bluuebunny/crossref_metadata_2025_split huggingface dataset:
Greater resistance to footshock punishment in female C57BL/6J mice responding for ethanol
Authors: Sneddon Elizabeth A. , Fennell Kaila A. , Bhati Sachi , Setters Joshua E. , Schuh Kristen M. , DeMedio Jenelle N. , Arnold Brandon J. , Monroe Sean C. , Quinn Jennifer J. , Radke Anna K. 
Published: August 2022

AbstractBackgroundOne characteristic of alcohol use disorder (AUD) is compulsive drinking, or drinking despite negative consequences. When quinine is used to model such aversion-resistant drinking, female rodents typically are more resistant to punishment than males. Using an operant response task where C57BL/6J responded for ethanol (EtOH) mixed with quinine, we previously demonstrated that female mice tolerate higher concentrations of quinine in EtOH than males. Here, we aimed to determine if this female vulnerability to aversion-resistant drinking behavior is similarly observed when footshock punishment is used.MethodsMale and female C57BL/6J mice were trained to respond for 10% EtOH in an operant task on a fixed ratio 3 schedule. After consistent responding, mice were tested in a punishment session using either a 0.25 mA or 0.35 mA footshock. To assess footshock sensitivity, a subset of mice underwent a flinch, jump, vocalize test in which behavioral responses to increasing amplitudes of footshock (0.05 – 0.95 mA) were assessed. In a separate cohort of mice, males and females were trained to respond for 2.5% sucrose and responses were punished using a 0.25 mA footshock.ResultsMales and females continued to respond for 10% EtOH when paired with a 0.25 mA footshock. Females alone continued to respond for EtOH when a 0.35 mA footshock was delivered. Both males and females reduced responding for 2.5% sucrose when punished with a 0.25 mA footshock. Finally, footshock sensitivity in the flinch, jump, vocalize test did not differ by sex.ConclusionsFemales continue to respond for 10% EtOH despite a 0.35 mA footshock and this behavior is not due to differences in footshock sensitivity between males and females. These results suggest that female C57BL/6J mice are generally more resistant to punishment in an operant self-administration paradigm. These results add to the literature characterizing aversion-resistant alcohol drinking behaviors in females.
Drosophila Tropomodulin is required for multiple actin-dependent processes in myofiber assembly and maintenance
Authors: Zapater i Morales Carolina , Carman Peter J. , Soffar David B. , Windner Stefanie E. , Dominguez Roberto , Baylies Mary K. 
Published: August 2022

ABSTRACTProper muscle contraction requires the assembly and maintenance of sarcomeres and myofibrils. While the protein components of myofibrils are generally known, less is known about the mechanisms by which they individually function and together synergize for myofibril assembly and maintenance. For example, it is unclear how the disruption of actin filament (F-actin) regulatory proteins leads to the muscle weakness observed in myopathies. Here, we show that knockdown of Drosophila Tropomodulin (Tmod) results in several myopathy-related phenotypes, including reduction of muscle cell (myofiber) size, increased sarcomere length, disorganization and misorientation of myofibrils, ectopic F-actin accumulation, loss of tension-mediating proteins at the myotendinous junction, and misshaped and internalized nuclei. Our findings support and extend the tension-driven self-organization myofibrillogenesis model. We show that, like its mammalian counterpart, Drosophila Tmod caps F-actin pointed-ends, and this activity is critical for cellular processes in different locations within the myofiber that directly and indirectly contribute to the maintenance of muscle function. Our findings provide significant insights to the role of Tmod in muscle development, maintenance, and disease.SUMMARY STATEMENTDrosophila Tropomodulin knockdown in larval myofibers results in myopathy-related phenotypes. Our findings support that Tmod acts in actin-related processes at different subcellular locales, all critical for muscle integrity and function.
Psychometric and subcortical neurometric measures of temporal discrimination in rhesus macaques
Authors: Mackey Chase A. , Hauser Samantha , Schoenhaut Adriana M. , Temghare Namrata , Ramachandran Ramnarayan 
Published: August 2022

ABSTRACTTemporal envelope fluctuations are abundant in nature and are critical for perception of complex sounds. While psychophysical sinusoidal amplitude modulation (SAM) processing studies have characterized the perception of SAM, and neurophysiological studies report a subcortical transformation from temporal to rate-based code, no studies have characterized this transformation in unanesthetized animals or in nonhuman primates. To address this, we recorded single-unit responses and compared derived neurometric measures in the cochlear nucleus (CN) and inferior colliculus (IC) to psychometric measures of modulation frequency (MF) discrimination in macaques. IC and CN neurons often exhibited tuned responses to SAM in their rate and spike-timing. Neurometric thresholds spanned a large range (2-200 Hz Δ MF). The lowest 40% of IC thresholds were less than or equal to psychometric thresholds, regardless of which code was used, while CN thresholds were greater than psychometric thresholds. Discrimination at 10-20 Hz could be explained by indiscriminately pooling 30 units in either structure, while discrimination at higher MFs was best explained by more selective pooling. This suggests that pooled brainstem activity was sufficient for AM discrimination. Psychometric and neurometric thresholds decreased as a function of stimulus duration, but IC and CN thresholds were greater and more variable than behavior at durations less than 500 ms. This slower subcortical temporal integration compared to behavior was consistent with a drift diffusion model which reproduced individual differences in performance and can constrain future neurophysiological studies of temporal integration. These measures provide an account of AM perception at the neurophysiological, computational, and behavioral levels.Significance statementListening in everyday environments tasks the brain with extracting information from sound envelopes. This process involves both sensory encoding and decision-making. Different neural codes for envelope representation have been well characterized in the auditory midbrain and cortex, but studies of the brainstem have usually been conducted in anesthetized rodents or cats. Moreover, these candidate neural codes have been studied in isolation from the decision-making process. In this study, we found that population activity in the primate subcortical auditory system contains sufficient information for discriminating sound envelope and applied a biologically plausible model of decision-making to sound envelope discrimination performance from rhesus macaques, a species with great phylogenetic and perceptual similarity to humans.
Multi-areal neural dynamics encode human decision making
Authors: Overton Jacqueline A. , Moxon Karen , Stickle Matthew P. , Peters Logan M. , Lin Jack J. , Chang Edward F. , Knight Robert T. , Hsu Ming , Saez Ignacio 
Published: August 2022

AbstractValue-based decision-making involves multiple cortical and subcortical brain areas, but the distributed nature of neurophysiological activity underlying economic choices in the human brain remains largely unexplored. Here, we use intracranial recordings from neurosurgical patients to show that risky choices are reflected in high frequency activity distributed across multiple prefrontal and subcortical brain regions, whereas reward-related computations are less widely represented and more modular. State space modeling reveals sub-second neural dynamics underlying choices during deliberation and allows high-accuracy trial-by-trial decoding of subjects’ choices robustly across patients despite differences in anatomical coverage. These results shed light into the neural basis of choice across brain areas and open the door to new intracranial approaches for brain state decoding.
Estimating the genetic parameters of yield-related traits under different nitrogen conditions in maize
Authors: Delen Semra Palali , Xu Gen , Velazquez-Perfecto Jenifer , Yang Jinliang 
Published: August 2022

ABSTRACTUnderstanding the genetic basis responding to nitrogen (N) fertilization in crop production is a long-standing research topic in plant breeding and genetics. Albeit years of continuous efforts, the genetic architecture parameters, such as heritability, polygenicity, and mode of selection, underlying the N responses in maize remain largely unclear. In this study, aboutn= 230 maize inbred lines were phenotyped under high N (HN) and low N (LN) conditions for two consecutive years to obtain six yield-related traits. Heritability analyses suggested that traits highly responsive to N treatments were less heritable. Using publicly available SNP genotypes, the genome-wide association study (GWAS) was conducted to identifyn= 231 andn= 139 trait-associated loci (TALs) under HN and LN conditions, respectively, andn= 162 TALs for N-responsive (NR) traits. Furthermore, genome-wide complex trait Bayesian (GCTB) analysis, a method complementary to GWAS, was performed to estimate genetic parameters, including genetic polygenicity and the mode of selection (S). GCTB results suggested that the NR value of a yield component trait was highly polygenic and that four NR traits exhibited negative correlations between SNP effects and their minor allele frequencies (or theSvalue < 0) — a pattern consistent with negative selection to purge deleterious alleles. This study reveals the complex genetic architecture underlying N responses for yield-related traits and provides insights into the future direction for N resilient maize development.
Intracytoplasmic membranes develop inGeobacter sulfurreducensunder thermodynamically limiting conditions
Authors: Howley Ethan , Mangus Anna , Williams Dewight , Torres César I. 
Published: August 2022

AbstractGeobacter sulfurreducensis an electroactive bacterium capable of reducing metal oxides in the environment and electrodes in engineered systems1,2.Geobacter sp. are the keystone organisms in electrogenic biofilms, as their respiration consumes fermentation products produced by other organisms and reduces a terminal electron acceptor e.g. iron oxide or an electrode. To respire extracellular electron acceptors with a wide range of redox potentials,G. sulfurreducenshas a complex network of respiratory proteins, many of which are membrane-bound3–5. We have identified intracytoplasmic membrane (ICM) structures inG. sulfurreducens. This ICM is an invagination of the inner membrane that has folded and organized by an unknown mechanism, often but not always located near the tip of a cell. Using confocal microscopy, we can identify that at least half of the cells contain an ICM when grown on low potential anode surfaces, whereas cells grown at higher potential anode surfaces or using fumarate as electron acceptor had significantly lower ICM frequency. 3D models developed from cryo-electron tomograms show the ICM to be a continuous extension of the inner membrane in contact with the cytoplasmic and periplasmic space. The differential abundance of ICM in cells grown under different thermodynamic conditions supports the hypothesis that it is an adaptation to limited energy availability, as an increase in membrane-bound respiratory proteins could increase electron flux. Thus, the ICM provides extra inner-membrane surface to increase the abundance of these proteins.G. sulfurreducensis the first Thermodesulfobacterium or metal-oxide reducer found to produce ICMs.
Rates but not acoustic features of ultrasonic vocalizations are related to non-vocal behaviors in mouse pups
Authors: Pranic Nicole M. , Kornbrek Caroline , Yang Chen , Cleland Thomas A. , Tschida Katherine A. 
Published: August 2022

AbstractMouse pups produce ultrasonic vocalizations (USVs) in response to isolation from the nest (i.e., isolation USVs). Rates and acoustic features of isolation USVs change dramatically over the first two weeks of life, and there is also substantial variability in the rates and acoustic features of isolation USVs at a given postnatal age. The factors that contribute to within-age variability in isolation USVs remain largely unknown. Here, we explore the extent to which non-vocal behaviors of mouse pups relate to the within-age variability in rates and acoustic features of their USVs. We recorded non-vocal behaviors of isolated C57BL/6J mouse pups at four postnatal ages (postnatal days 5, 10, 15, and 20), measured rates of isolation USV production, and applied a combination of hand-picked acoustic feature measurements and an unsupervised machine learning-based vocal analysis method to examine USV acoustic features. When we considered different categories of non-vocal behavior, our analyses revealed that mice in all postnatal age groups produce higher rates of isolation USVs during active non-vocal behaviors than when lying still. Moreover, rates of isolation USVs are correlated with the intensity (i.e., magnitude) of non-vocal body and limb movements within a given trial. In contrast, USVs produced during different categories of non-vocal behaviors and during different intensities of non-vocal movement do not differ substantially in their acoustic features. Our findings suggest that levels of behavioral arousal contribute to within-age variability in rates, but not acoustic features, of mouse isolation USVs.
Compost Teas: market survey and microbial analysis
Authors: Legein Marie , Van Beeck Wannes , Muyshondt Babette , Wuyts Karen , Samson Roeland , Lebeer Sarah 
Published: August 2022

AbstractCompost teas (CTs) are fermented watery compost extracts that can be made with a wide variety of organic ingredients. These extracts are applied on plants to promote plant growth and increase protection against pathogens. Several studies have shown that the live micro-organisms present in these teas play an important role in plant protection. Still, our knowledge on the identity and functionality of bacterial communities in CTs remains limited. Moreover, CTs are a heterogeneous group, as various combinations of ingredients, fermentation parameters and application guidelines are possible and little is known on the current practices in commercially available products. Consequently, also the microbial communities in these commercially available CTs are unknown. Here, we surveyed 68 CTs on ingredients, claims and guidelines regarding preparation and application. This revealed that most products were sold in dried form which needed to be rehydrated by the customers. Moreover, kelp, humic acid, sugar and molasses, were common ingredients. Additionally, we investigated the bacterial communities of eight products, covering different ingredients and preparations, using sequencing and culture-based techniques. Bacterial communities were remarkably similar at genus level, with Pseudomonas, Massilia, Comamonas, Chryseobacterium, Brevundimonas and Acinetobacter as most prevalent genera. The genus Pseudomonas was more abundant in CTs that were prepared without aeration. Moreover, differences between liquid and dry products revealed the importance of formulation to secure the viability of the desired microbes. This study has given insight in common practices in CTs on the market, their microbial composition, and highlighted several discrepancies with current literature.ImportanceCompost teas are fermented watery compost extracts which are used in professional and amateur horticulture to promote plant growth and suppress plant diseases. Beneficial microbes present in these extracts are suggested to play an important role in the mode of action. However, little is known on the identity and functionality of the bacteria in compost teas. Moreover, compost teas are a heterogeneous group of products that can be made with numerous combinations of ingredient and fermentation parameters and little is known on current practices in products available on the market. Therefore, we surveyed these practices in 68 commercial products and for a subset of these, we explored their bacterial communities using both culture dependent and independent techniques. This study has unveiled the common practices on the market, their microbial communities, and highlighted several discrepancies between commercial practices and scientific research.
Simulated colonic fluid replicates the in vivo growth capabilities of Citrobacter rodentium cpxRA mutants and uncovers additive effects of Cpx regulated genes on fitness
Authors: Gilliland Ashley , Gavino Christina , Gruenheid Samantha , Raivio Tracy 
Published: August 2022

AbstractCitrobacter rodentium is an attaching and effacing (A/E) pathogen used to model enteropathogenic and enterohemorrhagic Escherichia coli infections in mice. During colonization, C. rodentium must adapt to stresses in the gastrointestinal tract such as antimicrobial peptides, pH changes, and bile salts. The Cpx envelope stress response (ESR) is a two-component system used by some bacteria to remediate stress by modulating gene expression and is necessary for C. rodentium pathogenesis in mice. Here, we utilized simulated colonic fluid (SCF) to mimic the gastrointestinal environment which we show strongly induces the Cpx ESR and highlights a fitness defect specific to the ΔcpxRA mutant. While investigating genes in the Cpx regulon that may contribute to C. rodentium pathogenesis, we found that the absence of the Cpx ESR resulted in higher expression of the LEE master regulator, ler, and the genes yebE, ygiB, bssR, and htpX relied on CpxRA for proper expression. We then determined that CpxRA and select gene mutants were essential for proper growth in SCF when in the presence of extraneous stressors and in competition. Although none of the Cpx-regulated gene mutants exhibited marked virulence phenotypes in vivo, the ΔcpxRA mutant had reduced colonization and attenuated virulence, as previously determined, which replicated the in vitro growth phenotypes specific to SCF. Overall, these results indicate that the ΔcpxRA virulence defect is not due to any single Cpx regulon gene examined. Instead, attenuation may be the result of defective growth in the colonic environment resulting from the collective impact of multiple Cpx-regulated genes.
Genetically-proxied impaired GIPR signalling and risk of 6 cancers
Authors: Rogers Miranda , Gill Dipender , Ahlqvist Emma , Robinson Tim , Mariosa Daniela , Johansson Mattias , Penha Ricardo Cortez Cardoso , Dossus Laure , Gunter Marc J , Moreno Victor , Davey Smith George , Martin Richard M , Yarmolinsky James 
Published: August 2022

AbstractBackgroundPreclinical and human genetics studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling worsens glycaemic control. The relationship between GIPR signalling and risk of cancers influenced by impaired glucose homeostasis is unclear.MethodsWe examined the association of a missense variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signalling and lower circulating GIP concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis. Summary genetic association data on breast, colorectal, endometrial, lung, pancreatic, and renal cancer risk were obtained from GWAS consortia (235,698 cases, 333,932 controls). Replication analyses were performed in the FinnGen consortium (8,401 breast cancer cases, 99,321 controls). Colocalisation was performed to examine robustness of findings to genetic confounding. Finally, we examined the association of E354Q with potential downstream molecular mediators of GIPR signalling to identify possible mechanisms underpinning an effect on cancer risk.ResultsEach copy of E354Q was associated with a higher risk of overall breast cancer (OR:1.05,95%CI:1.03-1.06,P=4.23×10−9) and luminal A-like breast cancer (OR:1.05,95%CI:1.03-1.06,P=6.02×10−7). In replication analysis, E354Q was likewise associated with breast cancer risk (OR:1.06,95%CI:1.02-1.08,P=1.09×10−3) and in colocalisation there was a >99.9% posterior probability of circulating GIP concentrations sharing a causal variant with overall and luminal A-like breast cancer in GIPR. E354Q was not associated with risk of the 5 other cancers examined. In mechanistic analysis, this variant was associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations.ConclusionOur comprehensive drug target-Mendelian randomization analysis across 6 cancers suggests an adverse effect of the GIPR E354Q variant on overall and luminal A-like breast cancer risk. These findings provide genetic evidence to support further evaluation of the therapeutic potential of GIPR signalling in breast cancer prevention.
The tryptophan catabolite or kynurenine pathway in a major depressive episode with melancholia, psychotic features and suicidal behaviors; a systematic review and meta-analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Vasupanrajit Asara , Tunvirachaisakul Chavit , Oxenkrug Gregory , Al-Hakeim Hussein K. , Maes Michael 
Published: August 2022

AbstractBackgroundMajor depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory and oxidative pathways which may stimulate indoleamine 2,3- dioxygenase (IDO), the first and rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway resulting in increased tryptophan degradation and elevated tryptophan catabolites (TRYCTAs).ObjectiveThe purpose of the current study is to systematically review and meta-analyze levels of TRP, its competing amino-acids (CAAs) and TRYCATs in patients with severe affective disorders.MethodsPubMed, Google Scholar and SciFinder were searched in the present study and we recruited 35 studies to examine 4,647 participants including 2,332 unipolar (MDD) and bipolar (BD) depressed patients and 2,315 healthy controls.ResultsSevere patients showed significant lower (p<0.0001) TRP (standardized mean difference, SMD=-0.517, 95% confidence interval, CI: -0.735; -0.299) and TRP/CAA (SMD= -0.617, CI: -0.957; -0.277) levels with moderate effect sizes, while no significant difference in CAAs were found. Kynurenine (KYN) levels were unaltered in severe MDD/BD phenotypes, while the KYN/TRP ratio showed a significant increase only in patients with psychotic features (SMD= 0.224, CI: 0.012; 0.436). Quinolinic acid (QA) was significantly increased (SMD= 0.358, CI: 0.015; 0.701) and kynurenic acid (KA) significantly decreased (SMD= -0.260, CI: -0.487; -0.034) in severe MDD/BD.ConclusionPatients with affective disorders with melancholic and psychotic features and suicidal behaviors show normal IDO enzyme activity but a lowered availability of plasma/serum TRP to the brain, which is probably due to other processes such as low albumin levels.