides resulted in differential effects on dendritic arborization based on the origin of respective peptide sequence. These results highlight multifunctional roles of CRIPT during development and underscore the significance of the interaction between CRIPT and the third PDZ domain of PSD-95.

14.
Biochim Biophys Acta Mol Basis Dis ; 1866(7): 165769, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184133

RESUMO

Brain is well known for its disproportionate oxygen consumption and high energy-budget for optimal functioning. The decrease in oxygen supply to brain, thus, necessitates rapid activation of adaptive pathways - the absence of which manifest into vivid pathological conditions. Amongst these, oxygen sensing in glio-vascular milieu and H2S-dependent compensatory increase in cerebral blood flow (CBF) is a major adaptive response. We had recently demonstrated that the levels of H2S were significantly decreased during chronic hypobaric hypoxia (HH)-induced neuro-pathological effects. The mechanistic basis of this phenomenon, however, remained to be deciphered. We, here, describe experimental evidence for marked limitation of cysteine during HH - both in animal model as well as human volunteers ascending to high altitude. We show that the preservation of brain cysteine level, employing cysteine pro-drug (N-acetyl-L-cysteine, NAC), markedly curtailed effects of HH - not only on endogenous H2S levels but also, impairment of spatial reference memory in our animal model. We, further, present multiple lines of experimental evidence that the limitation of cysteine was causally governed by physiological propensity of brain to utilize cysteine, in cystathionine beta synthase (CBS)-dependent manner, past its endogenous replenishment potential. Notably, decrease in the levels of brain cysteine manifested despite positive effect (up-regulation) of HH on endogenous cysteine maintenance pathways and thus, qualifying cysteine as a conditionally essential nutrient (CEN) during HH. In brief, our data supports an adaptive, physiological role of CBS-mediated cysteine-utilization pathway - activated to increase endogenous levels of H2S - for optimal responses of brain to hypobaric hypoxia.

15.
J Immunol ; 204(8): 2076-2087, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169842

RESUMO

Dysregulated Th17 cell differentiation is associated with autoimmune diseases such as multiple sclerosis, which has no curative treatment. Understanding the molecular mechanisms of regulating Th17 cell differentiation will help find a novel therapeutic target for treating Th17 cell-mediated diseases. In this study, we investigated the cell-intrinsic processes by which RNA-binding protein HuR orchestrates Th17 cell fate decisions by posttranscriptionally regulating transcription factors Irf4 and Runx1 and receptor Il12rb1 expression, in turn promoting Th17 cell and Th1-like Th17 cell differentiation in C57BL/6J mice. Knockout of HuR altered the transcriptome of Th17 cells characterized by reducing the levels of RORγt, IRF4, RUNX1, and T-bet, thereby reducing the number of pathogenic IL-17+IFN-γ+CD4+ T cells in the spleen during experimental autoimmune encephalomyelitis. In keeping with the fact that HuR increased the abundance of adhesion molecule VLA-4 on Th17 cells, knockout of HuR impaired splenic Th17 cell migration to the CNS and abolished the disease. Accordingly, targeting HuR by its inhibitor DHTS inhibited splenic Th17 cell differentiation and reduced experimental autoimmune encephalomyelitis severity. In sum, we uncovered the molecular mechanism of HuR regulating Th17 cell functions, underscoring the therapeutic value of HuR for treatment of autoimmune neuroinflammation.

16.
Angew Chem Int Ed Engl ; 59(24): 9579-9585, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32115827

RESUMO

Commonly used methods to assess crystallinity, micro-/mesoporosity, Brønsted acid site density and distribution (in micro- vs. mesopores), and catalytic activity suggest nearly invariant structure and function for aluminosilicate zeolite MFI two-dimensional nanosheets before and after superheated steam treatment. Yet, pronounced reaction rate decrease for benzyl alcohol alkylation with mesitylene, a reaction that cannot take place in the zeolite micropores, is observed. Transmission electron microscopy images reveal pronounced changes in nanosheet thickness, aspect ratio and roughness indicating that nanosheet coarsening and the associated changes in the external (mesoporous) surface structure are responsible for the changes in the external surface catalytic activity. Superheated steam treatment of hierarchical zeolites can be used to alter nanosheet morphology and regulate external surface catalytic activity while preserving micro- and mesoporosity, and micropore reaction rates.

17.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-32020909

RESUMO

Rice tungro is a serious viral disease of rice resulting from infection by two viruses, Rice tungro bacilliform virus and Rice tungro spherical virus. To gain molecular insights into the global gene expression changes in rice during tungro, a comparative whole genome transcriptome study was performed on healthy and tungroaffected rice plants using Illumina Hiseq 2500. About 10 GB of sequenced data comprising about 50 million paired end reads per sample were then aligned on to the rice genome. Gene expression analysis revealed around 959 transcripts, related to various cellular pathways concerning stress response and hormonal homeostasis to be differentially expressed. The data was validated through qRT-PCR. Gene ontology and pathway analyses revealed enrichment of transcripts and processes similar to the differentially expressed genes categories. In short, the present study is a comprehensive coverage of the differential gene expression landscape and provides molecular insights into the infection dynamics of the rice-tungro virus system.

18.
Brain Inj ; 34(5): 685-693, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32064956

RESUMO

Primary Objective: Limited available therapeutics for ischemic stroke necessitate dire need of designing novel strategies for combating ischemic pathophysiological cascade among which neuroprotective strategies emerge as positive approaches. The neuropeptide prolactin is a pleiotropic hormone that affects various physiological conditions and reportedly combats neurotoxicity, neuronal stress and provides neuroprotection to hippocampal neurons in vitro.Research Design: The study explores the ability of prolactin in conferring neuroprotection in global cerebral ischemia in vivo and attempts to optimize the dose of prolactin which will be effective for the same.Methods and Procedure: Global cerebral ischemia was induced in male rats by bilateral common carotid occlusion (BCCAO) and different physiological and biochemical parameters were evaluated. Also, cerebral infarction and percentage of brain edema were measured.Results: The results revealed that prolactin significantly reduces cerebral infarct, brain water content and restores the physiological conditions like blood pressure, heart rate and cerebral blood flow. Also, prolactin markedly reduces the increased levels of the neurotransmitters (É£-aminobutyric acid and glutamate), cerebral calcium and nitrate in different brain compartments of ischemic rats.Conclusion: Prolactin is able to ameliorate ischemia-reperfusion injury in rat brain and might be a potent candidate for further neuro-therapeutics development.

19.
Blood ; 135(18): 1560-1573, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32040545

RESUMO

Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cell growth, whereas expression of the closely related CDK4 protein is dispensable. Moreover, CDK6 silencing is more effective than treatment with the dual CDK4/6 inhibitor palbociclib in suppressing Ph+ ALL in mice, suggesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL. Accordingly, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression. No such effects were observed in CD34+ normal hematopoietic progenitors, although CDK6 was efficiently degraded. Treatment with the CDK6-degrading PROTAC YX-2-107 markedly suppressed leukemia burden in mice injected with de novo or tyrosine kinase inhibitor-resistant primary Ph+ ALL cells, and this effect was comparable or superior to that of the CDK4/6 enzymatic inhibitor palbociclib. These studies provide "proof of principle" that targeting CDK6 with PROTACs that inhibit its enzymatic activity and promote its degradation represents an effective strategy to exploit the "CDK6 dependence" of Ph+ ALL and, perhaps, of other hematologic malignancies. Moreover, they suggest that treatment of Ph+ ALL with CDK6-selective PROTACs would spare a high proportion of normal hematopoietic progenitors, preventing the neutropenia induced by treatment with dual CDK4/6 inhibitors.

20.
BMC Bioinformatics ; 21(1): 56, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054449

RESUMO

BACKGROUND: Quality Control in any high-throughput sequencing technology is a critical step, which if overlooked can compromise an experiment and the resulting conclusions. A number of methods exist to identify biases during sequencing or alignment, yet not many tools exist to interpret biases due to outliers. RESULTS: Hence, we developed iSeqQC, an expression-based QC tool that detects outliers either produced due to variable laboratory conditions or due to dissimilarity within a phenotypic group. iSeqQC implements various statistical approaches including unsupervised clustering, agglomerative hierarchical clustering and correlation coefficients to provide insight into outliers. It can be utilized through command-line (Github: https://github.com/gkumar09/iSeqQC) or web-interface (http://cancerwebpa.jefferson.edu/iSeqQC). A local shiny installation can also be obtained from github (https://github.com/gkumar09/iSeqQC). CONCLUSION: iSeqQC is a fast, light-weight, expression-based QC tool that detects outliers by implementing various statistical approaches.


Assuntos
Perfilação da Expressão Gênica/normas , Sequenciamento de Nucleotídeos em Larga Escala/normas , Análise de Sequência de RNA/normas , Software , Análise por Conglomerados , Humanos , Controle de Qualidade
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