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"Engel, J -P."
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Bilingualism Enriches the Poor: Enhanced Cognitive Control in Low-Income Minority Children
This study explores whether the cognitive advantage associated with bilingualism in executive functioning extends to young immigrant children challenged by poverty and, if it does, which specific processes are most affected. In the study reported here, 40 Portuguese-Luxembourgish bilingual children from low-income immigrant families in Luxembourg and 40 matched monolingual children from Portugal completed visuospatial tests of working memory, abstract reasoning, selective attention, and interference suppression. Two broad cognitive factors of executive functioning—representation (abstract reasoning and working memory) and control (selective attention and interference suppression)—emerged from principal component analysis. Whereas there were no group differences in representation, the bilinguals performed significantly better than did the monolinguals in control. These results demonstrate, first, that the bilingual advantage is neither confounded with nor limited by socioeconomic and cultural factors and, second, that separable aspects of executive functioning are differentially affected by bilingualism. The bilingual advantage lies in control but not in visuospatial representational processes.
Journal Article
Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma
While mutations in the
KRAS
oncogene are among the most prevalent in human cancer, there are few successful treatments to target these tumors. It is also likely that heterogeneity in
KRAS
-mutant tumor biology significantly contributes to the response to therapy. We hypothesized that the presence of commonly co-occurring mutations in
STK11
and
TP53
tumor suppressors may represent a significant source of heterogeneity in
KRAS
-mutant tumors. To address this, we utilized a large cohort of resected tumors from 442 lung adenocarcinoma patients with data including annotation of prevalent driver mutations (
KRAS
and
EGFR)
and tumor suppressor mutations (
STK11
and
TP53
), microarray-based gene expression and clinical covariates, including overall survival (OS). Specifically, we determined impact of
STK11
and
TP53
mutations on a new
KRAS
mutation-associated gene expression signature as well as previously defined signatures of tumor cell proliferation and immune surveillance responses. Interestingly,
STK11
, but not
TP53
mutations, were associated with highly elevated expression of
KRAS
mutation-associated genes. Mutations in
TP53
and
STK11
also impacted tumor biology regardless of
KRAS
status, with
TP53
strongly associated with enhanced proliferation and
STK11
with suppression of immune surveillance. These findings illustrate the remarkably distinct ways through which tumor suppressor mutations may contribute to heterogeneity in
KRAS
-mutant tumor biology. In addition, these studies point to novel associations between gene mutations and immune surveillance that could impact the response to immunotherapy.
Journal Article
Antonio Gramsci
\"Antonio Gramsci is a giant of Marxian thought and one of the world's greatest cultural critics. Antonio A. Santucci is perhaps the world's preeminent Gramsci scholar. Monthly Review Press is proud to publish, for the first time in English, Santucci's masterful intellectual biography of the great Sardinian scholar and revolutionary. Gramscian terms such as 'civil society' and 'hegemony' are much used in everyday political discourse. Santucci warns us, however, that these words have been appropriated by both radicals and conservatives for contemporary and often self-serving ends that often have nothing to do with Gramsci's purposes in developing them. Rather what we must do, and what Santucci illustrates time and again in his dissection of Gramsci's writings, is absorb Gramsci's methods.\" -- Publisher description.
Book
Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane
Fibrillar protein deposits (amyloid) in the pancreatic islets of Langerhans are thought to be involved in death of the insulin-producing islet β cells in type 2 diabetes mellitus. It has been suggested that the mechanism of this β cell death involves membrane disruption by human islet amyloid polypeptide (hIAPP), the major constituent of islet amyloid. However, the molecular mechanism of hIAPP-induced membrane disruption is not known. Here, we propose a hypothesis that growth of hIAPP fibrils at the membrane causes membrane damage. We studied the kinetics of hIAPP-induced membrane damage in relation to hIAPP fibril growth and found that the kinetic profile of hIAPP-induced membrane damage is characterized by a lag phase and a sigmoidal transition, which matches the kinetic profile of hIAPP fibril growth. The observation that seeding accelerates membrane damage supports the hypothesis. In addition, variables that are well known to affect hIAPP fibril formation, i.e., the presence of a fibril formation inhibitor, hIAPP concentration, and lipid composition, were found to have the same effect on hIAPP-induced membrane damage. Furthermore, electron microscopy analysis showed that hIAPP fibrils line the surface of distorted phospholipid vesicles, in agreement with the notion that hIAPP fibril growth at the membrane and membrane damage are physically connected. Together, these observations point toward a mechanism in which growth of hIAPP fibrils, rather than a particular hIAPP species, is responsible for the observed membrane damage. This hypothesis provides an additional mechanism next to the previously proposed role of oligomers as the main cytotoxic species of amyloidogenic proteins.
Journal Article
How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials
We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (−0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat=6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES=−0.39), positive symptoms (ES=−0.48), depression (ES=−0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs
and
the scarcity of adverse event differences compared with placebo needs to be established.
Journal Article
Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia
Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼10(11) viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January.
Journal Article
The Glucagon-Like Peptide 1 Analogue, Exendin-4, Attenuates the Rewarding Properties of Psychostimulant Drugs in Mice
Glucagon-like peptide 1 (GLP-1) is an incretine hormone that controls consummatory behavior and glucose homeostasis. It is released in response to nutrient ingestion from the intestine and production in the brain has also been identified. Given that GLP-1 receptors are expressed in reward areas, such as the nucleus accumbens and ventral tegmental area, and that common mechanisms regulate food and drug-induced reward we hypothesize that GLP-1 receptors are involved in reward regulation. Herein the effect of the GLP-1 receptor agonist Exendin-4 (Ex4), on amphetamine- and cocaine-induced activation of the mesolimbic dopamine system was investigated in mice. In a series of experiments we show that treatment with Ex4, at a dose with no effect per se, reduce amphetamine- as well as cocaine-induced locomotor stimulation, accumbal dopamine release as well as conditioned place preference in mice. Collectively these data propose a role for GLP-1 receptors in regulating drug reward. Moreover, the GLP-1 signaling system may be involved in the development of drug dependence since the rewarding effects of addictive drugs involves interferences with the mesolimbic dopamine system. Given that GLP-1 analogues, such as exenatide and liraglutide, are clinically available for treatment of type II diabetes, we propose that these should be elucidated as treatments of drug dependence.
Journal Article
Treat-to-target (T2T) recommendations for gout
ObjectivesThe treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout.MethodsA committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived.ResultsAlthough no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance.ConclusionsThis is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.
Journal Article