bluuebunny/crossref_metadata_2025_split huggingface dataset:
pCMLM: Genome Wide Association Study of Body Size Traits in Multiple Regions of Yak Based on the Provided Compressed Mixed Linear Model
Authors: Liu Xinrui , Chai Zhixin , Peng Wei , Kangzhu Yixi , Zhong Jincheng , Wang Jiabo 
Published: September 2022

AbstractObjectiveYak is a unique large animal species living in the Qinghai-Tibet Plateau and the surrounding Hengduan Mountains, and has evolved several regional variety resources due to the special geographical and ecological environment in which it lives. Therefore, it is of great importance to investigate the genetic composition of body size traits among breeds in multiple regions for yak breeding and production.MethodA genome-wide association analysis was performed on 94 yak individuals (a total of 31 variety resources) for five body size traits (body height, body weight, body length, chest circumference, and circumference of cannon bone). The individuals were clustered following known population habitat. The kinship of grouping individuals was used in the CMLM. This provided compressed mixed linear model was named pCMLM method.ResultTotal of 3,584,464 high-quality SNP markers were obtained on 30 chromosomes. Principal component analysis using the whole SNPs do not accurately classify all populations into multiple subpopulations, a result that is not the same as the population habitat. Six SNP loci were identified in the pCMLM-based GWAS with statistically significant correlation with body height, and four candidate genes (FXYD6, SOHLH2, ADGRB2, and OSBPL6), which in the vicinity of the variant loci, were screened and annotated. Two of these genes, ADGRB2 and OSBPL6, are involved in biological regulatory processes such as body height regulation, adipocyte proliferation and differentiation.ConclusionBased on the previous population information, the pCMLM can provide more sufficient associated results when the conventional CMLM can not catch optimum clustering groups. The fundamental information for quantitative trait gene localization or candidate gene cloning in the mechanism of yak body size trait formation.
Aminoglycoside tolerance inVibrio choleraeengages translational reprogramming associated with queuosine tRNA modification
Authors: Fruchard Louna , Babosan Anamaria , Carvalho Andre , Lang Manon , Li Blaise , Duchateau Magalie , Giai-Gianetto Quentin , Matondo Mariette , Bonhomme Frédéric , Hatin Isabelle , Arbes Hugo , Fabret Céline , Corler Enora , Sanchez Guillaume , Marchand Virginie , Motorin Yuri , Namy Olivier , de Crécy-Lagard Valérie , Mazel Didier , Baharoglu Zeynep 
Published: September 2022

AbstractTgt is the enzyme modifying the guanine (G) in tRNAs with GUN anticodon to queuosine (Q).tgtis required for optimal growth ofVibrio choleraein the presence of sub-lethal aminoglycoside concentrations. We further explored here the role of the Q34 in the efficiency of codon decoding upon tobramycin exposure. We characterized its impact on the overall bacterial proteome, and elucidated the molecular mechanisms underlying the effects of Q34 modification in antibiotic translational stress response. Using molecular reporters, we showed that Q34 impacts the efficiency of decoding at tyrosine TAT and TAC codons. Proteomics analyses revealed that the anti-SoxR factor RsxA is better translated in the absence oftgt. RsxA displays a codon bias towards tyrosine TAT and overabundance of RsxA leads to decreased expression of genes belonging to SoxR oxidative stress regulon. We also identified conditions that regulatetgtexpression. We propose that regulation of Q34 modification in response to environmental cues leads to translational reprogramming of transcripts bearing a biased tyrosine codon usage.In silicoanalysis further identified candidate genes which could be subject to such translational regulation, among which DNA repair factors. Such transcripts, fitting the definition of modification tunable transcripts, are central in the bacterial response to antibiotics.
Contrary neuronal recalibration in different multisensory cortical areas
Authors: Zeng Fu , Zaidel Adam , Chen Aihua 
Published: September 2022

AbstractThe adult brain demonstrates remarkable multisensory plasticity by dynamically recalibrating information from multiple sensory sources. When a systematic visual-vestibular heading offset is experienced, the unisensory perceptual estimates recalibrate toward each other (in opposite directions) to reduce the conflict. The neural substrate of this recalibration is unknown. Here, we recorded single-neuron activity from the dorsal medial superior temporal (MSTd), parieto-insular vestibular cortex (PIVC), and ventral intraparietal (VIP) areas in three male rhesus macaques during visual-vestibular recalibration. Both visual and vestibular tuning in MSTd recalibrated-each according to their respective cues’ perceptual shifts. Vestibular tuning in PIVC also recalibrated together with corresponding perceptual shifts (cells were not visually tuned). By contrast, VIP neurons demonstrated a unique phenomenon: both vestibular and visual tuning recalibrated according to vestibular perceptual shifts. Such that, visual tuning shifted, surprisingly, contrary to visual perceptual shifts. Therefore, while unsupervised recalibration (to reduce cue conflict) occurs in early multisensory cortices, higher-level VIP reflects only a global shift, in vestibular space.In Brief:The neural bases of multisensory plasticity are currently unknown. Here, Zeng et al. studied neuronal recalibration to a systematic visual-vestibular cue conflict. In multisensory cortical areas MSTd and PIVC, single-unit responses to visual and vestibular stimuli recalibrated to reduce the cue conflict, along with their respective unisensory perceptual shifts. By contrast, in higher-level VIP, both visual and vestibular neuronal responses recalibrated with vestibular perceptual shifts. This led to a surprising recalibration of visual responses opposite in direction to visual perceptual shifts. This exposes differential aspects of multisensory plasticity across multisensory cortical areas, and reveals a novel hybrid of visual responses within a vestibular reference frame in parietal neurons.HighlightsIn the presence of a systematic heading conflict, visual and vestibular cues recalibrate towards one another to reduce the conflict.In MSTd, neuronal responses to vestibular and visual cues recalibrated, each according to their respective cues’ perceptual shifts.In PIVC, vestibular responses recalibrated according to vestibular perceptual shifts (cells were not visually tuned).In VIP, neuronal responses to both vestibular and visual cues recalibrated together with vestibular perceptual shifts (opposite in direction to visual perceptual shifts).Profound differences in neuronal recalibration expose different functions across multisensory cortical areas.
Therapeutic potential of rWnt5A in curbingLeishmania donovaniinfection
Authors: Maity Shreyasi , Sen Malini 
Published: September 2022

AbstractIn this study, we demonstrated that administration of recombinant Wnt5A (rWnt5A) toLeishmania donovani(L. donovani) infected RAW 264.7 macrophages cause a significant reduction of infection that is associated with an increase in both cellular reactive oxygen species (ROS) and secreted IFN-γ/IL-10 ratio. Furthermore, rWnt5A administration appreciably blocks the progression ofL. donovaniinfection established in a mouse model. This line of defensein vivois associated with an elevation in immune cell associated ROS, and an activated T cell profile marked by increased IFN-γ and Granzyme B expression. As a corollary, infection associated disruption of splenic white pulp organization is markedly restrained. In summary, this study unveils the therapeutic potential of rWnt5A in curbingL. donovaniinfection and the progression of experimental visceral leishmaniasis through immune cell signaling. Additionally, it opens up new avenues of investigation into the use of rWnt5A as a therapeutic agent for restraining progression of the drug resistant refractory disease.
Magnesium and the magnesium transporter UEX regulate sleep via Ca2+-dependent CREB signaling and a CNK-ERK pathway
Authors: Yuan Xin , Zheng Huimei , Xu Xiao , Deng Huan , Yang Xiaohang , Xi Yongmei 
Published: September 2022

AbstractMagnesium and its related preparations are already in medical use and have recognized therapeutic effects on sleep disorders. However, its underlying molecular mechanisms remain unclear. Here, usingDrosophilaas a model, we found that RNAi-mediated knockdown ofUex, the homologous gene of magnesium transporters of the Cyclin M family (CNNM) causes increased daily total sleep. Ectopic-expression of CNNM1 can rescue the sleep phenotype inUexknockdown flies. UEX exhibits rhythmic oscillations in the brain and affects the efflux of cellular Mg2+. Knockdown ofUexin the nervous system influences Ca2+-mediated CREB signaling and neuroplasticity. Additionally, Uex physically interacts with CNK, the upstream regulator of ERK pathway. Similar effects on sleep are observed with knockdown ofCnkin flies. We propose that the UEX regulates sleep through its downstream Ca2+-dependent CREB signaling and a CNK-ERK pathway. Our findings may provide new insight into mechanisms of magnesium and magnesium transporter related sleep disorder.
Preserved neural population dynamics across animals performing similar behaviour
Authors: Safaie Mostafa , Chang Joanna C. , Park Junchol , Miller Lee E. , Dudman Joshua T. , Perich Matthew G. , Gallego Juan A. 
Published: September 2022

AbstractAnimals of the same species often exhibit similar behaviours that are advantageously adapted to their body and their environment. These behaviours are shaped by selection pressures over evolutionary timescales at the species level, yet each individual produces these behaviours using a different, uniquely constructed brain. It remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of a given individual. Here, we hypothesised that the adaptive behaviour of a species requires specific neural population ‘latent dynamics’. These latent dynamics should thus be preserved and identifiable across individuals within a species, regardless of the idiosyncratic aspects of each individual’s brain. Using recordings of neural populations from monkey and mouse motor cortex, we show that individuals from the same species share surprisingly similar neural dynamics when they perform the same behaviour. The similarity in neural population dynamics extends beyond cortical regions to the dorsal striatum, an evolutionarily older structure, and also holds when animals con-sciously plan future movements without overt behaviour. These preserved dynamics are behaviourally-relevant, allowing decoding of intended and ongoing movements across individuals. We posit that these emergent neural population dynamics result from evolutionarily-imposed constraints on brain development, and reflect a fundamental property of the neural basis of behaviour.
Early parafoveal semantic integration in natural reading
Authors: Pan Yali , Frisson Steven , Federmeier Kara D. , Jensen Ole 
Published: September 2022

AbstractHumans can read and comprehend text rapidly, implying that readers might process multiple words per fixation. However, the extent to which parafoveal words are previewed and integrated into the evolving sentence context remains disputed. We investigated parafoveal processing during natural reading by recording brain activity and eye movements using MEG and an eye tracker while participants silently read one-line sentences. The sentences contained an unpredictable target word that was either congruent or incongruent with the sentence context. To measure parafoveal processing, we flickered the target words at 60 Hz and measured the resulting brain responses (i.e.,Rapid Invisible Frequency Tagging, RIFT) during fixations on the pre-target words. Our results revealed a significantly weaker tagging response for target words that were incongruent with the previous context compared to congruent ones, even within 100 ms of fixating the word immediately preceding the target. This reduction in the RIFT response was also found to be predictive of individual reading speed. We conclude that semantic information is not only extracted from the parafovea but can also be integrated with the previous context before the word is fixated. This early and extensive parafoveal processing supports the rapid word processing required for natural reading. Our study suggests that theoretical frameworks of natural reading should incorporate the concept of deep parafoveal processing.
3D Printed Skull Cap and Benchtop Fabricated Microwire-based Microelectrode Array for Custom Rat Brain Recordings
Authors: Yi Dongyang , Hartner Jeremiah P. , Ung Brian S. , Zhu Harrison L. , Watson Brendon O. , Chen Lei 
Published: September 2022

AbstractMicrowire microelectrode arrays (MEAs) have been a popular low-cost tool for chronic electrophysiological recordings. Multi-MEA implantations can reveal electrical dynamics crucial to brain function. However, both the fabrication and implantation procedures for multi-MEAs on a single rodent are time-consuming and highly manual skill-dependent for quality. To enable in-house design, fabrication, and implantation of custom microwire MEAs, we developed (1) a computer-aided designed and 3D printed skull cap for pre-determined implantation locations of each MEA and (2) a benchtop fabrication approach for low-cost custom microwire MEAs. A proof-of-concept design of 32-channel 4-MEA (8-wire each) recording system was prototyped and tested through Sprague Dawley rat recordings. The skull cap design based on CT-scan of single rat conforms well with multiple Sprague Dawley rats of various size, age, and weight with minimal bregma alignment error. The prototyped 32-channel system were able to record spiking activities over 5 months. In comparison with conventional stereotactic surgeries, the skull cap system simplifies the implantation location alignment for each MEA by embedding them into the pre-printed designs, thus dramatically reducing the surgical time and effort and increasing the accuracy and repeatability. Compared to commercially available custom microwire MEAs, this in-house fabrication method enables neuroscience labs to create a custom recording apparatus with lower cost and shorter lead time for design modifications. A new methodology for neuroscience labs to fabricate and insert custom microwire MEAs has been developed and it could be easily generalized to enable low-cost highly-custom multi-region recording/stimulation studies.Highlights3D printed skull caps as implantation platform for multi-region rat brain recordingComputer-aided design for custom cap geometry and predetermined implantation locationBenchtop microwire fabrication approach for in-house custom microelectrode arraysDuplicable and generalizable design, fabrication, and implantation methodologies
Personalized transcranial alternating current stimulation improves sleep quality: Initial Findings
Authors: Ayanampudi V. , Kumar V. , Krishnan A. , Walker M.P. , Ivry R.B. , Knight R.T. , Gurumoorthy R. 
Published: September 2022

AbstractInsufficient sleep is a major health issue. Inadequate sleep is associated with an array of poor health outcomes, including cardiovascular disease, diabetes, obesity, certain forms of cancer, Alzheimer’s disease, depression, anxiety, and suicidality. Given concerns with typical sedative hypnotic drugs for treating sleep difficulties, there is a compelling need for added alternative interventions. Here, we report results of a non-invasive electrical brain stimulation approach to optimizing sleep involving transcranial alternating current stimulation (tACS).A total of 25 participants (mean age: 46.3, S.D. ±12.4, 15 females) were recruited for a null-stimulation controlled (Control condition), within subjects, randomized crossed design, that included two variants of an active condition involving 15 minutes pre-sleep tACS stimulation. To evaluate the impact on sleep quality, the two active tACS stimulation conditions were designed to modulate sleep-dependent neural activity in the theta/alpha frequency bands, with both stimulation types applied to all subjects in separate sessions. The first tACS condition used a fixed stimulation pattern across all participants, a pattern composed of stimulation at 5Hz and 10Hz. The second tACS condition used a personalized stimulation approach with the stimulation frequencies determined by each individual’s peak EEG frequencies in the 4-6Hz and 9-11Hz bands.Personalized tACS stimulation increased sleep quantity (duration) by 22 minutes compared to a Control condition (p=.04), and 19 minutes compared to Fixed tACS stimulation (p=.03). Fixed stimulation did not significantly increase sleep duration compared to Control (mean: 3 minutes; p=0.75). For sleep onset, the Personalized tACS stimulation resulted in reducing the onset by 28% compared to the Fixed tACS stimulation (6 minutes faster, p=.02). For a Poor Sleep sub-group (n=13) categorized with Clinical Insomnia and with a high insomnia severity, Personalized tACS stimulation improved sleep duration by 33 minutes compared to Fixed stimulation (p=0.02), and 30 minutes compared to Control condition (p<0.1).Together, these results suggest that Personalized stimulation improves sleep quantity and time taken to fall asleep relative to Control and Fixed stimulation providing motivation for larger-scale trials for Personalized tACS as a sleep therapeutic, including for those with insomnia.
A highly expressed odorant receptor from the yellow fever mosquito, AaegOR11, responds to (+)- and (-)-fenchone and a phenolic repellent
Authors: Lu WeiYu , Leal Walter S. , Brisco Katherine K. , An Sunny , Cornel Anthony J. 
Published: September 2022

AbstractThe cornerstone of the reverse chemical ecology approach is the identification of odorant receptors (OR) sensitive to compounds in a large panel of odorants. In this approach, we de-orphanize ORs and, subsequently, measure behaviors elicited by these semiochemicals. After that, we evaluate behaviorally active compounds for applications in insect vector management. Intriguingly, multiple ORs encoded by genes highly expressed in mosquito antennae do not respond to any test odorant. One such case is CquiOR125 from the southern house mosquito, Culex quinquefasciatus Say. To better understand CquiOR125’s role in Culex mosquito olfaction, we have cloned a CquiOR125 orthologue in the genome of the yellow fever mosquito, Aedes aegypti (L.), AaegOR11. Unlike the unresponsive nature of the orthologue in Cx. quinquefasciatus, oocytes co-expressing AaegOR11 and AaegOrco elicited robust responses when challenged with fenchone, 2,3-dimethylphenol, 3,4-dimethylphenol, 4-methycyclohexanol, and acetophenone. AlphaFold models showed that AaegOR11 and CquiOR125 share structural homolog cores with MhraOR5, the only insect OR structure (PDB: 7LID) elucidated to date. Interestingly, AaegOR11 responded strongly and equally to (+)- and (-)-fenchone, with no chiral discrimination. Contrary to reports in the literature, fenchone did not show any repellency activity against Ae. aegypti or Cx. quinquefasciatus. Laboratory and field tests did not show significant increases in egg captures in cups filled with fenchone solutions compared to control cups. The second most potent ligand, 2,3-dimethylphenol, showed repellency activity stronger than that elicited by DEET at the same dose. We, therefore, concluded that AaegOR11 is a mosquito repellent sensor. It is feasible that CquiOR125 responds to repellents that remain elusive.
Context-dependent requirement of G protein coupling for Latrophilin-2 in target selection of hippocampal axons
Authors: Pederick Daniel T. , Perry-Hauser Nicole A. , Meng Huyan , He Zhigang , Javitch Jonathan A. , Luo Liqun 
Published: September 2022

ABSTRACTThe formation of neural circuits requires extensive interactions of cell-surface proteins to guide axons to their correct target neurons. Trans-cellular interactions of the adhesion G protein-coupled receptor latrophilin-2 (Lphn2) with its partner teneurin-3 instruct the precise assembly of hippocampal networks by reciprocal repulsion. Lphn2 acts as a receptor in distal CA1 neurons to direct their axons to proximal subiculum, and as a repulsive ligand in proximal subiculum to direct proximal CA1 axons to distal subiculum. It remains unclear if Lphn2-mediated intracellular signaling is required for its role in either context. Here, we show that Lphn2 couples to Gα12/13 in heterologous cells, which is increased by constitutive exposure of the tethered agonist. Specific mutations of Lphn2’s tethered agonist region disrupt its G protein coupling and autoproteolytic cleavage, whereas mutating the autoproteolytic cleavage site prevents cleavage but preserves a functional tethered agonist. Using an in vivo misexpression assay, we demonstrate that wild-type Lphn2 misdirects proximal CA1 axons to proximal subiculum and that Lphn2 tethered agonist activity is required for its role as a repulsive receptor. By contrast, neither tethered agonist activity nor autoproteolysis was necessary for Lphn2’s role as a repulsive ligand. Thus, tethered agonist activity is required for Lphn2-mediated neural circuit assembly in a context-dependent manner.
Transposase N-terminal phosphorylation and asymmetric transposon ends inhibit piggyBac transposition in mammalian cells
Authors: Luo Wentian , Hickman Alison B. , Genzor Pavol , Ghirlando Rodolfo , Furman Christopher M. , Menshikh Anna , Haase Astrid , Dyda Fred , Wilson Matthew H. 
Published: September 2022

AbstractMechanistic regulation of DNA transposon systems in mammalian cells remains poorly understood. Using modeling, biochemical, and cell-based assays, we sought to extend the recent cryoEM structural insight into the piggyBac transpososome to evaluate the previously unexplained role of the transposase N-terminus, the need for asymmetric transposon ends, and the complexity of transposase tetramer formation for transposition in mammalian cells. We found that N-terminal phosphorylation by casein kinase II inhibits transposase-DNA interaction and designed deletion of this phosphorylated domain releases inhibition thereby enhancing activity. We also found that the N-terminal domain promotes transposase dimerization in the absence of transposon DNA. N-terminal deletion enables transposition of symmetric transposon ends that was previously not achievable with piggyBac. The complex transposase tetramer needed for transposition of asymmetric transposon ends can be overcome via appending a second transposase C-terminal domain in combination with symmetric transposon ends overcoming the negative regulation by asymmetric ends. Our results demonstrate that N-terminal transposase phosphorylation and the requirement for asymmetric transposon ends both negatively regulate piggyBac transposons in mammalian cells. These novel insights into mechanism and structure of the piggyBac transposase expand its potential use for genomic applications.