A new and novel approach has been adopted in this study to evaluate thermal mismatch induced by thermal expansion in substrate-coating contact pairs using in-situ high-temperature X-ray diffraction ...(HT-XRD). Atmospheric plasma sprayed (APS) Mn1.0Co1.9Fe0.1O4(MCF) coating on Crofer 22 APU steel interconnect was investigated. In-situ HT-XRD was performed individually for substrate and coating from 25 °C to 900 °C. Diffraction data were recorded for different temperatures to obtain lattice parameters and strain as a function of temperature. The coefficient of thermal expansion (CTE) of MCF coating was slightly higher than steel substrate and showed no significant thermal expansion mismatch till 700 °C. The increasing lattice strain measured by Scherrer and Williamson-Hall methods indicates strain-induced phase transformation of MCF coating with temperature, supporting the phase transformation-induced self-healing phenomenon of MCF coating. The merit of in-situ HT-XRD as a tool for optimizing operating temperature and measuring thermal mismatch of solid oxide fuel cell (SOFC) stacks has been discussed.
•The in-situ HT-XRD method was used to evaluate thermal expansion compatibility of spinel coated Crofer 22 APU steel.•The CTE of plasma sprayed spinel coating and Crofer steel was found to be closer and highly compatible.•The coating-substrate thermal mismatch was significant above 700 °C.•The strain-induced phase transformation of spinel coating results in the thermal mismatch.
It is generally believed that the miRNA processing machinery ensures the generation of a mature miRNA with a fixed sequence, particularly at its 5' end. However, we and others have recently noted ...that the ends of a given mature miRNA are not absolutely fixed, but subject to variation. Neither the significance nor the mechanism behind the generation of such miRNA polymorphism is understood. miR-142 is an abundantly expressed miRNA in hematopoietic cells and exhibits a high frequency of 5' end polymorphism.
Here we show that a shift in the Drosha processing of pri-miRNA generates multiple forms of miR-142s in vivo with differing 5' ends that might target different genes. Sequence analysis of several pre-miRNA ends cloned from T cells reveals that unlike many other pri-miRNAs that are processed into a single pre-miRNA, pri-miR-142 is processed into 3 distinct pre-miR-142s. Dicer processing studies suggest that each of the 3 pre-miR-142s is processed into a distinct double-stranded miRNA, giving rise to 4 mature miRNA variants that might regulate different target gene pools.
Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract In mammalian cells, proteins involved in mRNA silencing and degradation localize to discrete cytoplasmic foci called processing or P-bodies. Here we show that microscopically visible ...P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3. Kinetic studies suggest that the component proteins are first released from P-bodies in response to WNV infection within 12 h post-infection, followed by recruitment to the viral replication sites by 24–36 h post-infection. Silencing of the recruited proteins individually with siRNA interfered with viral replication to varying extents suggesting that the recruited proteins are required for efficient viral replication. Thus, the P-body proteins might provide novel drug targets for inhibiting viral infection.
RNA interference (RNAi) provides a powerful tool to silence specific gene expression and has been widely used to suppress host factors such as CCR5 and/or viral genes involved in HIV-1 replication. ...Newer nuclease-based gene-editing technologies, such as zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, also provide powerful tools to ablate specific genes. Because of differences in co-receptor usage and the high mutability of the HIV-1 genome, a combination of host factors and viral genes needs to be suppressed for effective prevention and treatment of HIV-1 infection. Whereas the continued presence of small interfering/short hairpin RNA (si/shRNA) mediators is needed for RNAi to be effective, the continued expression of nucleases in the gene-editing systems is undesirable. Thus, RNAi provides the only practical way for expression of multiple silencers in infected and uninfected cells, which is needed for effective prevention/treatment of infection. There have been several advances in the RNAi field in terms of si/shRNA design, targeted delivery to HIV-1 susceptible cells, and testing for efficacy in preclinical humanized mouse models. Here, we comprehensively review the latest advances in RNAi technology towards prevention and treatment of HIV-1.
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The recent development of robust indices to quantify biological aging, along with the dynamic epidemiological transitions of population aging generate the unmet need to examine the extent up to which ...potential interventions can delay, halt or temporarily modulate aging trajectories.
The study is a two-armed, open label randomised controlled trial. We aim to recruit 166 subjects, aged 60-75 years from the residential communities and old age clubs in Bangalore city, India, who will undergo randomisation into intervention or control arms (1:1). Intervention will include yoga sessions tailored for the older adults, 1 h per day for 5 days a week, spread for 12 months. Data would be collected at the baseline, 26
week and 52
week. The primary outcome of the study is estimation in biological age with yoga practice. The secondary outcomes will include cardinal mechanistic indicators of aging- telomere length, interleukin-6 (IL-6), tumor necrosis factor receptor II (TNF-RII), high sensitivity c-reactive protein (hsCRP), insulin signaling insulin and IGF1, renal function cystatin, senescence growth differentiating factor 15 (GDF-15) and cardiovascular function N-terminal B-type natriuretic peptides (NT-proBNP). Analyses will be by intention-to-treat model.
The study is approved by the Institutional Ethics Committee of Swami Vivekananda Yoga Anusandhana Samsthana University, Bangalore (ID:RES/IEC-SVYASA/242/2022). Written informed consent will be obtained from each participant prior to inclusion.
CTRI/2022/07/044442.
West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a ...library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death.
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•A knockout screening method based on CRISPR-Cas9•Two rounds of screening improve sensitivity and specificity•Seven genes of the ERAD pathway are essential for WNV-induced cell death•These genes connect WNV replication to ensuing cell death
Ma et al. use a CRISPR-based genome-wide knockout screening method to identify seven genes linked to ER-associated degradation (ERAD) as factors involved in West Nile virus (WNV)-induced cell death.
A major impediment in the treatment of neurological diseases is the presence of the blood-brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a ...short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA (siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood-brain barrier.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: Continuous thoracic epidural analgesia (TEA) is compared with erector spinae plane (ESP) block for the perioperative pain management in patients undergoing cardiac surgery for the quality ...of analgesia, incentive spirometry, ventilator duration, and intensive care unit (ICU) duration. Methodology: A prospective, randomized comparative clinical study was conducted. A total of 50 patients were enrolled, who were randomized to either Group A: TEA (n = 25) or Group B: ESP block (n = 25). Visual analog scale (VAS) was recorded in both the groups during rest and cough at the various time intervals postextubation. Both the groups were also compared for incentive spirometry, ventilator, and ICU duration. Statistical analysis was performed using the independent Student's t-test. A value of P < 0.05 was considered statistically significant. Results: C omparable VAS scores were revealed at 0 h, 3 h, 6 h, and 12 h (P > 0.05) at rest and during cough in both the groups. Group A had a statistically significant VAS score than Group B (P ≤ 0.05) at 24 h, 36 h, and 48 h but mean VAS in either of the Group was ≤4 both at rest and during cough. Incentive spirometry, ventilator, and ICU duration were comparable between the groups. Conclusion: ESP block is easy to perform and can serve as a promising alternative to TEA in optimal perioperative pain management in cardiac surgery.
The bioconvection flow of tiny fluid conveying the nanoparticles has been investigated between two concentric cylinders. The contribution of Lorenz force is also focused to inspect the bioconvection ...thermal transport of tiny particles. The tiny particles are assumed to flow between two concentric cylinders of different radii. The first cylinder remains at rest while flow is induced due to second cylinder which rotates with uniform velocity. Furthermore, the movement of tiny particles follows the principle of thermophoresis and Brownian motion as a part of thermal and mass gradient. Similarly, the gyro-tactic microorganisms swim in the nanofluid as a response to the density gradient and constitute bio-convection. The problem is modeled by using the certain laws. The numerical outcomes are computed by using RKF -45 method. The graphical simulations are performed for flow parameters with specific range like 1≤Re≤5, 1≤Ha≤5, 0.5≤Nt≤2.5, 1≤Nb≤3, 0.2≤Sc≤1.8, 0.2≤Pe≤1.0 and 0.2≤Ω≤1.0. It is observed that the flow velocity decreases with the increase in the Hartmann number that signifies the magnetic field. This outcome indicates that the flow velocity can be controlled externally through the magnetic field. Also, the increase in the Schmidt numbers increases the nanoparticle concentration and the motile density.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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