bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational readthrough goes unseen by natural selection
Authors: Kleppe April Snofrid , Bornberg-Bauer Erich 
Published: November 2019

AbstractOccasionally during protein synthesis, the ribosome bypasses the stop codon and continues translation to the next stop codon in frame. This error is called translational readthrough (TR). Earlier research suggest that TR is a relatively common error, in several taxa, yet the evolutionary relevance of this translational error is still unclear. By analysing ribosome profiling data, we have conducted species comparisons between yeasts to infer conservation of TR between orthologs. Moreover, we infer the evolutionary rate of error prone and canonically translated proteins to deduct differential selective pressure. We find that about 40% of error prone proteins in Schizosaccharomyces pombe do not have any orthologs in Saccharomyces cerevisiae, but that 60% of error prone proteins in S. pombe are undergoing canonical translation in S. cerevisiae. Error prone proteins tend to have a higher GC-content in the 3’-UTR, unlike their canonically translated ortholog. We do not find the same trends for GC-content of the CDS. We discuss the role of 3’-UTR and GC-content regarding translational readthrough. Moreover, we find that there is neither selective pressure against or for TR. We suggest that TR is a near-neutral error that goes unseen by natural selection. We speculate that TR yield neutral protein isoforms that are not being purged. We suggest that isoforms, yielded by TR, increase proteomic diversity in the cell, which is readily available upon sudden environmental shifts and which therefore may become adaptive.Author SummaryThere is an evolutionary balance act between adaptation and selection against change. Any system needs to be able to adapt facing novel environmental conditions. Simultaneously, biological systems are under selection to maintain fitness and thus undergo selection against mutations. Phenotypic mutations - translational errors during protein synthesis - have been suggested to play a role in protein evolvability by enabling quick assessment of viable phenotypes and thus enable quick adaptation. Here we test this hypothesis, by inferring evolutionary rate of proteins prone to a specific case of phenotypic mutations: translational readthrough (TR). By making use of publicly available data of yeasts, we find that TR goes unseen by natural selection and appear as a neutral event. We suggest that TR goes unseen by selection and occurs as “permissive wallflowers”, which may become relevant and yield adaptive benefits. This work highlights that stochastic processes are not necessarily under stringent selection but may prevail. In conclusion, we suggest that TR is a neutral non-adaptive process that can yield adaptive benefits.
Seasonal and annual fluctuations of deer populations estimated by a Bayesian state–space model
Authors: Mizuki Inoue , Itô Hiroki , Yamasaki Michimasa , Fukumoto Shigeru , Okamoto Yuuki , Katsuki Masaya , Fukushima Keitaro , Sakai Masaru , Sakaguchi Shota , Fujiki Daisuke , Nakagawa Hikaru , Ishihara Masae , Takayanagi Atsushi 
Published: November 2019

AbstractDeer overabundance is a contributing factor in the degradation of plant communities and ecosystems worldwide. The management and conservation of the deer-affected ecosystems requires us to urgently grasp deer population trends and to identify the factors that affect them. In this study, we developed a Bayesian state–space model to estimate the population dynamics of sika deer (Cervus nippon) in a cool-temperate forest in Japan, where wolves (Canis lupus hodophilax) are extinct. The model was based on field data collected from block count surveys, road count surveys by vehicles, mortality surveys during the winter, and nuisance control for 12 years (2007–2018). We clarified the seasonal and annual fluctuation of the deer population. We found two peaks of deer abundance (2007 and 2010) over 12 years. In 2011 the estimated deer abundance decreased drastically and has remained at a low level then. The deer population increased from spring to autumn and decreased from autumn to winter in most years. The seasonal fluctuation we detected could reflect the seasonal migration pattern of deer and the population recruitment through fawn births in early summer. In our model, snowfall accumulation, which can be a lethal factor for deer, may have slightly affected their mortality during the winter. Although we could not detect a direct effect of snow on population dynamics, snowfall decrease due to global warming may decelerate the winter migration of deer; subsequently, deer staying on-site may intensively forage evergreen perennial plants during the winter season. The nuisance control affected population dynamics. Even in wildlife protection areas and national parks where hunting is regulated, nuisance control could be effective in buffering the effect of deer browsing on forest ecosystems.
Real-time measurement of E2:ERα transcriptional activity in living cells
Authors: Cipolletti Manuela , Leone Stefano , Bartoloni Stefania , Busonero Claudia , Acconcia Filippo 
Published: November 2019

AbstractKinetic analyses of diverse physiological processes have the potential to unveil new aspects of the molecular regulation of cell biology at temporal levels. 17β-estradiol (E2) regulates diverse physiological effects by binding to the estrogen receptor α (ERα), which primarily works as a transcription factor. Although many molecular details of the modulation of ERα transcriptional activity have been discovered including the impact of receptor plasma membrane localization and its relative E2-evoked signalling, the knowledge of real-time ERα transcriptional dynamics in living cells is lacking. Here, we report the generation of MCF-7 and HeLa cells stably expressing a modified luciferase under the control of an E2-sensitive promoter, which activity can be continuously monitored in living cells and show that E2 induces a linear increase in ERα transcriptional activity. Ligand-independent (e.g., epidermal growth factor) receptor activation was also detected in a time-dependent manner. Kinetic profiles of ERα transcriptional activity measured in the presence of both receptor antagonists and inhibitors of ERα plasma membrane localization reveals a biphasic dynamic of receptor behaviour underlying novel aspects of receptor-regulated transcriptional effects. Finally, analysis of the rate of the dose-dependent E2 induction of ERα transcriptional activity demonstrates that low doses of E2 induce an effect identical to that determined by high concentrations of E2 as a function of the duration of hormone administration. Overall, we present the characterization of sensitive stable cell lines where to study the kinetic of E2 transcriptional signaling and to identify new aspects of ERα function in different physiological or pathophysiological conditions.
Introduced species dominate different responses of grassland communities to climate change on serpentine and nonserpentine soils
Authors: Braasch Joseph E , Johnson Maria A , Harrison Susan P , Dlugosch Katrina M 
Published: November 2019

AbstractIntroduced species are a common feature of modern plant communities and experience environmental challenges alongside native species. Changes to the environment may reveal distinct species-environment relationships for native and introduced components of plant communities. Extreme environmental change, such as drought, is predicted to result in declines in native species and increased opportunities for invasion, but empirical support for these ideas remains mixed. We tested for differences in the response of native and invaded species to environmental changes by analyzing a longterm dataset of species abundance in California grasslands collected during a period of severe drought. Sampling sites included a combination of stressful serpentine soils, which are resilient against invasion and maintain diverse native species assemblages, and more benign nonserpentine soils, which are heavily invaded and harbor low levels of native species cover. We found a significant correlation between sampling year and species composition for nonserpentine sites, but not for serpentine sites. These patterns were repeated when only introduced species were included in the analysis but no pattern of change was found for native species. The species most strongly associated with directional change on nonserpentine soils were three invasive Eurasian grasses, Bromus hordaceus, Taeniatherium caput-medusae, and Avena fatua. Differences in species composition on both serpentine and nonserpentine soils were significantly correlated with specific leaf area, a trait which has been linked to drought tolerance in these communities, although changes in abundance for the three Eurasian grasses most strongly associated with change did not consistently follow this pattern. Our analyses indicate relatively stable native community composition and strong directional change in introduced species composition, contradicting predictions for how native and introduced species will respond to environmental shifts, but supporting the hypothesis that native and invading species groups have important functional differences that shape their relationships to the environment.
Inhibition of both mutant and wild-type RAS-GTP in KRAS G12C colorectal cancer through cotreatment with G12C and EGFR inhibitors
Authors: McFall Thomas , Trogdon Michael , Sisk-Hackworth Laura , Stites Edward C. 
Published: November 2019

ABSTRACTThe combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we reveal a new benefit of this combination: it effectively inhibits both wild-type and mutant RAS. A role for WT RAS inhibition has not previously been reported for this important combination of targeted therapies. We believe that targeting both mutant and wild-type RAS helps explain why this combination of inhibitors is effective.
MiR‐29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1
Authors: Wang Ruili , Yang Ying , Wang Hui , He Ya , Li Chen 
Published: November 2019

AbstractMicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR‐29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP‐treated mice or MPP+‐intoxicated SH‐SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR‐29c was employed to examine its biological function on PD progress. We found that miR‐29c was down‐expressed but SP1 was high‐expressed in substantia nigra pars compacta (SNpc) of MPTP‐induced PD mice. Overexpression of miR‐29c attenuated dopaminergic neuron loss and α‐synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro‐inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) and TUNEL‐positive apoptotic cells in MPTP‐treated mice were ameliorated by miR‐29c. Similarly, in SH‐SY5Y cell models of PD, we also found that miR‐29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro‐apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR‐29c. Luciferase reporter assay confirmed that SP1 was complementary with miR‐29c. Knockdown of SP1 with siRNA restored α‐synuclein accumulation, inflammation and apoptosis in MPP+‐induced SH‐SY5Y cells. Collectively, this current work presents that miR‐29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.
The loss of NMDAR‐dependent LTD following cannabinoid self‐administration is restored by positive allosteric modulation of CB1 receptors
Authors: Neuhofer Daniela , Spencer Sade M. , Chioma Vivian C. , Beloate Lauren N. , Schwartz Danielle , Kalivas Peter W. 
Published: November 2019

AbstractGlutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self‐administration. We used intravenous self‐administration of two constituents of cannabis, Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) to examine how contingent cannabis use and cue‐induced cannabinoid‐seeking alters glutamatergic neurotransmission and synaptic plasticity in NAcore. NMDA receptor (NMDAR)–dependent long‐term depression (LTD) in the NAcore was lost after cannabinoid, but not sucrose self‐administration. Surprisingly, when rats underwent cue‐induced cannabinoid seeking, LTD was restored. Loss of LTD was accompanied by desensitization of cannabinoid receptor 1 (CB1R). CB1R are positioned to regulate synaptic plasticity by being expressed on glutamatergic terminals and negatively regulating presynaptic excitability and glutamate release. Supporting this possibility, LTD was restored by promoting CB1R signaling with the CB1 positive allosteric modulator GAT211. These data implicate NAcore CB1R as critical regulators of metaplasticity induced by cannabis self‐administration and the cues predicting cannabis availability.
Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization
Authors: Treur Jorien L. , Demontis Ditte , Smith George Davey , Sallis Hannah , Richardson Tom G. , Wiers Reinout W. , Børglum Anders D. , Verweij Karin J.H. , Munafò Marcus R. 
Published: November 2019

AbstractAttention‐deficit hyperactivity disorder (ADHD) has consistently been associated with substance use, but the nature of this association is not fully understood. To inform intervention development and public health messages, a vital question is whether there are causal pathways from ADHD to substance use and/or vice versa. We applied bidirectional Mendelian randomization, using summary‐level data from the largest available genome‐wide association studies (GWAS) on ADHD, smoking (initiation, cigarettes per day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks per week, alcohol problems, and alcohol dependence), cannabis use (initiation), and coffee consumption (cups per day). Genetic variants robustly associated with the “exposure” were selected as instruments and identified in the “outcome” GWAS. Effect estimates from individual genetic variants were combined with inverse‐variance weighted regression and five sensitivity analyses (weighted median, weighted mode, MR‐Egger, generalized summary data–based MR, and Steiger filtering). We found evidence that liability to ADHD increases likelihood of smoking initiation and heaviness of smoking among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation. There was weak evidence that liability to ADHD increases alcohol dependence risk but not drinks per week or alcohol problems. In the other direction, there was weak evidence that smoking initiation increases ADHD risk, but follow‐up analyses suggested a high probability of horizontal pleiotropy. There was no clear evidence of causal pathways between ADHD and coffee consumption. Our findings corroborate epidemiological evidence, suggesting causal pathways from liability to ADHD to smoking, cannabis use, and, tentatively, alcohol dependence. Further work is needed to explore the exact mechanisms mediating these causal effects.
Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation
Authors: Israel Yedy , Quintanilla María Elena , Ezquer Fernando , Morales Paola , Santapau Daniela , Berríos‐Cárcamo Pablo , Ezquer Marcelo , Olivares Belen , Herrera‐Marschitz Mario 
Published: November 2019

AbstractChronic alcohol intake leads to neuroinflammation and cell injury, proposed to result in alterations that perpetuate alcohol intake and cued relapse. Studies show that brain oxidative stress is consistently associated with alcohol‐induced neuroinflammation, and literature implies that oxidative stress and neuroinflammation perpetuate each other. In line with a self‐perpetuating mechanism, it is hypothesized that inhibition of either oxidative stress or neuroinflammation could reduce chronic alcohol intake and relapse. The present study conducted on alcohol‐preferring rats shows that chronic ethanol intake was inhibited by 50% to 55% by the oral administration of low doses of either the antioxidant N‐acetylcysteine (40 mg/kg/d) or the anti‐inflammatory aspirin (ASA; 15 mg/kg/d), while the co‐administration of both dugs led to a 70% to 75% (P < .001) inhibition of chronic alcohol intake. Following chronic alcohol intake, a prolonged alcohol deprivation, and subsequent alcohol re‐access, relapse drinking resulted in blood alcohol levels of 95 to 100 mg/dL in 60 minutes, which were reduced by 60% by either N‐acetylcysteine or aspirin and by 85% by the co‐administration of both drugs (blood alcohol: 10 to 15 mg/dL; P < .001). Alcohol intake either on the chronic phase or following deprivation and re‐access led to a 50% reduction of cortical glutamate transporter GLT‐1 levels, while aspirin administration fully returned GLT‐1 to normal levels. N‐acetylcysteine administration did not alter GLT‐1 levels, while N‐acetylcysteine may activate the cystine/glutamate transport xCT, presynaptically inhibiting relapse. Overall, the study suggests that a neuroinflammation/oxidative stress self‐perpetuation cycle maintains chronic alcohol intake and relapse drinking. The co‐administration of anti‐inflammatory and antioxidant agents may have translational value in alcohol‐use disorders.
What agricultural and food policies do U.S. consumers prefer? A best–worst scaling approach
Authors: Caputo Vincenzina , Lusk Jayson L. 
Published: November 2019

AbstractConsumer welfare effects from policy changes are traditionally calculated using estimates of consumer preferences for the underlying goods and services affected. This conventional approach is indirect, does not consider preferences people may have for the policies themselves, and makes it difficult to easily compare relative preferability of a large set of policy options. In this paper, we use the best–worst scaling approach to determine consumers’ preferences for 13 policies. A nationwide survey of 1,056 U.S. consumers indicates the highest levels of support for investments in agricultural research and requirements of food and agricultural literacy standards in public education. Fat, calorie, and soda taxes are the least popular; fewer than one‐third of respondents are in favor of these three policies.
Global and local food value chains in Africa: A review
Authors: Feyaerts Hendrik , Van den Broeck Goedele , Maertens Miet 
Published: November 2019

AbstractThe rapid expansion of agrifood exports from low‐ and middle‐income countries and the contribution of global value chains to rural development are well‐documented in the literature. Also, studies on modernization of domestic food value chains in these countries are emerging. Yet, the linkages between global and local value chains are rarely studied. On the one hand, the development and expansion of global value chains may create competition with local value chains for land, labor, water, soil nutrients, and other resources. On the other hand, positive spillover effects, such as investment, technical or institutional spillovers, may occur and spur the development of local value chains. In this article, we put forward a conceptual discussion on the type of linkages between global and local value chains, and how these depend on crop and value chain characteristics. We review the empirical evidence on these linkages. Our focus is on Africa, where agrifood exports and global value chains evolved rapidly and where challenges remain to upgrade and increase efficiency in local food value chains.
Trade, policy, and food security
Authors: Smith Vincent H. , Glauber Joseph W. 
Published: November 2019

AbstractFood insecurity is extensive throughout the world and hunger and malnutrition are expected to remain serious humanitarian and political concerns, both in the short term and for the foreseeable future, particularly in low income developing countries where many rural and urban households are both income and asset poor. In those countries, domestic agricultural production is expected to be especially vulnerable to the impacts of climate change over the next 30 years. Thus international markets for staple agricultural commodities, which have become increasingly important as sources of nutrition for both developing and developed countries over the past 60 years, are likely to become even more important in the future. Free trade policies allow countries to exploit their comparative advantages in economic activity, increasing average per capita incomes, longer term growth rates and a country's capacity to fund social safety nets for the poor. However, many countries abandoned those policies in favor of domestic protections in their efforts to mitigate the effects of short run food crises. The policy challenge is therefore to resolve the tension between optimal long run policies and short run initiatives to address food security concerns.
Prevalence of non‐alcoholic fatty liver and liver fibrosis in patients with moderate–severe psoriasis: A cross‐sectional cohort study
Authors: Magdaleno‐Tapial Jorge , Valenzuela‐Oñate Cristian , Ortiz‐Salvador José María , Martínez‐Doménech Álvaro , García‐Legaz‐Martínez Marta , Alonso‐Carpio Miriam , Tamarit‐García Juan José , Diago‐Madrid Moisés , Sánchez‐Carazo José Luis , Pérez‐Ferriols Amparo 
Published: November 2019

AbstractBackground/ObjectivesSeveral studies have reported that non‐alcoholic fatty liver disease (NAFLD) is more frequent in patients with psoriasis, but few have reviewed the presence of liver fibrosis in those patients.MethodsCross‐sectional cohort, single‐centre study, continuously selecting all patients with moderate–severe psoriasis seen at the Psoriasis Unit of a Tertiary Hospital. The grade of liver steatosis was assessed using liver ultrasound, and the quantity of liver fibrosis was graded using a transitional vibration‐controlled elastography (Fibroscan®).ResultsA total of 71 patients (66.2% male) were included, with an average age of 46.6 years old. The maximum historical PASI average was 14.4 while the baseline PASI average at the time of the study was 2. A third (36%) of patients met the criteria for metabolic syndrome 52% of patients had steatosis; being male, having metabolic syndrome comorbidities, elevated AST/ALT enzymes, dyslipidemia and high initial PASI were significantly related. 14% of patients had moderate liver fibrosis (≥7.6 KPa). In 30% of them, no ultrasound liver steatosis was observed.ConclusionsElastography may be a useful tool along with ultrasound to evaluate liver disease in patients with psoriasis.