bluuebunny/crossref_metadata_2025_split huggingface dataset:
As above, so below: Whole transcriptome profiling supports the continuum hypothesis of avian dorsal and ventral pallium organization
Authors: Gedman Gregory , Haase Bettina , Durieux Gillian , Biegler Matthew , Fedrigo Olivier , Jarvis Erich D. 
Published: November 2020

AbstractOver the last two decades, beginning with the Avian Brain Nomenclature Forum in 2000, major revisions have been made to our understanding of the organization and nomenclature of the avian brain. However, there are still unresolved questions on avian pallial organization, particularly whether the cells above the ventricle represent different populations to those below it. Concerns included limited number of genes profiled, biased selection of genes, and potential independent origins of cell types in different parts of the brain. Here we test two competing hypotheses, using RNA sequencing to profile the transcriptomes of the major avian pallial subdivisions dorsal and ventral to the ventricle boundary, and a new zebra finch genome assembly containing about 22,000 annotated, complete genes. We found that the transcriptomes of neural populations below and above the ventricle were remarkably similar. What had been previously named hyperpallium densocellulare above the ventricle had nearly the same molecular profile as the mesopallium below it; the hyperpallium apicale above was highly similar to the nidopallium below; the primary sensory intercalated hyperpallium apicale above was most similar to the sensory population below, although more divergent than the other populations were to each other. These shared population expression profiles define unique functional specializations in anatomical structure development, synaptic transmission, signaling, and neurogenesis. These findings support the continuum hypothesis of avian brain subdivisions above and below the ventricle space, with the pallium as a whole consisting of four major cell populations instead of seven and has some profound implications for our understanding of vertebrate brain evolution.
Reanalysis of in vivo drug synergy validation study rules out synergy in most cases
Authors: van Tellingen Olaf , de Menezes Renee X. 
Published: November 2020

AbstractIn a recent paper in Nature Communications, Narayan et al1described the development of anin silicomethod to predict synergy of drug combinations, validatedin vivousing 5 different models for 5 different drug pairs. The published analysis of thein vivoexperimental data used the Chou and Talalay Combination Index, which ignores important aspects of the study design, including, but not limited to the variability between individual mice and the longitudinal nature of the data. Furthermore, the original publication reported the Combination Index as static numbers without properly accounting for experimental variability. When 95% confidence intervals are recalculated using bootstrapping methods, 4 out of 5 drug pairs do not show a statistically significant synergistic effect. Three models (originally figures 5A, B and E) are subject to severe inaccuracies in the data handling and reporting. In one model, (originally figure 5D), the data better supports an additive effect between drugs rather than synergy. As the Chou and Talalay Combination Index is poorly suited to this data, we applied mixed-effects models fitted to the longitudinal tumor growth data as an alternative means of estimating synergy. The results support the findings from the bootstrapping analysis, namely that the majority of the drug pairs do not achieve a synergistic effect. We conclude that thein vivovalidation of thein silicomethod to predict synergy of drug combinations as proposed by Narayan et al has a negative outcome when analyzed with appropriate statistical methods.
Sex-specific lipid profiles in the muscle of Atlantic salmon juveniles
Authors: House Andrew H. , Debes Paul V. , Kurko Johanna , Erkinaro Jaakko , Käkelä Reijo , Primmer Craig R. 
Published: November 2020

AbstractEnergy allocation in juvenile fish can have important implications for future life-history progression. Inherited and environmental factors determine when and where individuals allocate energy, and timely and sufficient energy reserves are crucial for reaching key life stages involved in the timing of maturation and sea migration. In Atlantic salmon, lipid reserves are predominantly found in the viscera and myosepta in the muscle and have been shown to play a key role in determining the timing of maturity. This life-history trait is tightly linked to fitness in many species and can be different between males and females, however, the details of relative energy allocation in juveniles of different sexes is not well understood. Therefore, the aim of this study was to investigate the effects of sex, genetics and environment during juvenile development of salmon on the amount and composition of their lipid reserves. To do so, juvenile salmon were fed one of two different lipid food contents during their first summer and autumn under common-garden conditions. Muscle lipid composition and concentrations were determined by thin layer chromatography. The muscle lipid class concentrations covaried negatively with body length and males showed higher concentrations than females for phosphatidylcholine, cholesterol, sphingomyelin, and triacylglycerol. This sex-specific difference in major lipid classes presents a new scope for understanding the regulation of lipids during juvenile development and gives direction for understanding how lipids may interact and influence major life-history traits in Atlantic salmon.
O mouse, where art thou? The Mouse Position Surveillance System (MoPSS) - an RFID based tracking system
Authors: Habedank Anne , Urmersbach Birk , Kahnau Pia , Lewejohann Lars 
Published: November 2020

AbstractExisting methods for analysis of home cage based preference tests are either time consuming, not suitable for group management, expensive and/or based on proprietary equipment that is not freely available. For this reason, we developed an automated system for group housed mice based on radio frequency identification: the Mouse Position Surveillance System (MoPSS). The system uses an Arduino microcontroller with compatible components, it is affordable and easy to rebuild for every laboratory. The MoPSS was validated using female C57BL/6J mice and manual video comparison. It proved to be accurate even for fast moving mice (up to 100 % accuracy after logical reconstruction), and is already implemented in several studies in our laboratory. Here, we provide the complete construction description as well as the validation data and the results of an example experiment. This tracking system will allow group-based preference testing with individually identified mice to be carried out in a convenient manner, creating the foundation for better housing conditions from the animals’ perspective.
Epidural Electrical Stimulation of the Cervical Dorsal Roots Restores Voluntary Upper Limb Control in Paralyzed Monkeys
Authors: Barra B. , Conti S. , Perich M.G. , Zhuang K. , Schiavone G. , Fallegger F. , Galan K. , James N. D. , Barraud Q. , Delacombaz M. , Kaeser M. , Rouiller E. M. , Milekovic T. , Lacour S. , Bloch J. , Courtine G. , Capogrosso M. 
Published: November 2020

SUMMARYRecovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.
Flexible fitting of PROTAC concentration-response curves with changepoint Gaussian Processes
Authors: Semenova Elizaveta , Guerriero Maria Luisa , Zhang Bairu , Hock Andreas , Hopcroft Philip , Kadamur Ganesh , Afzal Avid M. , Lazic Stanley E. 
Published: November 2020

AbstractA proteolysis targeting chimera (PROTAC) is a new technology that marks proteins for degradation in a highly specific manner. During screening, PROTAC compounds are tested in concentration-response (CR) assays to determine their potency, and parameters such as the half-maximal degradation concentration (DC50) are estimated from the fitted CR curves. These parameters are used to rank compounds, with lower DC50values indicating greater potency. However, PROTAC data often exhibit bi-phasic and poly-phasic relationships, making standard sigmoidal CR models inappropriate. A common solution includes manual omitting of points (the so called “masking” step) allowing standard models to be used on the reduced datasets. Due to its manual and subjective nature, masking becomes a costly and non-reproducible procedure. We, therefore, used a Bayesian changepoint Gaussian Processes model that can flexibly fit both non-sigmoidal and sigmoidal CR curves without user input. Parameters, such as the DC50, the maximum effectDmax, and the point of departure (PoD) are estimated from the fitted curves. We then rank compounds based on one or more parameters, and propagate the parameter uncertainty into the rankings, enabling us to confidently state if one compound is better than another. Hence, we used a flexible and automated procedure for PROTAC screening experiments. By minimizing subjective decisions, our approach reduces time, cost, and ensures reproducibility of the compound ranking procedure. The code and data are provided on GitHub (https://github.com/elizavetase-menova/gp_concentration_response).
HIV-1 uncoating by release of viral cDNA from capsid-like structures in the nucleus of infected cells
Authors: Müller Thorsten G. , Zila Vojtech , Peters Kyra , Schifferdecker Sandra , Stanic Mia , Lucic Bojana , Laketa Vibor , Lusic Marina , Müller Barbara , Kräusslich Hans-Georg 
Published: November 2020

AbstractHIV-1 replication commences inside the cone-shaped viral capsid, but timing, localization and mechanism of uncoating are under debate. We adapted a strategy to visualize individual reverse-transcribed HIV-1 cDNA molecules and their association with viral and cellular proteins using fluorescence and correlative-light-and-electron-microscopy (CLEM). We specifically detected HIV-1 cDNA inside nuclei, but not in the cytoplasm. Nuclear cDNA initially co-localized with a fluorescent integrase fusion (IN-FP) and the viral CA (capsid) protein, but cDNA-punctae separated from IN-FP/CA over time. This phenotype was conserved in primary HIV-1 target cells, with nuclear HIV-1 complexes exhibiting strong CA-signals in all cell types. CLEM revealed cone-shaped HIV-1 capsid-like structures and apparently broken capsid-remnants at the position of IN-FP signals and elongated chromatin-like structures in the position of viral cDNA punctae lacking IN-FP. Our data argue for nuclear uncoating by physical disruption rather than cooperative disassembly of the CA-lattice, followed by physical separation from the pre-integration complex.
Community composition of microbial microcosms follows simple assembly rules at evolutionary timescales
Authors: Meroz Nittay , Tovi Nesli , Sorokin Yael , Friedman Jonathan 
Published: November 2020

AbstractManaging and engineering microbial communities relies on the ability to predict their composition. While progress has been made on predicting compositions on short, ecological timescales, there is still little work aimed at predicting compositions on evolutionary timescales. Therefore, it is still unknown for how long communities typically remain stable after reaching ecological equilibrium, and how repeatable and predictable are changes when they occur. Here, we address this knowledge gap by tracking the composition of 87 two- and three-species bacterial communities for ~400 generations. We find that community composition typically changed during evolution, but that the composition of replicate communities remained similar. Furthermore, these changes were predictable in a bottom-up approach - changes in the composition of trios were consistent with those that occurred in pairs during coevolution. Our results demonstrate that simple assembly rules can hold even on evolutionary timescales, suggesting it may be possible to forecast the evolution of microbial communities.
Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress
Authors: Wilkinson Matthew P , Slaney Chloe L , Mellor Jack R , Robinson Emma S J 
Published: November 2020

AbstractEarly life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that similar impairments are present in healthy adults with a history of ELS. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Due to the PRT not meeting its primary endpoint a separate cohort of control participants were tested in a modified PRT where they showed a response bias. This indicates the PRT can be successfully carried out online. Overall, these data suggest that healthy participants without a mental health diagnosis and high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.
The effect of combined treatment of vitamin C and loperamide on intestinal sodium and potassium ion ATPase, alkaline phosphatase and lipid peroxidation on castor oil induced diarrheal rats
Authors: Iorhemba Aondowase Paul , Imolele Anthony Godswill 
Published: November 2020

ABSTRACTBackgroundDiarrhea is distinguished by prevalence of bowel movement accompanied by a loose consistency of stools, resulting from hyper peristalsis of the small intestine or colon, Diarrhea is a major challenge among infants and growing children. The study was carried out to assess the result of combined treatment of vitamin C and loperamide on intestinal Na+, K+- ATPase, alkaline phosphatase, and lipid peroxidation in castor oil induced diarrheal wistar rats.MethodA total of 18 wistar rats weighing 180-200g were randomly divided into 6 groups, (Group 1 Normal control no castor oil, no treatment administered, Group 2 Experimental control were given castor oil 3.0 ml/kg body weight with no treatment, Group 3 Standard control were given castor oil 3.0 ml/kg body weight + loperamide, Group 4 Treatment 1 were administered 3.0 ml/kg body weight + 25 mg/kg combined effect of vitamin C and loperamide, Group 5 Treatment 2 were administered 3.0 ml/kg body weight + 50 mg/kg combined effect of vitamin C and loperamide, and Group 6 were administered 3.0 ml/kg body weight + 100 mg/kg combined effect of vitamin C and loperamide) with 3 rats per group; the experiment lasted for 24 hours. The action of intestinal alkaline phosphatase, Na+, K+- ATPase and malondialdehyde were determined.ResultDescriptive statistical analysis was adopted using SPSS version 20. Combined effect of vitamin C and loperamide significantly (p<0.05) lowered the elevated levels of malondialdehyde caused by castor oil induced diarrhea; the Na+, K+- ATPase intestinal activity treatment with both vitamin C and loperamide significantly elevated the activity of Na+, K+ATPase when compared with the normal control, but both treatments (loperamide alone and vitamin C plus loperamide were not significantly different (p<0.05) to themselves. However, at 50 mg/kg body weight of combined effect of vitamin C and loperamide it showed significant difference in the action of intestinal alkaline phosphatase.ConclusionFindings of this study therefore, indicate that a combined effect of loperamide and vitamin C will be an effective therapeutic agent in the management of diarrhea by scavenging of free radicals generated in the cause of diarrheal to reduce lipid peroxidation. Therefore, combined effect of vitamin C and loperamide should be encouraged in the management of diarrhea. Further research should be directed towards assessing the therapeutic action of vitamin C only in the management of diarrhea.
A model of resource partitioning between foraging bees based on positive and negative associations
Authors: Dubois Thibault , Pasquaretta Cristian , Barron Andrew B. , Gautrais Jacques , Lihoreau Mathieu 
Published: November 2020

AbstractCentral place foraging pollinators tend to develop multi-destination routes (traplines) to visit patchily distributed plant resources. While the formation of traplines by individual pollinators has been studied in details, how populations of foragers exploit resources in a common area is an open question, difficult to address experimentally. We explored conditions for the emergence of resource partitioning among traplining bees using agent-based models built from experimental data of bumblebees foraging on artificial flowers. In the models, bees learn to develop routes as a consequence of feedback loops that change their probabilities of moving between flowers. While a positive reinforcement of movements leading to rewarding flowers is sufficient for the emergence of resource partitioning when flowers are evenly distributed, addition of negative reinforcement of movements leading to unrewarding flowers is necessary when flowers are patchily distributed. In environments with more complex spatial structure, the negative experiences of individual bees on flowers favour spatial segregation and efficient collective foraging.
Profiling ofNUMTs in Gingivobuccal Oral Cancer
Authors: Palodhi Arindam , Singla Tanisha , Maitra Arindam 
Published: November 2020

AbstractVery little information exists on the NUclear MiTochondrial sequences (NUMTs) in oral squamous cell carcinoma-gingivobuccal (OSCC-GB). We analysed whole genome sequences obtained from paired tumour and blood DNA from 25 patients of OSCC-GB for detectingNUMTs. Nine potential somaticNUMTs and 78 germlineNUMTs were identified in these patients. None of the somaticNUMTs could be confirmed by PCR assay. None of the germlineNUMTs were found to be specific for OSCC-GB. Although there have been recent reports on detection of somaticNUMTs in other cancer types, our results suggestNUMTs, both somatic and germline, are not involved in OSCC-GB.
Efficient simultaneous mutagenesis of multiple genes in specific plant tissues by multiplex CRISPR
Authors: Bollier Norbert , Buono Rafael Andrade , Jacobs Thomas B. , Nowack Moritz K. 
Published: November 2020

AbstractMultiplex CRISPR approaches enable mutating multiple genes in plants, however it is unclear how feasible this is in tissue-specific mutagenesis. Here we simultaneously mutated six genes either ubiquitously or exclusively in the root cap of Arabidopsis. The mutation frequencies for all target genes were positively correlated and unaffected by the order of gRNAs in the vector, indicating that efficient higher-order mutagenesis in specific plant tissues can be readily achieved.
Epidermal stem cell compartment remains unaffected through aging in naked mole-rats
Authors: Savina A. , Jaffredo T. , Saldmann F. , Faulkes C.G. , Moguelet P. , Leroy C. , Del Marmol D. , Codogno P. , Foucher L. , Viltard M. , Friedlander G. , Aractingi S. , Fontaine R.H. 
Published: November 2020

ABSTRACTSkin represents an informative and convenient organ for the analysis of the aging process. Naked mole-rats (NMR) are subterranean rodents remarkable for their longevity, with unexplained resistance to skin aging. In middle-aged NMR, extensivein situanalysis indicated that skin compartments and cell types remained similar to young animals. Using single-cell RNA-sequencing, we found three classical cellular states defining a unique keratinocyte differentiation trajectory that did not appear to be altered during aging after pseudotemporal reconstruction. Finally, NMR skin healing closure was strictly comparable between the two age groups. These results indicate that the content in stem cell populations as well as the differentiation process are preserved during aging in NMR and that such properties are related to the healing process.
Substrate-induced modulation of protein-protein interactions within human mitochondrial cytochrome P450-dependent system
Authors: Yablokov E.O. , Sushko T.A. , Kaluzhskiy L.A. , Kavaleuski A.A , Mezentsev Y.V. , Ershov P.V. , Gilep A.A , Ivanov A.S. , Strushkevich N.V. 
Published: November 2020

AbstractSteroidogenesis is strictly regulated at multiple levels, as produced steroid hormones are crucial to maintain physiological functions. Cytochrome P450 enzymes are key players in adrenal steroid hormone biosynthesis and function within short redox-chains in mitochondria and endoplasmic reticulum. However, mechanisms regulating supply of reducing equivalents in the mitochondrial CYP-dependent system are not fully understood. In the present work, we aimed to estimate how the specific steroids, substrates, intermediates and products of multistep reactions modulate protein-protein interactions between adrenodoxin (Adx) and mitochondrial CYP11s. Using the SPR technology we determined that steroid substrates affect affinity and stability of CYP11s – Adx complexes in an isoform-specific mode. In particular, cholesterol induces a 4-fold increase in the rate of CYP11A1 – Adx complex formation without significant effect on dissociation (koffdecreased ~1.5-fold), overall increasing complex affinity. At the same time steroid substrates decrease the affinity of both CYP11B1 – Adx and CYP11B2 – Adx complexes, predominantly reducing their stability (4-7 fold). This finding reveals differentiation of protein-protein interactions within the mitochondrial pool of CYPs, which have the same electron donor. The regulation of electron supply by the substrates might affect the overall steroid hormones production. Our experimental data provide further insight into protein-protein interactions within CYP-dependent redox chains involved in steroidogenesis.