bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of live versus kill pitfall traps to assess the diet of carabids through a metabarcoding approach
Authors: Graux Yohann , Querejeta Marina , Gaba Sabrina , Bretagnolle Vincent , Boyer Stéphane 
Published: March 2023

AbstractMetabarcoding approaches are powerful tools to unravel trophic relationships between predators and prey. To apply metabarcoding analyses on invertebrate gut contents, specimens must be well preserved from DNA degradation, thus the trapping method should be selected accordingly. Dry pitfall traps are commonly assumed to provide a better DNA preservation than traps that use a killing agent. However, this assumption has never been specifically tested for gut content analyses.In our study, we compared how two types of pitfall trapping, dry vs. with brine, affect the conservation of prey DNA contained in the digestive tract of predators and subsequent metabarcoding analyses. We placed dry and “classic” pitfall traps in oilseed rape fields within an intensive agricultural area in the French Nouvelle-Aquitaine region. Traps were set up in autumn and compared for carabid trapping efficiency as well as our capacity to retrieve dietary information from the digestive tract of the main carabid species,Nebria salinaandCalathus fuscipes.PCR success rate was higher in dry pitfall traps compared to classic ones forN. salina. We hypothesise that this was due to the presence of PCR inhibitors in the gut of this species. The ability to sequence prey DNA did not differ between specimens caught in both trap types. The list of predated species was similar between both trap types. However, sequencing yielded more prey OTUs from specimens caught in dry pitfall traps, leading to difference in prey community composition and a greater ability to reconstruct prey communityOur analyses also shed light on the prey spectrum ofCalathus fuscipesandNebria salinain oilseed rape in autumn.
Upregulated GIRK2 counteracts ethanol-induced changes in excitability & respiration in human neurons
Authors: Prytkova Iya , Liu Yiyuan , Fernando Michael , Gameiro-Ros Isabel , Popova Dina , Kamarajan Chella , Xuei Xiaoling , Chorlian David B. , Edenberg Howard J. , Tischfield Jay A. , Porjesz Bernice , Pang Zhiping P. , Hart Ronald P. , Goate Alison , Slesinger Paul A. 
Published: March 2023

ABSTRACTGenome-wide association analysis (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified non-coding polymorphisms within theKCNJ6gene.KCNJ6encodes GIRK2, a subunit of a G protein-coupled inwardly-rectifying potassium channel that regulates neuronal excitability. How changes in GIRK2 affect human neuronal excitability and the response to repeated ethanol exposure is poorly understood. Here, we studied the effect of upregulatingKCNJ6using an isogenic approach with human glutamatergic neurons derived from induced pluripotent stem cells (male and female donors). Using multi-electrode-arrays, population calcium imaging, single-cell patch-clamp electrophysiology, and mitochondrial stress tests, we find that elevated GIRK2 acts in concert with 7-21 days of ethanol exposure to inhibit neuronal activity, to counteract ethanol-induced increases in glutamate response, and to promote an increase intrinsic excitability. Furthermore, elevated GIRK2 prevented ethanol-dependent changes in basal and activity-dependent mitochondrial respiration. These data support a role for GIRK2 in mitigating the effects of ethanol and a previously unknown connection to mitochondrial function in human glutamatergic neurons.SIGNIFICANCE STATEMENTAlcohol use disorder (AUD) is a major health problem that has worsened since COVID, affecting over 100 million people worldwide. While it is known that heritability contributes to AUD, specific genes and their role in neuronal function remain poorly understood, especially in humans. In the current manuscript, we focused on the inwardly-rectifying potassium channel GIRK2, which has been identified in an AUD-endophenotype genome-wide association study. We used human excitatory neurons derived from healthy donors to study the impact of GIRK2 expression. Our results reveal that elevated GIRK2 counteracts ethanol-induced increases in glutamate response and intracellular calcium, as well as deficits in activity-dependent mitochondrial respiration. The role of GIRK2 in mitigating ethanol-induced hyper-glutamatergic and mitochondrial offers therapeutic promise for treating AUD.
Mammalian Esophageal Stratified Tissue Homeostasis is Maintained Distinctively by the Epithelial Pluripotent p63+Sox2+and p63−Sox2+Cell Populations
Authors: Yu Xiaohong , Yuan Hui , Yang Yanan , Zheng Wei , Zheng Xuejing , Lu Shih-Hsin , Jiang Wei , Yu Xiying 
Published: March 2023

AbstractSelf-renewing, damage-repair and differentiation of mammalian stratified squamous epithelia are subject to tissue homeostasis, but the regulation mechanisms remain elusive. Here, we investigate the esophageal squamous epithelial tissue homeostasis in vitro and in vivo. We establish a rat esophageal organoid (rEO) in vitro system and show that the landscapes of rEO formation, development and maturation trajectories can mimic those of rat esophageal epithelia in vivo. Single-cell RNA sequencing (scRNA-seq), snap-shot immunostaining and functional analyses of stratified “matured” rEOs define that the epithelial pluripotent stem-cell determinants, p63 and Sox2, play crucial but distinctive roles for regulating mammalian esophageal tissue homeostasis. We identify two cell populations, p63+Sox2+and p63−Sox2+, of which the p63+Sox2+population presented at the basal layer is the cells of origin required for esophageal epithelial stemness maintenance and proliferation whereas the p63−Sox2+population presented at the suprabasal layers is the cells of origin having a dual role for esophageal epithelial differentiation (differentiation-prone fate) and rapid tissue damage-repair responses (proliferation-prone fate). Given the fact that p63 and Sox2 are developmental lineage oncogenes and commonly overexpressed in ESCC tissues, p63−Sox2+population could not be detected in organoids formed by esophageal squamous cell carcinoma (ESCC) cell lines. Taken together, these findings reveal that the tissue homeostasis is maintained distinctively by p63 and/or Sox2 dependent cell lineage populations required for the tissue renewing, damage-repair and protection of carcinogenesis in mammalian esophagi.
Adaptive therapy for ovarian cancer: An integrated approach to PARP inhibitor scheduling
Authors: Strobl Maximilian , Martin Alexandra L. , West Jeffrey , Gallaher Jill , Robertson-Tessi Mark , Gatenby Robert , Wenham Robert , Maini Philip , Damaghi Mehdi , Anderson Alexander 
Published: March 2023

AbstractToxicity and emerging drug resistance are important challenges in PARP inhibitor (PARPi) treatment of ovarian cancer. Recent research has shown that evolutionary-inspired treatment algorithms which adapt treatment to the tumor’s treatment response (adaptive therapy) can help to mitigate both. Here, we present a first step in developing an adaptive therapy protocol for PARPi treatment by combining mathematical modelling and wet-lab experiments to characterize the cell population dynamics under different PARPi schedules. Using data fromin vitroIncucyte Zoom time-lapse microscopy experiments and a step-wise model selection process we derive a calibrated and validated ordinary differential equation model, which we then use to test different plausible adaptive treatment schedules. Our model can accurately predict thein vitrotreatment dynamics, even to new schedules, and suggests that treatment modifications need to be carefully timed, or one risks losing control over tumour growth, even in the absence of any resistance. This is because our model predicts that multiple rounds of cell division are required for cells to acquire sufficient DNA damage to induce apoptosis. As a result, adaptive therapy algorithms that modulate treatment but never completely withdraw it are predicted to perform better in this setting than strategies based on treatment interruptions. Pilot experimentsin vivoconfirm this conclusion. Overall, this study contributes to a better understanding of the impact of scheduling on treatment outcome for PARPis and showcases some of the challenges involved in developing adaptive therapies for new treatment settings.
An allocentric human odometer for perceiving distances on the ground plane
Authors: Zhou Liu , Wei Wei , Ooi Teng Leng , He Zijiang J. 
Published: March 2023

AbstractWe reliably judge locations of static objects when we walk despite the retinal images of these objects moving with every step we take. Here, we showed our brains solve this optical illusion by adopting an allocentric spatial reference frame. We measured perceived target location after the observer walked a short distance from the home base. Supporting the allocentric coding scheme, we found the intrinsic bias1, 2, which acts as a spatial reference frame for perceiving location of a dimly lit target in the dark, remained grounded at the home base rather than traveled along with the observer. The path-integration mechanism responsible for this can utilize both active and passive (vestibular) translational motion signals, but only along the horizontal direction. This anisotropic path-integration finding in human visual space perception is reminiscent of the anisotropic spatial memory finding in desert ants3, pointing to nature’s wondrous and logically simple design for terrestrial creatures.
Nigral Transcriptomic Profiles in Engrailed-1 Hemizygous Mouse Models of Parkinson’s Disease Reveal Upregulation of Oxidative Phosphorylation-Related Genes Associated with Resistance to Dopaminergic Neurodegeneration
Authors: Belfiori Lautaro , DueñasRey Alfredo , Ralbovszki Dorottya Mária , Jimenez-Ferrer Itzia , Bäckström Filip , Balikai Sagar Shivayogi , Ahrén Dag , Brolin Kajsa , Swanberg Maria 
Published: March 2023

1.AbstractEngrailed 1 (EN1) is a conserved transcription factor essential for programming, survival, and maintenance of midbrain dopaminergic neurons.En1-hemizygosity (En1+/-) leads to a spontaneous Parkinson’s disease-like (PD-like) progressive nigrostriatal degeneration as well as motor impairment and depressive-like behavior in SwissOF1 (OF1-En1+/-) mice. This phenotype is absent in C57Bl/6j (C57-En1+/-) mice. Here we studied PD-like phenotypes and early transcriptome profiles in OF1 wild-type (WT) and OF1-En1+/-male mice and compare to that of C57 WT and C57-En1+/-male mice. To detect transcriptional changes prior to dopaminergic cell loss, we performed RNA-seq of 1-week old mice substantia nigra pars compacta (SNpc). Histology and stereology were used to assess dopaminergic nigrostriatal pathology in 4 and 16 weeks old mice. OF1-En1+/-mice showed an increase (±79%) in dopaminergic striatal axonal swellings from 4 to 16 weeks and a loss (±23%) of dopaminergic neurons in the SNpc at 16 weeks compared to OF1 WT. Axonal swellings were also present in C57-En1+/-mice but did not increase over time. 52 differentially expressed genes (DEGs) were observed between the C57-WT and the C57-En1+/-mice, while 198 DEGs were observed in the OF1 strain. Enrichment analysis revealed that the neuroprotective phenotype of C57-En1+/-mice was associated with an upregulation of oxidative phosphorylation-related genes compared to both C57 WT and to OF1-En1+/-mice.These results highlight the importance of considering genetic background in PD models and provide valuable insight on how expression of mitochondrial proteins before the onset of neurodegeneration is associated to vulnerability of nigrostriatal dopaminergic neurons.2.Significance statementMost PD cases are idiopathic and caused by a complex interplay between genetic variants and environmental risk factors. However, the underlying mechanisms remain elusive. Here we show thatEn1hemizygosity leads to progressive nigrostriatal degeneration with a loss of dopaminergic neurons in OF1-En1+/-but that C57-En1+/-mice only exhibit early signs of nigrostriatal pathology and do not progress to a PD-like phenotype over time. We identified differences in gene expression related to oxidative phosphorylation before the onset of neurodegeneration to be associated to the differential susceptibility toEn1+/-induced PD-like pathology. Our work shows how gene expression changes modulate vulnerability to dopaminergic neurodegeneration in theEn1+/-mouse and reveals putative molecular mechanisms behind the onset and progression of PD.
Estimation of a treatment effect based on a modified covariates method withL0norm
Authors: Tanioka Kensuke , Okuda Kaoru , Hiwa Satoru , Hiroyasu Tomoyuki 
Published: March 2023

AbstractIn randomized clinical trials, we assumed the situation that the new treatment is not adequate compared to the control treatment as result. However, it is unknown if the new treatment is ineffective for all patients or if it is effective for only a subgroup of patients with specific characteristics. If such a subgroup exists and can be detected, the patients can receive effective therapy. To detect subgroups, we need to estimate treatment effects. To achieve this, various treatment effect estimation methods have been proposed based on the sparse regression method. However, these methods are affected by noise. Therefore, we propose new treatment effect estimation approaches based on the modified covariate method, one using lasso regression and the other ridge regression, using theL0norm. The proposed approach was evaluated through numerical simulation and real data examples.
Precision of the Integrated Cognitive Assessment for the assessment of neurocognitive performance in athletes
Authors: Glassbrook Daniel J. , Chazot Paul L. , Hind Karen 
Published: March 2023

AbstractChoice reaction time tests are commonly used for the assessment of cognitive function, and may be useful to assess the effect of sport participation. This study investigated the precision of the Integrated Cognitive Assessment (ICA; Cognetivity Neurosciences Ltd., Vancouver, Canada) test for the assessment of cognitive function in athletes. Thirty-one participants volunteered to take part in this study, from both contact (n= 22) and non-contact sports (n= 9). Participants performed the ICA test consecutively both before and after normal training session to simulate resting and post-sport conditions. Precision errors, relationships (Pearson’s r), and internal consistency (Cronbach’s Alpha) were calculated for three variables, ICA Index (overall information processing ability), ICA Speed (information processing speed) and ICA Accuracy (information processing accuracy). ICA precision errors [root mean squared-standard deviation, RMS-SD (coefficient of variation, %CV)] pre-sport were ICA Index: 5.18 (7.14%), ICA Speed: 3.98 (4.64%), and ICA Accuracy: 3.64 (5.00%); and post-sport were ICA Index: 3.96 (4.94%), ICA Speed: 2.14 (2.32%), and ICA Accuracy 3.40 (4.25%). The ICA test demonstrates high in-vivo precision with all variables except ICA Index (7.14%) demonstrating an acceptable precision error of ≤5% %CV. All variables demonstrated strong relationships between consecutive tests pre- and post-sport (r ≥ 0.8) except for the ICA Index post-sport which demonstrated a moderate (r ≥ 0.5) relationship. The ICA Index demonstrated good internal consistency (α ≥ 0.8) for both pre-and post-sport. The ICA Speed and ICA Accuracy variables demonstrated excellent internal consistency (α ≥ 0.9) for both pre-and post-sport. The ICA test is suitable for the assessment of cognitive function pre- and post-sport.
Basement membrane diversification relies on two competitive secretory routes defined by Rab10 and Rab8 and modulated by dystrophin and the exocyst complex
Authors: Dennis Cynthia , Pouchin Pierre , Richard Graziella , Mirouse Vincent 
Published: March 2023

AbstractThe basement membrane (BM) is an essential structural element of tissues, and its diversification participates in organ morphogenesis. However, the traffic routes associated with BM formation and the mechanistic modulations explaining its diversification are still poorly understood.Drosophila melanogasterfollicular epithelium relies on a BM composed of oriented BM fibrils and a more homogenous matrix. Here, we determined the specific molecular identity and cell exit sites of BM protein secretory routes. First, we found that Rab10 and Rab8 define two parallel routes for BM protein secretion. When both routes were abolished, BM production was fully blocked; however, genetic interactions revealed that these two routes competed. Rab10 promoted lateral and planar-polarized secretion, whereas Rab8 promoted basal secretion, leading to the formation of BM fibrils and homogenous BM, respectively. We also found that the dystrophin-associated protein complex (DAPC) and Rab10 were both present in a planar-polarized tubular compartment containing BM proteins. DAPC was essential for fibril formation and sufficient to reorient secretion towards the Rab10 route. Moreover, we identified a dual function for the exocyst complex in this context. First, the Exo70 subunit directly interacted with dystrophin to limit its planar polarization. Second, the exocyst complex was also required for the Rab8 route. Altogether, these results highlight important mechanistic aspects of BM protein secretion and illustrate how BM diversity can emerge from the spatial control of distinct traffic routes.
Self-loops in Evolutionary Graph Theory: Friends or Foes?
Authors: Sharma Nikhil , Yagoobi Sedigheh , Traulsen Arne 
Published: March 2023

AbstractEvolutionary dynamics in spatially structured populations has been studied for a long time. More recently, the focus has been to construct structures that speeds up evolution – so called amplifiers of selection. It has been shown that for a structure to amplify selection, self-loops are necessary when mutants appear predominately in nodes that change often. As a result, for low mutation rates, self-looped amplifiers attain higher steady-state average fitness in the mutation-selection than well-mixed populations. But, what happens when the mutation rate increases such that fixation probabilities alone no longer describe the dynamics? We show that self-loops effects are detrimental outside the low mutation rate regime. In the intermediate and high mutation rate regime, amplifiers of selection attain lower steady-state average fitness than the complete graph and the suppressor of selection. We also provide an estimate of mutation rate beyond which the mutation-selection dynamics on a graph deviates from the weak mutation rate approximation. This involves computing how the average fixation time scales with the population size for several graphs.
Temporal progression of anaerobic fungal communities in dairy calves from birth to maturity
Authors: Jones Adrienne L. , Clayburn Jordan , Pribil Elizabeth , Foote Andrew P. , Montogomery Dagan , Elshahed Mostafa S. , Youssef Noha H. 
Published: March 2023

AbstractEstablishment of microbial communities in neonatal calves is vital for their growth and overall health. Feed type and associated gastrointestinal tract morphophysiological changes occurring during the pre-weaning, weaning, and post-weaning phases are known to induce shifts in microbial community diversity, structure, and function. However, while the process has received considerable attention for bacteria, our knowledge on temporal progression of anaerobic gut fungi (AGF) in calves is lacking. Here, we examined AGF communities in fecal samples from six dairy cattle collected at 24 different time points during the pre-weaning (day 1-48), weaning (day 49-60), and post-weaning (3-12 months) stages. Quantitative PCR (qPCR) indicated that AGF colonize the calves GIT within 24 hours after birth, with AGF loads slowly increasing during pre-weaning/weaning phases and drastically increasing post-weaning. Culture- independent amplicon surveys identified higher AGF alpha diversity during pre-weaning/ weaning phases, compared to post-weaning. Further, the AGF community structure underwent a drastic shift post-weaning, from a community enriched in the generaKhoyollomyces, Orpinomyces, AL3, and NY8 (some of which commonly encountered in hindgut fermenters) to one enriched in the generaCaecomyces, Piromyces, Pecoramyces, and Cyllamyces, commonly encountered in adult ruminants. Inter-calf community variability was low in the pre- weaning/weaning phases but increased post-weaning. Finally, pairwise comparison of AGF community between calves day 1 post-birth and their mothers suggest a major role for maternal transmission, with additional input from cohabitating subjects. The distinct pattern of AGF progression in calves could best be understood in-light of their narrower niche preferences, metabolic specialization, and physiological optima when compared to bacteria, hence eliciting a unique response to changes in feeding pattern and associated structural development in the GIT of calves during maturation.
A multiplex PCR assay for the detection ofCryptosporidiumspecies and simultaneous differentiation ofCryptosporidium hominis, Cryptosporidium parvumin clinical stool samples
Authors: Katiyar Manish , Padukone Shashiraja , Gulati Reena , Singh Rakesh 
Published: March 2023

AbstractCryptosporidium hominisandCryptosporidium parvumare responsible for more than 90% of the global cryptosporidiosis. Species identification is done by amplification of small subunit ribosomal ribonucleic acid (SSU rRNA) gene, followed by sequencing. We have developed a multiplex polymerase chain reaction (mPCR) assay which detectCryptosporidiumspp. and differentiatesC. hominisandC. parvumfrom stool samples without the need of post amplification sequencing. Nine new set of primers for mPCR assay were designed and the mPCR assay was standardized with known positiveCryptosporidiumDNA template. Best result with three sets of primers that amplifies 436 bp for allCryptosporidiumspp., 577 bp forC. hominisand 287 bp forC. parvum. In addition, thirty-five positive and thirty-five negativeCryptosporidiumstool samples identified by the gold standard nested 18S rRNA PCR-sequencing assay were tested by mPCR. The sensitivity of the mPCR are 100%, 92.9%, and 87.5% forCryptosporidiumspp.,C. hominis, andC. parvumrespectively while specificity is 100% for all the three primers. No cross-reactivity was observed by the new mPCR assay when tested with five known DNA sample ofCystoisospora belliand two known DNA sample ofCyclospora cayetanensis, available in our laboratory from the clinical stool samples. A single species-specific mPCR product ofC. hominisandC. parvumwere sequenced and deposited in GenBank database with the accession noMT862538andMT875168respectively. The mPCR assay is developed which differentiatesC. hominis, andC. parvumin a single test run of amplification and without the need for RFLP or sequencing. Although it less sensitive than 18S rRNA PCR-sequencing assay, but 100% specific, rapid, cost-effective and suitable for making diagnosis of cryptosporidiosis especially in developing countries.HighlightsNovel mPCR assay can detect allCryptosporidiumspeciesThe sensitivity of the mPCR were 100%, 92.9%, and 87.5% for the primers designed to detectCryptosporidiumgenus,C. hominisandC. parvumspecies respectively.No cross reactivity detected with newly developed mPCR assuring 100% specificity.The developed mPCR assay is a robust, specific, reproducible, rapid and cost-effective molecular assay for the diagnosis of cryptosporidiosis.Assay is useful in molecular diagnosis of cryptosporidiosis, especially in developing countries.