bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosynthesis of cofactor‐activatable iron‐only nitrogenase in Saccharomyces cerevisiae
Authors: López‐Torrejón Gema , Burén Stefan , Veldhuizen Marcel , Rubio Luis M. 
Published: January 2021

SummaryEngineering nitrogenase in eukaryotes is hampered by its genetic complexity and by the oxygen sensitivity of its protein components. Of the three types of nitrogenases, the Fe‐only nitrogenase is considered the simplest one because its function depends on fewer gene products than the homologous and more complex Mo and V nitrogenases. Here, we show the expression of stable Fe‐only nitrogenase component proteins in the low‐oxygen mitochondria matrix of S. cerevisiae. As‐isolated Fe protein (AnfH) was active in electron donation to NifDK to reduce acetylene into ethylene. Ancillary proteins NifU, NifS and NifM were not required for Fe protein function. The FeFe protein existed as apo‐AnfDK complex with the AnfG subunit either loosely bound or completely unable to interact with it. Apo‐AnfDK could be activated for acetylene reduction by the simple addition of FeMo‐co in vitro, indicating preexistence of the P‐clusters even in the absence of coexpressed NifU and NifS. This work reinforces the use of Fe‐only nitrogenase as simple model to engineer nitrogen fixation in yeast and plant mitochondria.
Lactic acid bacteria as probiotics for the nose?
Authors: De Boeck Ilke , Spacova Irina , Vanderveken Olivier M. , Lebeer Sarah 
Published: January 2021

SummarySeveral studies have recently pointed towards an increased occurrence and prevalence of several taxa of the lactic acid bacteria (LAB) in the microbiota of the upper respiratory tract (URT) under healthy conditions versus disease. These include several species of the Lactobacillales such as Lacticaseibacillus casei, Lactococcus lactis and Dolosigranulum pigrum. In addition to physiological studies on their potential beneficial functions and their long history of safe use as probiotics in other human body sites, LAB are thus increasingly to be explored as alternative or complementary treatment for URT diseases. This review highlights the importance of lactic acid bacteria in the respiratory tract and their potential as topical probiotics for this body site. We focus on the potential probiotic properties and adaptation factors that are needed for a bacterial strain to optimally exert its beneficial activity in the respiratory tract. Furthermore, we discuss a range of in silico, in vitro and in vivo models needed to obtain better insights into the efficacy and adaptation factors specifically for URT probiotics. Such knowledge will facilitate optimal strain selection in order to conduct rigorous clinical studies with the most suitable probiotic strains. Despite convincing evidence from microbiome association and in vitro studies, the clinical evidence for oral or topical probiotics for common URT diseases such as chronic rhinosinusitis (CRS) needs further substantiation.
Preoperative predictors of restoration in quality of life after surgery for lung cancer
Authors: Ichimura Hideo , Kobayashi Keisuke , Gosho Masahiko , Nakaoka Kojiro , Yanagihara Takahiro , Ueda Sho , Saeki Yusuke , Maki Naoki , Kobayashi Naohiro , Kikuchi Shinji , Suzuki Hisashi , Goto Yukinobu , Sato Yukio 
Published: January 2021

AbstractBackgroundThe preoperative predictors of quality of life (QOL) in patients who undergo lung resection for lung cancer are poorly known. Here, we investigated these predictors in such patients using two QOL measures.MethodsIn this single‐institutional prospective cohort study, we administered the EQ‐5D‐5 levels (EQ‐5D‐5L) from January 2015, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire with 30 items from April 2015 to April 2018 preoperatively (Pre) and at one month postoperatively (M1), and one year postoperatively (Y1). General health status was measured by the EQ‐5D visual analogue scale (VAS) and EORTC global health status/QOL (GHS) scores. Multivariable linear regression analyses were used to explore the preoperative predictors of QOL at Y1.ResultsA total of 223 patients were included in the study. The EQ‐5D VAS and EORTC GHS scores, at Pre, M1, and Y1, were 80 ± 15, 77 ± 15, and 84 ± 11; and 74 ± 19, 65 ± 20, and 78 ± 17, respectively. In the multivariable analyses, the albumin level, preoperative VAS score, and preoperative pain/discomfort and anxiety/depression were identified as predictors by the EQ‐5D VAS score. The preoperative EORTC GHS score, absence of diabetes mellitus, preoperative cognitive function score, and preoperative symptom score of pain were identified as predictors by the EORTC GHS score.ConclusionsThe EQ‐5D VAS and EORTC GHS scores traced similar trajectories of QOL. In both QOL measures, preoperative pain was found as a common predictor. These predictors may help improve patient/survivor care in the future.
A workflow for accurate metabarcoding using nanopore MinION sequencing
Authors: Baloğlu Bilgenur , Chen Zhewei , Elbrecht Vasco , Braukmann Thomas , MacDonald Shanna , Steinke Dirk 
Published: January 2021

Abstract

Metabarcoding has become a common approach to the rapid identification of the species composition in a mixed sample. The majority of studies use established short‐read high‐throughput sequencing platforms. The Oxford Nanopore MinIONTM, a portable sequencing platform, represents a low‐cost alternative allowing researchers to generate sequence data in the field. However, a major drawback is the high raw read error rate that can range from 10% to 22%.

To test whether the MinIONTM represents a viable alternative to other sequencing platforms, we used rolling circle amplification (RCA) to generate full‐length consensus DNA barcodes for a bulk mock sample of 50 aquatic invertebrate species with at least 15% genetic distance to each other. By applying two different laboratory protocols, we generated two MinIONTM runs that were used to build error‐corrected consensus sequences. A newly developed Python pipeline, ASHURE, was used for data processing, consensus building, clustering and taxonomic assignment of the resulting reads.

Our pipeline achieved median accuracies of up to 99.3% for long concatemeric reads (>45 barcodes) and successfully identified all 50 species in the mock community. The use of RCA was integral for increasing consensus accuracy but was also the most time‐consuming step of the laboratory workflow. Most concatemeric reads were skewed towards a shorter read length range with a median read length of up to 1,262 bp.

Our study demonstrates that Nanopore sequencing can be used for metabarcoding, but exploration of other isothermal amplification procedures to improve consensus accuracy is recommended.
Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans
Authors: Sebastiani Paola , Federico Anthony , Morris Melody , Gurinovich Anastasia , Tanaka Toshiko , Chandler Kevin B. , Andersen Stacy L. , Denis Gerald , Costello Catherine E. , Ferrucci Luigi , Jennings Lori , Glass David J. , Monti Stefano , Perls Thomas T. 
Published: January 2021

AbstractUsing samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age‐matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR < 1%), and two different protein signatures that predict longer survival in centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence‐associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co‐expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
Topical pain control for corneal abrasions: A systematic review and meta‐analysis
Authors: Yu Caberry W. , Kirubarajan Abirami , Yau Matthew , Armstrong Dawn , Johnson Davin E. 
Published: January 2021

AbstractObjectivesCorneal abrasions are common ophthalmic presentations to emergency departments. Among emergency physicians and ophthalmologists, there are highly variable practice patterns with regard to management of resultant pain and discomfort. The goal of this study was to review and analyze the efficacy and safety of topical pain therapies for corneal abrasions, including topical anesthetics, nonsteroidal anti‐inflammatory drugs (NSAIDs), cycloplegics, steroids, pressure patching, and the use of a bandage contact lens (BCL).MethodsThe review followed the Preferred Reporting Items for Systematic Review and Meta‐analysis (PRISMA) guidelines. The protocol was established a priori and published on PROSPERO (CRD42020201288). MEDLINE, EMBASE, CENTRAL, and Web of Science were searched until December 31, 2020. Primary studies comparing topical pain therapies to another therapy or control were included. Primary outcomes included percentage of corneal abrasions healed at 24, 48, and 72 hours, as well as pain control at 24 and 48 hours. Secondary outcomes included use of oral analgesia and incidence of complications. Risk of bias was assessed using validated tools. Quality of evidence was assessed using the GRADE methodology.ResultsOverall, 33 studies (31 randomized controlled trials [RCTs], two cohort studies) comprising 4,167 patients with corneal abrasions were analyzed. Only the data for topical NSAIDs were of adequate evidence from which to draw conclusions; topical NSAIDs demonstrated significantly reduced pain scores at 24 hours (standardized mean differences [SMD] –0.69, 95% CI = –0.98 to –0.41) and 48 hours (SMD = –0.56, 95% CI = –1.02 to –0.10) as well as 53% (95% CI = 34% to 67%) lower oral analgesia use compared to control. Based on available data, topical anesthetics, cycloplegics, patching, and the use of a BCL did not result in any significant difference in pain scores or use of oral analgesia, while no studies examined topical steroids. No interventions resulted in healing delays or significantly higher rates of complications compared to controls.ConclusionsThere was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.
Delineating Developmental Periods in Adulthood Suggests Age‐Related Shifts in the Correlates of Alcohol Use and Problems
Authors: Ellingson Jarrod M. , Littlefield Andrew K. , Wood Phillip K. , Sher Kenneth J. 
Published: January 2021

BackgroundDevelopmental context is related to the propensity to engage in alcohol use, the rate at which alcohol use changes, and the relevance of different risk factors to alcohol use disorder (AUD). Therefore, studies of change should consider developmental nuances, but change is often modeled to follow a uniform pattern, even across distinct developmental periods.MethodsThis study implemented a novel analytic approach to delineate developmental periods of alcohol behavior (n = 478, ages 18 to 35). This approach was further leveraged to examine age‐related shifts in the association of impulsivity risk factors (lack of planning, general sensation seeking, alcohol enhancement expectancies) with alcohol behavior (alcohol quantity*frequency, heavy drinking, AUD).ResultsA sequence of exploratory and confirmatory latent growth models (LGMs) suggested modeling separate linear change factors for alcohol behavior during the primary college (ages 18 to 21) and postcollege years (21 to 35). Bivariate LGMs estimated correlations for alcohol behavior changes with lack of planning, sensation seeking, and enhancement expectancies during these periods. The rate at which heavy drinking changed during the college years was positively correlated with general sensation seeking and lack of planning during this period (rs = 0.61 to 0.63). These correlations were significantly weaker during the postcollege years (rs = 0.29 to 0.34). Notably, the rate of change in alcohol behavior was strongly correlated with enhancement expectancies during the college (r = 0.45 to 0.70) and postcollege years (r = 0.45 to 0.61).ConclusionsThese findings highlight the importance of sensation seeking and lack of planning with regard to adult alcohol use, particularly in a college environment. There was also a strong link between the rates of change in alcohol behavior and enhancement expectancies across all waves. This study supports the utility of exploratory LGMs for delineating developmental periods of alcohol behavior, which are characterized by different processes.
Sex difference in the vulnerability to hippocampus plasticity impairment after binge‐like ethanol exposure in adolescent rat: Is estrogen the key?
Authors: Rabiant Kevin , Antol Johan , Naassila Mickael , Pierrefiche Olivier 
Published: January 2021

AbstractBinge drinking during adolescence induces memory impairments, and evidences suggest that females are more vulnerable than males. However, the reason for such a difference is unclear, whereas preclinical studies addressing this question are lacking. Here we tested the hypothesis that endogenous estrogen level (E2) may explain sex differences in the effects of ethanol on hippocampus plasticity, the cellular mechanism of memory. Long‐term depression (LTD) in hippocampus slice of pubertal female rats was recorded 24 h after two ethanol binges (3 g/kg, i.p., 9 h apart). Neither the estrous cycle nor ethanol altered LTD. However, if ethanol was administered during proestrus (i.e., at endogenous E2 peak), LTD was abolished 24 h later, whereas NMDA‐fEPSPs response to a GluN2B antagonist increased. The abolition of LTD was not observed in adult female rats. Exogenous E2 combined with ethanol replicated LTD abolition in pubertal, prepubertal female, and in pubertal male rats without changes in ethanol metabolism. In male rats, a higher dose of ethanol was required to abolish LTD at 24‐h delay. In pubertal female rats, tamoxifen, an antagonist of estrogen receptors, blocked the impairing effects of endogenous and exogenous E2 on LTD, suggesting estrogen interacts with ethanol through changes in gene expression. In addition, tamoxifen prevented LTD abolition at 24 h but not at 48‐h delay. In conclusion, estrogen may explain the increased vulnerability to ethanol‐induced plasticity impairment seen in females compared with males. This increased vulnerability of female rats is likely due to changes in the GluN2B subunit that represent a common target between ethanol and estrogen.
Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking
Authors: De Falco Emanuela , White Shelby M. , Morningstar Mitchell D. , Ma Baofeng , Nkurunziza Lionnel T. , Ahmed‐Dilibe Anisah , Wellman Cara L. , Lapish Christopher C. 
Published: January 2021

AbstractAlcohol use disorder (AUD) is characterized by impairments in decision‐making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision‐making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre‐existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set‐shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision‐making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables—in this case, impaired cognitive flexibility and heightened urgency, respectively—may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.
Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group
Authors: Cao Zhipeng , Ottino‐Gonzalez Jonatan , Cupertino Renata B. , Schwab Nathan , Hoke Colin , Catherine Orr , Cousijn Janna , Dagher Alain , Foxe John J. , Goudriaan Anna E. , Hester Robert , Hutchison Kent , Li Chiang‐Shan R. , London Edythe D. , Lorenzetti Valentina , Luijten Maartje , Martin‐Santos Rocio , Momenan Reza , Paulus Martin P. , Schmaal Lianne , Sinha Rajita , Sjoerds Zsuzsika , Solowij Nadia , Stein Dan J. , Stein Elliot A. , Uhlmann Anne , van Holst Ruth J. , Veltman Dick J. , Wiers Reinout W. , Yücel Murat , Zhang Sheng , Jahanshad Neda , Thompson Paul M. , Conrod Patricia , Mackey Scott , Garavan Hugh 
Published: January 2021

AbstractBrain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega‐analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance‐general and substance‐specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.
Chronic opipramol treatment extinguishes cocaine craving through Rac1 in responders: A rat model study
Authors: Bareli Tzofnat , Ahdoot Hadas Levi , Ben‐Moshe Hila , Barnea Royi , Warhaftig Gal , Maayan Rachel , Roska Paola , Weizman Abraham , Yadid Gal 
Published: January 2021

AbstractRas‐related C3 botulinum toxin substrate 1 (Rac1), of the Rho small GTPase family, is a key regulator of actin cytoskeleton rearrangement and plays an important role in dendritic morphogenesis. Cocaine produces neuronal alterations, including structural changes in dendritic number and morphology. Emerging data indicate sigma‐1 receptors (σ‐1Rs) as a promising candidate for the prevention of cocaine craving. Opipramol is a σ‐1R agonist approved in some European countries for depression and anxiety. Here we report that opipramol, mediated by Rac1, attenuates cocaine‐seeking behavior in a rat model of self‐administration. The opipramol effect was shown in two phases. It decreased cocaine‐seeking behavior throughout the withdrawal phase and, interestingly, showed a significant reduction of cocaine‐primed reinstatement in 75% of the opipramol‐treated group (termed ‘responders’). All opipramol‐treated rats showed a decrease in σ‐1R mRNA expression levels in the nucleus accumbens (NAc) versus controls. Responders also exhibited significantly decreased NAc Rac1 mRNA expression levels, compared with non‐responder rats. Hence, Rac1 differentiated responders from non‐responders. Rac1 correlated positively with σ‐1R mRNA levels in opipramol responders. In another experiment, Rac1 inhibitor injected directly into the NAc core decreased active lever presses on the first day of extinction, indicating the critical role of Rac1 in the opipramol effect on drug seeking. We postulate that chronic activation of σ‐1R, through a dynamic interaction with Rac1, may suggest a new approach to treat substance use disorder (SUD). Rac1 inhibition is a prerequisite for decreasing drug seeking and rehabilitation, and this can be achieved by opipramol, a medication that can be given during detoxification.