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1.
Drug Test Anal ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646611

RESUMO

The illicit drug overdose crisis in North America continues to devastate communities with fentanyl detected in the majority of illicit drug overdose deaths. The COVID-19 pandemic has heightened concerns of even greater unpredictability in the drug supplies and unprecedented rates of overdoses. Portable drug-checking technologies are increasingly being integrated within overdose prevention strategies. These emerging responses are raising new questions about which technologies to pursue and what service models can respond to the current risks and contexts. In what has been referred to as the epicenter of the overdose crisis in Canada, a multi-technology platform for drug checking is being piloted in community settings using a suite of chemical analytical methods to provide real-time harm reduction. These include infrared absorption, Raman scattering, gas chromatography with mass spectrometry, and antibody-based test strips. In this Perspective, we illustrate some advantages and challenges of using multiple techniques for the analysis of the same sample, and provide an example of a data analysis and visualization platform that can unify the presentation of the results and enable deeper analysis of the results. We also highlight the implementation of a various service models that co-exist in a research setting, with particular emphasis on the way that drug checking technicians and harm reduction workers interact with service users. Finally, we provide a description of the challenges associated with data interpretation and the communication of results to a diverse audience.

2.
Plant Mol Biol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629224

RESUMO

KEY MESSAGE: Overexpression of StCaM2 in tobacco promotes plant growth and confers increased salinity and drought tolerance by enhancing the photosynthetic efficiency, ROS scavenging, and recovery from membrane injury. Calmodulins (CaMs) are important Ca2+ sensors that interact with effector proteins and drive a network of signal transduction pathways involved in regulating the growth and developmental pattern of plants under stress. Herein, using in silico analysis, we identified 17 CaM isoforms (StCaM) in potato. Expression profiling revealed different temporal and spatial expression patterns of these genes, which were modulated under abiotic stress. Among the identified StCaM genes, StCaM2 was found to have the largest number of abiotic stress responsive promoter elements. In addition, StCaM2 was upregulated in response to some of the selected abiotic stress in potato tissues. Overexpression of StCaM2 in transgenic tobacco plants enhanced their tolerance to salinity and drought stress. Accumulation of reactive oxygen species was remarkably decreased in transgenic lines compared to that in wild type plants. Chlorophyll a fluorescence analysis suggested better performance of photosystem II in transgenic plants under stress compared to that in wild type plants. The increase in salinity stress tolerance in StCaM2-overexpressing plants was also associated with a favorable K+/Na+ ratio. The enhanced tolerance to abiotic stresses correlated with the increase in the activities of anti-oxidative enzymes in transgenic tobacco plants. Overall, our results suggest that StCaM2 can be a novel candidate for conferring salt and drought tolerance in plants.

3.
Sci Rep ; 11(1): 3572, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574377

RESUMO

Root lesion nematode (RLN; Pratylenchus thornei) causes extensive yield losses in wheat worldwide and thus pose serious threat to global food security. Reliance on fumigants (such as methyl bromide) and nematicides for crop protection has been discouraged due to environmental concerns. Hence, alternative environment friendly control measures like finding and deployment of resistance genes against Pratylenchus thornei are of significant importance. In the present study, genome-wide association study (GWAS) was performed using single-locus and multi-locus methods. In total, 143 wheat genotypes collected from pan-Indian wheat cultivation states were used for nematode screening. Genotypic data consisted of  > 7K SNPs with known genetic positions on the high-density consensus map was used for association analysis. Principal component analysis indicated the existence of sub-populations with no major structuring of populations due to the origin. Altogether, 25 significant marker trait associations were detected with - log10 (p value) > 4.0. Three large linkage disequilibrium blocks and the corresponding haplotypes were found to be associated with significant SNPs. In total, 37 candidate genes with nine genes having a putative role in disease resistance (F-box-like domain superfamily, Leucine-rich repeat, cysteine-containing subtype, Cytochrome P450 superfamily, Zinc finger C2H2-type, RING/FYVE/PHD-type, etc.) were identified. Genomic selection was conducted to investigate how well one could predict the phenotype of the nematode count without performing the screening experiments. Prediction value of r = 0.40 to 0.44 was observed when 56 to 70% of the population was used as a training set. This is the first report where GWAS has been conducted to find resistance against root lesion nematode (P. thornei) in Indian wheat germplasm.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33602080

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which is a cause of the ongoing pandemic, has the potential to infect the nervous system and causing neurological manifestations. However, patients with primarily neurological symptoms are often overlooked and tested later. OBJECTIVE: We aim to summarise all the neurological manifestations which are reported so far to aid in early diagnosis and preventingze all the neurological manifestations that are reported so far to aid in early diagnosis and prevent further complication of the disease. METHODS AND MATERIAL: We did a literature search on the topic using Google search engine through Google Scholar, PubMed, and WHO resources by keywords including Coronavirus, SARS-CoV-2, COVID-19, Clinical features, Stroke, Transverse myelitis, Encephalitis, Encephalopathy, Guillain-Barre syndrome, Hypogeusia, Hyposmia, Anosmia, and Neurological manifestations. DISCUSSION: SARS-CoV-2 can affect the neuronal cells by both direct and indirect mechanisms. This can lead to various neurological manifestations ranging from subtle symptoms of myalgia, headache, dizziness, hypogeusia, hyposmia to dreaded complications like stroke, encephalitis, demyelinating disease like Guillain-Barre syndrome. CONCLUSIONS: Presentation of COVID-19 with neurological features is not uncommon, and these patients should be tested earlier to help in the prevention of transmission, early diagnosis, and management.

5.
Langmuir ; 37(5): 1714-1724, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33513022

RESUMO

We describe an experimental study of soft solids composed of micron-scale lipid bilayer vesicles that adhere to one another through electrostatic attraction to an oppositely charged polymer (PDADMAC). As the polymer concentration was increased, we found a fluid phase, a solid gel phase, and a gel composed of internally reorganized vesicles. Optical microscopy images showed a nearly close-packed structure of adhered vesicles that retained their closed-cell morphology. Shear rheology measurements showed that the gel phase is a solid with a modulus at the Pa scale and with linear response up to 70% strain. We found that the modulus depends on the energy per area of membrane-membrane adhesion but does not depend on the vesicle size. We further found that the gels survived osmotic stress or dilution of the adhering polymer but could be rapidly disrupted in response to the addition of strongly binding silica nanoparticles. These results demonstrate the potential for cell-sized lipid vesicles to form a solid platform that maintains the responsive properties of the membranes. Such materials may find applications as triggerable, protective coatings of delicate surfaces.

6.
Am J Kidney Dis ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33418012

RESUMO

The publisher regrets that this article has been temporarily removed as it was mistakenly published online early. The article will be reinstated with the corrected proof as soon as possible. The full Elsevier Policy on Article Withdrawal can be found at: https://www.elsevier.com/about/our-business/policies/article-withdrawal.

8.
Biochem Biophys Res Commun ; 541: 15-21, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33461063

RESUMO

A scientific approach is presented describing the fabrication of nanoprobe (GloTrack) that can act as cardiac precursor label to segregate cells from cardiac/non cardiac origins and traced by magnetic resonance imaging (MRI). Signal regulatory protein alpha (SIRPA) and kinase domain receptor (KDR) recognizing antibodies, form a layer on super paramagnetic iron oxide nanoparticle - poly-ethylene glycol (SPION-PEG) complex, and bind to protein expressed on the surface of cardiac muscle cells. Physical attributes size, distribution, labelling efficiency, echocardiogram (ECG) changes and bio-distribution by MRI were analysed. The results indicate that GloTrack has an average size of 471 nm, exhibits negative potential and promotes labelling efficiency. The bio-distribution of GloTrack in in vivo experiments was traceable in 7T MRI showing high accumulation of GloTrack in cardiac muscles as compared to the liver and spleen. ECG data revealed that GloTrack segregated cardiac precursors has the potential benefit in treating heart failure, thereby paving way in the development of minimal cell manipulation with targeted cell delivery approaches.

9.
Sci Rep ; 11(1): 2487, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514790

RESUMO

The present study investigates the impact of charge variants on bevacizumab's structure, stability, and biological activity. Five basic and one acidic charge variants were separated using semi-preparative cation exchange chromatography using linear pH gradient elution with purity > 85%. Based on the commercial biosimilar product's composition, two basic variants, one acidic and the main bevacizumab product, were chosen for further investigation. Intact mass analysis and tryptic peptide mapping established the basic variants' identity as those originating from an incomplete clipping of either one or both C-terminal lysine residues in the heavy chain of bevacizumab. Based on peptide mapping data, the acidic variant formation was attributed to deamidation of asparagine residue (N84), oxidation of M258, and preservation of C-terminal lysine residue, located on the heavy chain of bevacizumab. None of the observed charge heterogeneities in bevacizumab were due to differences in glycosylation among the variants. The basic (lysine) variants exhibited similar structural, functional, and stability profiles as the bevacizumab main product. But it was also noted that both the variants did not improve bevacizumab's therapeutic utility when pooled in different proportions with the main product. The acidic variant was found to have an equivalent secondary structure with subtle differences in the tertiary structure. The conformational difference also translated into a ~ 62% decrease in biological activity. Based on these data, it can be concluded that different charge variants behave differently with respect to their structure and bioactivity. Hence, biopharmaceutical manufacturers need to incorporate this understanding into their process and product development guidelines to maintain consistency in product quality.

10.
Nat Commun ; 12(1): 565, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495474

RESUMO

Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.


Assuntos
Neoplasias da Mama/prevenção & controle , Modelos Animais de Doenças , Jejum , Hiperinsulinismo/prevenção & controle , Obesidade/prevenção & controle , Pós-Menopausa/fisiologia , Animais , Neoplasias da Mama/sangue , Neoplasias da Mama/fisiopatologia , Restrição Calórica/métodos , Linhagem Celular Tumoral , Dieta Hiperlipídica , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/fisiopatologia , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/fisiopatologia , Ovariectomia , Pós-Menopausa/sangue
11.
Talanta ; 224: 121906, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379110

RESUMO

Human serum albumin (HSA) has pseudoesterase activity. So far on gel specific detection of such property of HSA is never reported. Moreover, protein binding dyes are non-specific for albumin. However, many of such dyes are used for HSA detection. So, dye-based albumin detection on the gel is expected to generate false-positive results for HSA. In this context, we have discovered that Fast Blue BB (FBBB, 0.12%) stains specifically HSA pseudoesterase activity with 2 Naphthyl acetate (2NA) as an ester substrate. Further, neostigmine has not inhibited the pseudoesterase activity associated with HSA. Neostigmine is a known inhibitor of many true esterases like acetylcholinesterase. So, neostigmine addition offers specificity to the method developed for staining of HSA. Additionally, 2NA stains HSA better than bovine serum albumin (BSA). Exploring all these novel findings, we have devised a simple method of HSA detection on the gel, accurately where other esterases are not detected. To the best of our knowledge, our method is the first to detect HSA pseudoesterase activity specifically on gel without getting interfered by any other esterase activity. The method detects HSA better than BSA. We feel that this method will go a long way for the specific detection of HSA on the gel. It is also relevant for understanding the purity of donor human milk matrix and pharmaceutical preparation of HSA. Our method can detect 7 µM of added HSA in human urine. Therefore, our method can be proceeded further for microalbuminuria detection in days to come.

12.
Ticks Tick Borne Dis ; 12(1): 101560, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007669

RESUMO

The gopher tortoise tick, Amblyomma tuberculatum, is known to parasitize keystone ectotherm reptile species. The biological success of ticks requires precise mechanisms to evade host hemostatic and immune responses. Acquisition of a full blood meal requires attachment, establishment of the blood pool, and engorgement of the tick. Tick saliva contains molecules which counter the host responses to allow uninterrupted feeding on the host. RNASeq of the salivary glands of Amblyomma tuberculatum ticks were sequenced resulting in 138,030 pyrosequencing reads which were assembled into 29,991 contigs. A total of 1875 coding sequences were deduced from the transcriptome assembly, including 602 putative secretory and 982 putative housekeeping proteins. The annotated data sets are available as a hyperlinked spreadsheet. The sialotranscriptome assembled for this tick species made available a valuable resource for mining novel pharmacological activities and comparative analysis.

13.
Mol Pharm ; 18(1): 124-147, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33346663

RESUMO

The rate and extent of drug release under physiological conditions is a key factor influencing the therapeutic activity of a formulation. Real-time detection of drug release by conventional pharmacokinetics approaches is confounded by low sensitivity, particularly in the case of tissue-targeted novel drug delivery systems, where low concentrations of the drug reach systemic circulation. We present a novel fluorescence turn-on platform for real-time monitoring of drug release from nanoparticles based on reversible fluorescence quenching in fluorescein esters. Fluorescein-conjugated carbon nanotubes (CNTs) were esterified with methotrexate in solution and solid phase, followed by supramolecular functionalization with a chemoenhancer (suramin) or/and a stealth agent (dextran sulfate). Suramin was found to increase the cytotoxicity of methotrexate in A549 cells. On the other hand, dextran sulfate exhibited no effect on cytotoxicity or cellular uptake of CNTs by A549 cells, while a decrease in cellular uptake of CNTs and cytotoxicity of methotrexate was observed in macrophages (RAW 264.7 cells). Similar results were also obtained when CNTs were replaced with graphene. Docking studies revealed that the conjugates are not internalized by folate receptors/transporters. Further, docking and molecular dynamics studies revealed the conjugates do not exhibit affinity toward the methotrexate target, dihydrofolate reductase. Molecular dynamics studies also revealed that distinct features of dextran-CNT and suramin-CNT interactions, characterized by π-π interactions between CNTs and dextran/suramin. Our study provides a simple, cost-effective, and scalable method for the synthesis of nanoparticles conferred with the ability to monitor drug release in real-time. This method could also be extended to other drugs and other types of nanoparticles.

14.
Micromachines (Basel) ; 11(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260829

RESUMO

In this paper, an efficient passive wireless harmonic communication system is proposed for the real-time monitoring of the pressurized pipelines. A pressure sensor is fabricated using the additive manufacturing technique and a harmonic radio frequency (RF) tag is designed to operate at the fundamental frequency (fo) of 2 GHz that shifts the phase of the back reflected RF signal according to the applied pressure ranging from 0 to 20 psi. A power efficient phase modulation with virtually no losses is achieved using a hybrid coupler-based phase shifter that efficiently reflect back the incoming signal using an end coupled reactive impedance element/sensor. The phase delay introduced by the reactive element gets doubled with the second harmonic communication, which increases the sensitivity by a factor of two. The concept of harmonic backscattering is exploited to reduce the effects of multi-path interference and self jamming, as well as improving the signal-to-noise ratio (SNR).

16.
Bioresour Technol ; 321: 124496, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33302013

RESUMO

In this review investigate the apple orchard waste (AOW) is potential organic resources to produce multi-product and there sustainable interventions with biorefineries approaches to assesses the apple farm industrial bioeconomy. The thermochemical and biological processes like anaerobic digestion, composting and , etc., that generate distinctive products like bio-chemicals, biofuels, biofertilizers, animal feed and biomaterial, etc can be employed for AOW valorization. Integrating these processes can enhanced the yield and resource recovery sustainably. Thus, employing biorefinery approaches with allied different methods can link to the progression of circular bioeconomy. This review article mainly focused on the different biological processes and thermochemical that can be occupied for the production of waste to-energy and multi-bio-product in a series of reaction based on sustainability. Therefore, the biorefinery for AOW move towards identification of the serious of the reaction with each individual thermochemical and biological processes for the conversion of one-dimensional providences to circular bioeconomy.

18.
PLoS One ; 15(12): e0244498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373390

RESUMO

The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains. Here, we used a metagenomic approach to sequence the 11 segments of RVA, RVC and RVH strains from piglets in the United States (US) and explore the evolutionary relations of these RV species. Metagenomics identified Astroviridae, Picornaviridae, Caliciviridae, Coronoviridae in samples MN9.65 and OK5.68 while Picobirnaviridae and Arteriviridae were only identified in sample OK5.68. Whole genome sequencing and phylogenetic analyses identified multiple genotypes with the RVA of strain MN9.65 and OK5.68, with the genome constellation of G5/G9-P[7]/P[13]-I5/I5- R1/R1-C1-M1-A8-N1-T7-E1/E1-H1 and G5/G9-P[6]/P[7]-I5-R1/R1-C1-M1-A8-N1-T1/T7-E1/E1-H1, respectively. The RVA strains had a complex evolutionary relationship with other mammalian strains. The RVC strain OK5.68 had a genome constellation of G9-P[6]-I1-R1-C5-M6-A5-N1-T1-E1-H1, and shared an evolutionary relationship with porcine strains from the US. The RVH strains MN9.65 and OK5.68 had the genome constellation of G5-P1-I1-R1-C1-M1-A5-N1-T1-E4-H1 and G5-P1-I1-R1-C1-M1-A5-N1-T1-E1-H1, indicating multiple RVH genome constellations are circulating in the US. These findings allow us to understand the complexity of the enteric virome, develop improved screening methods for RVC and RVH strains, facilitate expanded rotavirus surveillance in pigs, and increase our understanding of the origin and evolution of rotavirus species.

19.
J Cancer Res Ther ; 16(6): 1331-1335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33342792

RESUMO

Introduction: The role of hypofractionated radiotherapy (HFRT) in postmastectomy breast cancer patients is not well established. This study was done to establish the role of two different HFRT schedules in the treatment of chest wall and regional lymph nodes after mastectomy. Materials and Methods: Between 2012 and 2016, consecutively registered patients of locally advanced breast cancer patients having undergone mastectomy and adjuvant radiotherapy (RT) at a tertiary cancer center were analyzed. Locoregional recurrence (LRR) was the primary endpoint, whereas overall survival (OS), disease-free survival (DFS), and both acute and late adverse events were secondary endpoints. Results: A total of 34 patients who were treated with 39 Gy in 13 fractions over 2½ weeks and 35 patients who were treated with 40 Gy in 15 fractions over 3 weeks were identified. The median follow-up period was 47 months and 63.5 months in the 39 Gy and 40 Gy arms, respectively. LRR was seen in 11.8% and 8.6% of patients in the 39 Gy and 40 Gy arms, respectively. OS at 4 years was 66% and 71.5% in the 39 Gy and 40 Gy arms, respectively. The mean DFS for 39 Gy and 40 Gy arms was 43.6 months and 66.4 months, respectively (P = 0.822). Acute skin toxicity was similar in the two groups. Arm edema was significantly more in the 40 Gy arm. Conclusion: The two HFRT schedules are equivalent to each other in terms of survival outcomes. Arm edema is higher with 40 Gy arm as compared to 39 Gy arm.


Assuntos
Neoplasias da Mama/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Hipofracionamento da Dose de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Parede Torácica/efeitos da radiação
20.
Int J Biochem Cell Biol ; 130: 105885, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227392

RESUMO

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of TIPE/TNFAIP8 family, has been involved in the development and progression of various human cancers. We hypothesized that TNFAIP8 promotes prostate cancer (PCa) progression via regulation of oxidative phosphorylation (OXPHOS) and glycolysis. Ectopic expression of TNFAIP8 increased PCa cell proliferation/migration/spheroid formation by enhancing cell metabolic activities. Mechanistically, TNFAIP8 activated the PI3K-AKT pathway and up-regulated PCa cell survival. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with a glycolysis inhibitor, 2-deoxyglucose (2-DG), reduced TNFAIP8 mediated glucose consumption, ATP production, spheroid formation, and PCa cell migration. By maintaining mitochondrial membrane potential, TNFAIP8 increased OXPHOS and glycolysis. Moreover, TNFAIP8 modulates the production of glycolytic metabolites in PCa cells. Collectively, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells. Therefore, TNFAIP8 may be a biomarker associated with prostate cancer and indicate a potential therapeutic target.

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