In this paper, we have shown the existence of wandering domains as well as periodic domains with all possible combination under composition of transcendental entire functions in angular region using ...approximation theory.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to ...our surprise, suppression of KRAS increased autophagic flux, as did pharmacological inhibition of its effector ERK MAPK. Furthermore, we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. We speculated that ERK inhibition might thus enhance PDAC dependence on autophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to mediate antitumor activity in KRAS-driven PDAC. We conclude that combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition may be effective treatments for PDAC.
Glucocorticoid steroids are commonly prescribed for many inflammatory conditions, but chronic daily use produces adverse effects, including muscle wasting and weakness. In contrast, shorter ...glucocorticoid pulses may improve athletic performance, although the mechanisms remain unclear. Muscle is sexually dimorphic and comparatively little is known about how male and female muscles respond to glucocorticoids. We investigated the impact of once-weekly glucocorticoid exposure on skeletal muscle performance comparing male and female mice. One month of once-weekly glucocorticoid dosing improved muscle specific force in both males and females. Transcriptomic profiling of isolated myofibers identified a striking sexually dimorphic response to weekly glucocorticoids. Male myofibers had increased expression of genes in the IGF1/PI3K pathway and calcium handling, while female myofibers had profound upregulation of lipid metabolism genes. Muscles from weekly prednisone-treated males had improved calcium handling, while comparably treated female muscles had reduced intramuscular triglycerides. Consistent with altered lipid metabolism, weekly prednisone-treated female mice had greater endurance relative to controls. Using chromatin immunoprecipitation, we defined a sexually dimorphic chromatin landscape after weekly prednisone. These results demonstrate that weekly glucocorticoid exposure elicits distinct pathways in males versus females, resulting in enhanced performance.
•COD and TSS exceeded the prescribed criteria limit for drinking purpose.•HCO3 and SO4 were observed as the dominant anions.•Peculiar behaviour of SO4 was observed along the River ...Bhagirathi.•Significant correlation observed between flux and river discharge in Bhagirathi.
Himalayan rivers are considered the most sensitive of all the ecosystems to the impact of climate change. In the present investigation, hydrochemical processes controlling the meltwater chemistry of the rivers Bhagirathi, Alaknanda and Ganga in the Upper Ganga Basin, India have been studied simultaneously creating a large database for the first time. For this purpose, an extensive water quality assessment in Upper Ganga Basin has been carried out by collecting water samples from all three rivers on monthly basis from September 2016 to May 2018 and analysing these samples for hydro-chemical parameters. Hydro-chemical characteristics revealed that sulphide oxidation and carbonation- the two proton producing reactions govern the chemical weathering processes pertaining in the rivers. One of the most peculiar findings of the study is the dominance of carbonate dissolution in the whole stretch of River Alaknanda, while the dominance of sulphide oxidation in River Bhagirathi upto Dabrani revealing the continuum of Gangotri glacial processes followed by carbonate dissolution upto Haridwar. The principal component analysis further supports this weathering process in the basin.
Many cardiomyopathy-associated
pathogenic variants are heterozygous truncations, and
pathogenic variants are associated with arrhythmias. Arrhythmia triggers in filaminopathy are incompletely ...understood.
We describe an individual with biallelic
pathogenic variants, p.Arg650X and c.970-4A>G, with peripartum cardiomyopathy and ventricular arrhythmias. We also describe clinical findings in probands with
variants including Val2715fs87X, Glu2458Serfs71X, Phe106Leu, and c.970-4A>G with hypertrophic and dilated cardiomyopathy, atrial fibrillation, and ventricular tachycardia. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated. The
truncation, Arg650X/c.970-4A>G, showed a marked reduction in filamin C protein consistent with biallelic loss of function mutations. To assess loss of filamin C, gene editing of a healthy control iPSC line was used to generate a homozygous
disruption in the actin binding domain. Because filamin C has been linked to protein quality control, we assessed the necessity of filamin C in iPSC-CMs for response to the proteasome inhibitor bortezomib. After exposure to low-dose bortezomib,
null iPSC-CMs showed an increase in the chaperone proteins BAG3, HSP70 (heat shock protein 70), and HSPB8 (small heat shock protein B8) and in the autophagy marker LC3I/II.
null iPSC-CMs had prolonged electric field potential, which was further prolonged in the presence of low-dose bortezomib.
null engineered heart tissues had impaired function after low-dose bortezomib.
pathogenic variants associate with a predisposition to arrhythmias, which can be modeled in iPSC-CMs. Reduction of filamin C prolonged field potential, a surrogate for action potential, and with bortezomib-induced proteasome inhibition, reduced filamin C led to greater arrhythmia potential and impaired function.
Potato apical leaf curl disease is an emerging geminiviral disease in tropics and subtropics. It was reported for the first time in the year 1999 in northern plains of India but quickly spread to ...almost all potato growing regions of the country largely due to prevalence of warmer weather during early crop growth, thereby favoring whitefly vector. The problem of apical leaf curl disease in India became more severe due to lack of seed indexing for this virus in conventional seed production scheme. Although it accounts for major yield loss, there is no conventional source of resistance available in potato against
Tomato Leaf Curl New Delhi Virus-Potato
(ToLCNDV-Potato) that causes this disease in potato. In the present study, we have investigated the potential use of RNAi for obtaining resistance against this DNA virus in potato. The replication-associated protein gene (
AC1
) of the virus was used to obtain pathogen-derived resistance. The
AC1
gene was PCR amplified from field-infected potato leaves, cloned and sequenced (JN393309). It showed 93% sequence similarity with the
AC1
gene of
Tomato Leaf Curl Virus-New Delhi
(TOLCV-NDe; DQ169056) virus. Transgenic plants encoding the
AC1
gene in three different orientations, viz. sense, antisense and hairpin loop, were raised. Transgenic lines when challenge inoculated with ToLCNDV-Potato showed different levels of resistance for all three constructs. Transgene integration and copy number in selected transgenic lines were determined by qPCR and further confirmed by Southern blot analysis. Though a reduction in viral titer was observed in transgenic lines encoding either antisense or hairpin loop constructs of AC1 gene, the latter transgenics showed most significant results as shown by reduction in the level of symptom expression in glasshouse screening as well as real-time data of in vivo virus concentration. In fact, we obtained a few totally asymptomatic transgenic lines with hairpin loop strategy.
Levels of fast escaping sets were discussed by Rippon and Stallard. Here we have defined a set
) analogous to 0
level of fast escaping set by using maximum term and formation of spider’s web ...structure has been discussed for this set.
Abstract In this current study, hydrogels based on acacia gum (AG), polyacrylamide (PAM), and carboxymethyl tamarind kernel gum (CMTKG) were successfully developed and ciprofloxacin (drug) ...incorporated into it. To optimize the hydrogel, the concentrations of crosslinker and initiator were varied, and their effects on the swelling were examined. The hydrogel was subjected to characterization techniques such as Powder X‐ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Attenuated Total Reflection‐Fourier Transform Infrared spectroscopy (ATR‐FTIR), and Thermogravimetric analysis (TGA). The hydrogel swelling and in vitro drug release were assessed in pH 1.2 and 7.4 buffer solutions. The findings revealed that an alkaline pH yielded superior results for the swelling and in vitro drug release experiments compared to an acidic pH. The drug release kinetic of the ciprofloxacin‐loaded AG/PAM/CMTKG hydrogel followed the Korsmeyer–Peppas model, demonstrating non‐fickian diffusion at pH 7.4 and fickian mechanism at pH 1.2. The pH‐dependent behavior of ciprofloxacin‐loaded AG/PAM/CMTKG hydrogel displayed its potential implications for site‐specific ciprofloxacin release.
Let f be a transcendental entire function and let I(f) be the points which escape to infinity under iteration. Bergweiler and Hinkkanen introduced the fast escaping sets A(f) and subsequently, Rippon ...and Stallard introduced `Levels' of fast escaping sets . These sets under some restriction have the properties of "infinite spider's web" structure. Here we give some topological properties of the infinite spider's web and show some of the transcendental entire functions whose levels of the fast escaping sets have infinite spider's web structure.
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