The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the ...uptake of choline (choline transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyltransferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetylcholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic cigarettes considered by many as a “safe” alternative to smoking. There are a small number of articles which review the contribution of the other cholinergic proteins in the pathophysiology of lung cancer. The primary objective of this review article is to discuss the function of the acetylcholine-signaling proteins in the progression of lung cancer. The investigation of the role of cholinergic network in lung cancer will pave the way to novel molecular targets and drugs in this lethal malignancy.
Culture & European attitudes on public debt Aspide, Alessia; Brown, Kathleen J.; DiGiuseppe, Matthew ...
New political economy,
07/2023, Letnik:
28, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Popular media and politicians have often blamed the high public debt of some EU countries on cultural differences. These claims are most apparent in the discourse contrasting ostensibly prudent ...Northern Europeans with spendthrift Southern Europeans. Despite the prominence of these and similar narratives and evidence that culture plays a nontrivial role in other economic outcomes, there is no systematic evidence that culture influences attitudes towards sovereign debt in the EU. We provide the first empirical test of this claim using over 233,000 responses to a Eurobarometer question about the salience of national debt. Our analysis reveals that national and sub-national differences explain very little of the variance in debt preferences. Further, the differences that do emerge do not fit existing cultural narratives. Additional analysis reveals that established measures of national culture or religious observance, at the national and regional levels, do not correlate with debt attitudes as cultural arguments would predict.
Drought is a major source of yield loss in the production of rice (
Oryza sativa
L.), and cultivars that maintain yield under drought across environments and drought stress scenarios are urgently ...needed. Root phenotypes directly affect water interception and uptake, so plants with root systems optimized for water uptake under drought would likely exhibit reduced yield loss. Deeper nodal roots that have a low metabolic cost per length (i.e., cheaper roots)
via
smaller root diameter and/or more aerenchyma and that transport water efficiently through smaller diameter metaxylem vessels may be beneficial during drought. Subsets of the Rice Diversity Panel 1 and Azucena × IR64 recombinant inbred lines were grown in two greenhouse and two rainout shelter experiments under drought stress to assess their shoot, root anatomical, and root architectural phenotypes. Root traits and root trait plasticity in response to drought varied with genotype and environment. The best-performing groups in the rainout shelter experiments had less plasticity of living tissue area in nodal roots than the worst performing groups. Root traits under drought were partitioned into similar groups or clusters
via
the partitioning-around-medoids algorithm, and this revealed two favorable integrated root phenotypes common within and across environments. One favorable integrated phenotype exhibited many, deep nodal roots with larger root cross-sectional area and more aerenchyma, while the other favorable phenotype exhibited many, deep nodal roots with small root cross-sectional area and small metaxylem vessels. Deeper roots with high theoretical axial hydraulic conductance combined with reduced root metabolic cost contributed to greater shoot biomass under drought. These results reflect how some root anatomical and architectural phenes work in concert as integrated phenotypes to influence the performance of plant under drought stress. Multiple integrated root phenotypes are therefore recommended to be selected in breeding programs for improving rice yield across diverse environments and drought scenarios.
A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in ...18 individuals, with p.Arg87 substitutions in the majority.
We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC.
Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype-phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts.
Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism.
Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital associated kidney damage. Potential mechanisms of CI-AKI may involve diminished renal hemodynamics, ...inflammatory responses, and direct cytotoxicity. The hypothesis for this study is that diatrizoic acid (DA) induces direct cytotoxicity to human proximal tubule (HK-2) cells via calcium dysregulation, mitochondrial dysfunction, and oxidative stress. HK-2 cells were exposed to 0-30 mg I/mL DA or vehicle for 2-24 h. Conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion indicated a decrease in mitochondrial and cell viability within 2 and 24 h, respectively. Mitochondrial dysfunction was apparent within 8 h post exposure to 15 mg I/mL DA as shown by Seahorse XF cell mito and Glycolysis Stress tests. Mitophagy was increased at 8 h by 15 mg I/mL DA as confirmed by elevated LC3BII/I expression ratio. HK-2 cells pretreated with calcium level modulators BAPTA-AM, EGTA, or 2-aminophenyl borinate abrogated DA-induced mitochondrial damage. DA increased oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4HNE) adduct formation. Caspase 3 and 12 activation was induced by DA compared to vehicle at 24 h. These studies indicate that clinically relevant concentrations of DA impair HK-2 cells by dysregulating calcium, inducing mitochondrial turnover and oxidative stress, and activating apoptosis.
Cancer progression is a complex multistep process comprising of angiogenesis of the primary tumor, its invasion into the surrounding stroma and its migration to distant organs to produce metastases. ...Nutritional compounds of the “capsaicinoid” family regulate angiogenesis, invasion and metastasis of tumors. Capsaicinoids display robust anti-angiogenic activity in both cell culture and mice models. However, conflicting reports exist about the effect of capsaicinoids on invasion of metastasis of cancers. While some published reports have described an anti-invasive and anti-metastatic role for capsaicinoids, others have argued that capsaicinoids stimulate invasion and metastasis of cancers. The present review article summarizes these findings involving the bioactivity of capsaicin in angiogenesis, invasion and metastasis of cancer. A survey of literature indicate that they are several articles summarizing the growth-inhibitory activity of capsaicinoids but few describe its effects on angiogenesis, invasion and metastasis in detail. Our review article fills this gap of knowledge. The discovery of a second generation of natural and synthetic capsaicin analogs (with anti-tumor activity) will pave the way to improved strategies for the treatment of several human cancers.
Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and ...Drug Administration approved for this indication.
To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.
This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam.
Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered.
The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration.
Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%).
Among pediatric patients with convulsive status epilepticus, treatment with lorazepam did not result in improved efficacy or safety compared with diazepam. These findings do not support the preferential use of lorazepam for this condition.
clinicaltrials.gov Identifier: NCT00621478.
Background and aims RootScan is a program for semi-automated image analysis of anatomical traits in root cross-sections. Methods RootScan uses pixel thresholds to separate the cross-section from its ...background and to divide it into tissue regions. Area measurements and object counts are performed within various regions of interest. A graphical user interface permits the user to see which regions are selected, to edit those selections, and to rate and comment on the data. The structure of the program allows for organized workflow and increased data collection efficiency. Results The program collects data on more than 20 variables per image including areas of the cross-section, stele, cortex, aerenchyma lacunae, xylem vessels, and counts of cortical cells and cell files. An increased rate of data collection allows collection of four times more variables in less time than is possible with current methods. Correlation analysis shows that RootScan data is equal or greater in accuracy than data collected with Photoshop. Conclusions Compared with currently available tools, this software offers considerable improvements in the amount and quality of data, ease of use, and time needed for data collection. RootScan permits phenotypic scoring of physiologically and agronomically important traits on a large number of genotypes.
Low phosphorus availability is a primary constraint to plant productivity in many natural and agricultural ecosystems. Plants display a wide array of adaptive responses to low phosphorus availability ...that generally serve to enhance phosphorus mobility in the soil and increase its uptake. One set of adaptive responses is the alteration of root architecture to increase phosphorus acquisition from the soil at minimum metabolic cost. In a series of studies with the common bean, work in our laboratory has shown that architectural traits that enhance topsoil foraging appear to be particularly important for genotypic adaptation to low phosphorus soils ('phosphorus efficiency'). In particular, the gravitropic trajectory of basal roots, adventitious rooting, the dispersion of lateral roots, and the plasticity of these processes in response to phosphorus availability contribute to phosphorus efficiency in this species. These traits enhance the exploration and exploitation of shallow soil horizons, where phosphorus availability is greatest in many soils. Studies with computer models of root architecture show that root systems with enhanced topsoil foraging acquire phosphorus more efficiently than others of equivalent size. Comparisons of contrasting genotypes in controlled environments and in the field show that plants with better topsoil foraging have superior phosphorus acquisition and growth in low phosphorus soils. It appears that many architectural responses to phosphorus stress may be mediated by the plant hormone ethylene. Genetic mapping of these traits shows that they are quantitatively inherited but can be tagged with QTLs that can be used in plant breeding programs. New crop genotypes incorporating these traits have substantially improved yield in low phosphorus soils, and are being deployed in Africa and Latin America.
Purpose
: This study explores the effects of an alternative, transformative andragogy (i.e., the art and science of helping others to learn) designed to be responsive to the challenges of preparing ...educational leaders committed to social justice and equity.
Design
: Within the context of preparation programs, the three theoretical perspectives of adult learning theory, transformative learning theory, and critical social theory are interwoven with the three andragogical processes of critical reflection, rational discourse, and policy praxis to form an alternative, transformative framework. Forty graduate students of educational administration (two cohorts of preservice leaders) participated in this study. Quantitative methods are used to assess the possible effects of transformative learning strategies on preservice leaders' attitudes toward issues of diversity in education. Qualitative research methods are then employed to further explore the possible effects of andragogical approaches on preservice leaders' personal beliefs and their reported ability to connect theory to practice.
Findings
: Findings indicate that participation in transformative learning processes and strategies can increase students' perceived growth in awareness, acknowledgement, and action toward social justice.
Implications
: The strategies used were created to help future leaders develop as transformative, reflective scholars and practitioners actively engaged in political, emancipatory interests. By participating in a number of assignments requiring the examination of ontological and epistemological assumptions, values and beliefs, context and experience, and competing worldviews, transformation is possible.
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