444 research outputs found

    Nanomolecular detection of human influenza virus type A using reverse transcription loop-mediated isothermal amplification assisted with rod-shaped gold nanoparticles

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    Reverse transcription loop-mediated isothermal amplification (RT-LAMP) and rod-shaped gold nanoparticles (gold nanorods; GNRs) were employed for nanomolecular detection of human influenza virus type A RNA. After cDNA synthesis from the RNA, the primers targeting the M protein gene were used for LAMP amplification. A blue shift from red to purple from the GNR inserting into the LAMP-DNAs can be seen by the naked eye. Transmission electron microscopy revealed the formation GNR aggregates due to their interactions with LAMP DNA. One pg RNA (10-3 dilution of the viral cDNA) was detected using this colorimetric test. The nanomolecular test showed 100% sensitivity and 95.8% specificity in comparison to results by RT-PCR. Also, the test indicated 100% sensitivity and 100% specificity in comparison to results by RT-LAMP. The described nanomolecular test could detect human influenza virus type A RNA in nearly 1 hour. This journal is © the Partner Organisations 2014

    In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

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    Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

    Allelic polymorphism of insulin-like growth factor I gene and its association with production traits in native chickens

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    Insulin-like growth factor 1 (IGFI) is an essential regulator of growth, cell proliferation/differentiation and protein synthesis in a variety of cell types. IGFI is considered as one of the most important can-didate genes controlling production and reproduction traits in chickens. This locus could be linked to the highly effective genes affecting egg production and growth traits. The aim of present study was to investigate the IGFI gene polymorphism and its association with growth and egg production traits in Iranian native chicken. A total of 313 blood samples were collected from the Native poultry breeding centre, Khorasan province, Iran. Single nucleotide polymorphism (SNP) of the IGFI 5'-UTR was detected by PCR-RFLP method and PstI restriction endonuclease enzyme. Finally, the SNP was con-firmed by sequencing of RFLP profiles. Association between IGFI alleles and production traits was evaluated using multivariate regression analysis and GLM procedures. Two alleles A (PstI –) and B (PstI +) and three genotypes (A/A, A/B and B/B) were identified for the IGFI gene. Allele B was the most frequent (60.1%) and considered as reference allele for association study. A/B genotype was significantly correlated with lower first egg weight and higher egg laying intensity compared to B/B and A/A genotypes. No significant association was observed between IGFI genotypes and other pro-duction traits including egg weight, weight of sexual maturity and body weight. These results suggest that there is a possibility of IGFI genotypes acting as a genetic marker for selecting some egg produc-tion traits in native chickens

    Protection of hippocampal CA1 neurons against ischemia/Reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of Caspase-3 Activation

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    Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on atreadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

    The Role of N-Acetylcysteine in Platelet Aggregation and Reperfusion Injury in Recent Years

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    Introduction: N-acetylcysteine (NAC) is an amino acid that contains a cysteine group and is currently used widely in various fields of medical research especially in cardiology. In this review, potential benefits of NAC in the aggregation of platelet and reperfusion injury are evaluated. Methods and Results: The available evidence was collected by searching Scopus, Pub-Med, Medline, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Our searching was performed without time limitation and only English language articles were included in this review. Key words used as search terms included “N-acetylcysteine”, “platelet aggregation”, “reperfusion injury”. Over the past decade, several investigations were carried out to ascertain reperfusion injury and antiplatelet properties of NAC, and in this article the results of investigations in both models (human and animal) were addressed in details. The results revealed that NAC has an important antiplatelet property in animal models while this effect is not very significant in human models and needs more investigations. However, its reperfusion injury in both models is worth noticing. Conclusions: Due to the limited data about effectiveness of NAC in both human and animal as antiplatelet agent, more investigation is needed to evaluate NAC efficacy in platelet aggregation and reperfusion injury especially in human studies in the future

    Membrane fractioning of pre-treated waste activated sludge for the recovery of valuable biocompounds

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    The authors are grateful for the financial support from the Spanish Ministry of Science, Innovation and Universities through the projects MCIU-19-RTI2018-094218-B-I00 and MCIU-22-PID2021-125942OBI00. Authors also want to acknowledge the Employment, Industry and Tourism Office of the Principality of Asturias, Spain, for their financial support through the project AYUD/2021/51041. The author Daniel Núnez ˜ thanks the Principality of Asturias, Spain, for their financial support through the Severo Ochoa scholarship no BP19-093
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