bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanosensory stimulation triggers sustained local motor activity inDrosophila melanogaster
Authors: Medeiros Alexandra M. , Hobbiss Anna F. , Borges Gonçalo , Moita Marta , Mendes César S. 
Published: July 2022

AbstractMost vertebrates and invertebrates such as Drosophila melanogaster are able to move in complex environments due to their ability to integrate sensory information along with motor commands. Mechanosensory structures exist along each leg to assist in motor coordination by transmitting external cues or proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers and their underlying circuits remains poorly understood.Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg Mechanosensory Bristles (MsB) and femoral Chordotonal Organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsB triggered sustained cyclic motor activity dependent only on circuits within the Ventral Nerve Cord (VNC). The duration of the MsB-induced movement was dependent on the number of excited cells and specific to leg afferents, since stimulation of MsB in other segments lead to different motor outcomes. MsB-mediated movement lacked inter and intra-leg coordination, but preserved antagonistic muscle activity within joints. Our data shows that sensory stimulation can act in combination with descending commands in order to elicit a faster response to mechanical stimulation. In addition, it sheds light on the ability of specific sensory circuits to modulate motor control, including initiation of movement, presenting a new system to better understand how different levels of coordination are controlled by VNC and central brain locomotor circuits.Significance StatementSensory feedback is critical to allow smooth and stable locomotion. Proprioceptors interact directly with pre-motor centers optimizing and sustaining coordinated movement. However, initiation of moment is considered to be triggered by higher-order centers in the brain. Here we took advantage of the genetic toolkit provided by the fruit fly Drosophila melanogaster to optogenetically activate different classes of leg sensory cells in immobile animals. We found that leg mechanosensory bristles can specifically trigger sustained leg activity independently of higher-order centers as headless flies could sustain prolonged leg movement upon mechanosensory stimulation. Moreover, while this sensory-evoked movement lacks intra- and inter-leg coordination, it still preserved basic antagonistic muscle activity. These findings suggest a parallel mechanism to trigger fast movement upon sensory stimulation. In addition, it provides a new model for movement initiation and a point–of-entry to define pre-motor circuits.
Disentangling the complex gene interaction networks between rice and the blast fungus identifies a new pathogen effector
Authors: Sugihara Yu , Abe Yoshiko , Takagi Hiroki , Abe Akira , Shimizu Motoki , Ito Kazue , Kanzaki Eiko , Oikawa Kaori , Kourelis Jiorgos , Langner Thorsten , Win Joe , Białas Aleksandra , Lüdke Daniel , Contreras Mauricio P. , Chuma Izumi , Saitoh Hiromasa , Kobayashi Michie , Zheng Shuan , Tosa Yukio , Banfield Mark J. , Kamoun Sophien , Terauchi Ryohei , Fujisaki Koki 
Published: July 2022

AbstractStudies focused solely on single organisms can fail to identify the networks underlying host–pathogen gene-for-gene interactions. Here, we integrate genetic analyses of rice (Oryza sativa, host) and rice blast fungus (Magnaporthe oryzae, pathogen) and uncover a new pathogen recognition specificity of the rice nucleotide-binding domain and leucine-rich repeat protein (NLR) immune receptor Pik, which mediates resistance toM. oryzaeexpressing the avirulence effector geneAVR-Pik. Rice Piks-1, encoded by an allele ofPik-1, recognizes a previously unidentified effector encoded by theM. oryzaeavirulence geneAVR-Mgk1, which is found on a mini-chromosome.AVR-Mgk1has no sequence similarity to knownAVR-Pikeffectors, and is prone to deletion from the mini-chromosome mediated by repeatedInago2retrotransposon sequences. AVR-Mgk1 is detected by Piks-1 and by other Pik-1 alleles known to recognize AVR-Pik effectors; recognition is mediated by AVR-Mgk1 binding to the integrated heavy metal-associated (HMA) domain of Piks-1 and other Pik-1 alleles. Our findings highlight how complex gene-for-gene interaction networks can be disentangled by applying forward genetics approaches simultaneously to the host and pathogen. We demonstrate dynamic co-evolution between an NLR integrated domain and multiple families of effector proteins.
Spherical harmonics representation of the steady-state membrane potential shift induced by tDCS in realistic neuron models
Authors: Galan-Gadea Adrià , Salvador Ricardo , Bartolomei Fabrice , Wendling Fabrice , Ruffini Giulio 
Published: July 2022

AbstractObjectiveWe provide a systematic framework for quantifying the effect of externally applied weak electric fields on realistic neuron compartment models as captured by physiologically relevant quantities such as the membrane potential or transmembrane current as a function of the orientation of the field.ApproachWe define a response function as the steady-state change of the membrane potential induced by a canonical external field of 1 V/m as a function of its orientation. We estimate the function values through simulations employing reconstructions of the rat somatosensory cortex from the Blue Brain Project. The response of different cell types is simulated using the NEURON simulation environment. We represent and analyze the angular response as an expansion in spherical harmonics.Main resultsWe report membrane perturbation values comparable to those in the literature, extend them to different cell types, and provide their profiles as spherical harmonic coefficients. We show that at rest, responses are dominated by their dipole terms (ℓ= 1), in agreement with experimental findings and compartment theory. Indeed, we show analytically that for a passive cell, only the dipole term is nonzero. However, while minor, other terms are relevant for states different from resting. In particular, we show howℓ= 0 andℓ= 2 terms can modify the function to induce asymmetries in the response.SignificanceThis work provides a practical framework for the representation of the effects of weak electric fields on different neuron types and their main regions—an important milestone for developing micro- and mesoscale models and optimizing brain stimulation solutions.
Dopamine Activates Astrocytes in Prefrontal Cortex via α1-Adrenergic Receptors
Authors: Pittolo Silvia , Yokoyama Sae , Willoughby Drew D. , Taylor Charlotte R. , Reitman Michael E. , Tse Vincent , Wu Zhaofa , Etchenique Roberto , Li Yulong , Poskanzer Kira E. 
Published: July 2022

SummaryThe prefrontal cortex (PFC) is a hub for cognitive control, and dopamine profoundly influences its functions. In other brain regions, astrocytes sense diverse neurotransmitters and neuromodulators and, in turn, orchestrate regulation of neuroactive substances. However, basic physiology of PFC astrocytes, including which neuromodulatory signals they respond to and how they contribute to PFC function, is lacking. Here, we characterize divergent signaling signatures in astrocytes of PFC and primary sensory cortex in mice, which are linked to differential responsivity to locomotion. We find that PFC astrocytes express receptors for dopamine, but are unresponsive through the Gs/Gi-cAMP pathway. Instead, fast calcium signals in PFC astrocytes are time-locked to dopamine release, and are mediated by α1-adrenergic receptors bothex vivoandin vivo. Further, we describe dopamine-triggered regulation of extracellular ATP at PFC astrocyte territories. Thus, we identify astrocytes as active players in dopaminergic signaling in PFC, contributing to PFC function though neuromodulator receptor crosstalk.Graphical Abstract
A Practical Approach for Optimizing Off-axis Telecentric Digital Holographic Microscope Design
Authors: Jin Lei , Yu Ziyang , Au Aaron , Yip Christopher M. 
Published: July 2022

AbstractDigital holographic microscopy (DHM) has become an attractive imaging tool for the analysis of living cells and histological tissues. The telecentric DHM (TDHM) is a configuration of DHM that lightens the computation load with a priori aberration corrections. However, TDHM requires a well-aligned optical pipeline to optimize its resolution and image quality (IQ), which has traditionally complicated the alignment process. Further deriving from the optical interference functions, we offer a set of methodologies to simplify TDHM design and alignment by determining the optimal +1 order position, which depends on the object-reference beam angle and the interference plane rotation angle. The methods are then experimentally tested and verified on a TDHM system by imaging living HeLa cells in suspension.
APOE ε4 carriage associates with improved myocardial performance in older age
Authors: Topriceanu Constantin-Cristian , Shah Mit , Webber Matthew , Chan Fiona , Moon James C , Richards Marcus , Chaturvedi Nishi , Hughes Alun D. , Schott Jonathan , O’Regan Declan P. , Captur Gabriella 
Published: July 2022

ABSTRACTIntroductionAlthoughAPOE ε4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy).HypothesisCombining data from three British cohorts–1946 National Survey of Health and Development (NSHD), Southall and Brent Revised (SABRE) and UK Biobank–we explored whetherAPOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional parameters by echocardiography and cardiovascular magnetic resonance (CMR) in older age.MethodsBased on the presence ofAPOE ε4, genotypes were divided into:APOE ε4 (ε2ε4, ε3ε4,ε4ε4) and non-APOE ε4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWTs/d, IVSs/d), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). CMR data additionally included longitudinal and radial peak diastolic strain rates (PDSR). Generalized linear models explored associations betweenAPOE ε4 genotypes as exposures and echocardiographic/CMR biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted; Model 2 was adjusted for factors associated with the outcome (age, sex, and socio-economic position) to yield more precise estimates; and subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways.Results35,568 participants were included. Compared to the non-APOE ε4 group,APOE ε4 carriers had similar cardiac echocardiographic phenotypes in terms of LV EF, E/e’, LVPWTs/d, IVSs/dand LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%,p=0.016) which persisted in Model 2 (95% CI 1–7%,p=0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6%; allp<0.070). This was replicated in UK Biobank using CMR data, whereAPOE ε4 carriers had a 1% higher MCF (95% CI 0-1%,p=0.020) which was attenuated only after adjusting for BMI or diabetes.ConclusionsAPOE ε4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium and better longitudinal strain rates compared to nonAPOE ε4 carriers. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed toAPOEε4 carriage that might collectively explain its persistence in humans.
Evaluation of trace elements analysis in Pediatric Patients with COVID-19: A report from Turkey
Authors: Dalkıran Tahir , Unsal Velid , İpek Sevcan , Oncu Dogan , Mercan Mehmet , Kandur Yaşar 
Published: July 2022

AbstractIntroductionThis study aimed to evaluate the levels of Selenium, Copper, and Zinc in an attempt to identify the role of trace elements in pediatric patients with COVID-19 infection.MethodsWe randomly selected 29 patients who were hospitalized with the diagnosis of COVID-19. Blood serum sample was collected to study serum Se, Zn, and Cu levels at disease onset and at the time of discharge.ResultsThe median age of our patients was 71.1 ± 14.4 months (range, 3-205 months); 14 (48.3%) patients were male. The mean CRP, and D-Dimer levels were significantly higher at disease onset than at discharge. On the other hand, the mean Cu, Zn, and Se levels were significantly lower at disease onset compared to the time of discharge. The patients with mild-moderate disease severity were older than the patients with severe disease although the difference did not reach statistical significance (82.2±17.7 vs 54.5± 24.7 months; p=0.374). There was no correlation between age and trace elements other than Zn.ConclusionWe believe that, patients and other individuals under risk of COVID-19 should be supplemented with trace elements.
Extended family with an inherited pathogenic variant in polymerase delta provides strong evidence for recessive effect of proofreading deficiency in human cells
Authors: Andrianova Maria A. , Seplyarskiy Vladimir B. , Terradas Mariona , Sánchez-Heras Ana Beatriz , Mur Pilar , Soto José Luis , Aiza Gemma , Kondrashov Fyodor A. , Kondrashov Alexey S. , Bazykin Georgii A. , Valle Laura 
Published: July 2022

ABSTRACTMutational processes in germline and in somatic cells are vastly different, and it remains unclear how the same genetic background affects somatic and transmissible mutations. Here, we estimate the impact of an inherited pathogenic variant in the exonuclease domain of polymerase delta (Polδ) on somatic and germline mutational processes and cancer development. In germline cells and in non-cancer somatic cells, thePOLD1L474P variant increases the mutation burden only slightly, contributing ∼11.8% and ∼14.7% of mutations respectively, although it strongly distorts the mutational spectra. By contrast, tumors developed by carriers of inherited pathogenic variants inPOLD1harbor a DNA rearrangement that results in a homozygous state of the pathogenic variant, leading to an extremely high mutation rate. Thus, mutations in both alleles ofPOLD1gene are required for strong increase in mutation rate suggesting recessiveness of Poldδ proofreading. These results show a similar role of Polδ in germline and somatic replication, and, together with previous findings, illustrate the important differences between Polδ and Polε in the disruption of their replication fidelity.
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
Authors: Boktor Joseph C. , Sharon Gil , Metman Leo A. Verhagen , Hall Deborah A. , Engen Phillip A. , Zreloff Zoe , Hakim Daniel J. , Bostick John W. , Ousey James , Lange Danielle , Humphrey Gregory , Ackermann Gail , Carlin Martha , Knight Rob , Keshavarzian Ali , Mazmanian Sarkis K. 
Published: July 2022

ABSTRACTBackgroundThe gut microbiome is altered in several neurologic disorders including Parkinson’s disease (PD).ObjectivesProfile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression.MethodsShotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n=48, n=47, respectively), environmental Household Controls (HC, n=29, n=30), and community Population Controls (PC, n=41, n=49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic datasets from two previous studies in Germany and China to determine generalizable microbiome features.ResultsThe gut microbiome in PD shows significant alterations in community composition. Robust taxonomic alterations include depletion of putative “beneficial” gut commensalsFaecalibacterium prausnitziiandEubacteriumandRoseburiaspecies, and increased abundance ofAkkermansia muciniphilaandBifidobacteriumspecies. Pathway enrichment analysis and metabolic potential, constructed from microbial gene abundance, revealed disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism. These global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted inter-community signaling.ConclusionsA metagenomic meta-analysis of PD shows consistent and novel alterations in taxonomic representation, functional metabolic potential, and microbial gene abundance across four independent studies from three continents. These data reveal stereotypic changes in the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research.
A unified model for the surveillance of translation in diverse noncoding sequences
Authors: Kesner Jordan S , Chen Ziheng , Aparicio Alexis A , Wu Xuebing 
Published: July 2022

ABSTRACTTranslation is pervasive outside of canonical coding regions, occurring in lncRNAs, UTRs, and introns. While the resulting polypeptides are often non-functional, translation in noncoding regions is nonetheless necessary for the birth of new coding regions. The mechanisms underlying the surveillance of translation in diverse noncoding regions and how escaped polypeptides evolve new functions remain unclear. Intriguingly, noncoding sequence-derived functional peptides often localize to membranes. Here, we show that the intrinsic nucleotide bias in the noncoding genome and in the genetic code frequently results in polypeptides with a hydrophobic C-terminal tail, which is captured by the ribosome-associated BAG6 membrane protein triage complex for either proteasomal degradation or membrane targeting. In contrast, canonical proteins have evolved to deplete C-terminal hydrophobic residues. Our results uncovered a fail-safe mechanism for the surveillance of unwanted translation from diverse noncoding regions and suggest a possible biochemical route for the preferential membrane localization of newly evolved proteins.HighlightsTranslation in diverse noncoding regions is mitigated by proteasomal degradationC-terminal hydrophobicity is a hallmark of noncoding sequence derived polypeptidesA genome-wide CRISPR screen identified the BAG6 membrane protein triage pathwayRibosome-associated BAG6 complex targets C-terminal hydrophobicity for degradation
De novo discovery of traits co-occurring with chronic obstructive pulmonary disease
Authors: Golovina E. , Fadason T. , Jaros R.K. , Kumar H. , John J. , Burrowes K. , Tawhai M. , O’Sullivan J.M. 
Published: July 2022

AbstractEpidemiological research indicates that chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic lung conditions that are typically accompanied by cardiovascular disease, depression, lung cancer and other conditions. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with COPD and the co-occuring conditions, suggesting common biological mechanisms underlying COPD and these co-occuring conditions. To identify them, we have integrated information across different biological levels (i.e. genetic variants, lung-specific 3D genome structure, gene expression and protein-protein interactions) to build lung-specific gene regulatory and protein-protein interaction networks. We have queried these networks using disease-associated SNPs for COPD, unipolar depression and coronary artery disease. Our results show that COPD-associated SNPs can control genes involved in the regulation of lung or pulmonary function, asthma, brain region volumes, cortical surface area, depressed affect, neuroticism, Parkinson’s disease, white matter microstructure and smoking behaviour. We describe the regulatory connections, genes and biochemical pathways that underly these co-occuring trait-SNP-gene associations. Collectively, our findings provide new avenues for the investigation of the underlying biology and diverse clinical presentations of COPD. In so doing, we identify a collection of genetic variants and genes that may aid COPD patient stratification and treatment.
Transcription of Murine Endogenous Retrovirus MERVL Is Required for Progression of Development in Early Preimplantation Embryos
Authors: Sakashita Akihiko , Kitano Tomohiro , Ishizu Hirotsugu , Guo Youjia , Masuda Harumi , Ariura Masaru , Murano Kensaku , Siomi Haruhiko 
Published: July 2022

AbstractZygotic genome activation (ZGA) is a critical post-fertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL, murine endogenous retrovirus-L, is transiently upregulated at the 2-cell stage around the time of ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we develop a method for consistent knockdown of interspersed copies of MERVL and show that MERVL RNA, but not encoded retroviral proteins and their long terminal repeat (LTR) promoter, is essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. MERVL knockdown (KD) results in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that MERVL-KD embryos retained an accessible chromatin state at, and aberrant expression of, a subset of 2-cell specific genes at mid-preimplantation stages. Taken together, our results suggest a model in which an endogenous retrovirus plays a critical role in regulating host cell fate potential.
What drives prey selection? Assessment of tiger food habits across the Terai-Arc landscape, India
Authors: Biswas Suvankar , Kumar Shrewshree , Bandhopadhyay Meghna , Patel Shiv Kumari , Lyngdoh Salvador , Pandav Bivash , Mondol Samrat 
Published: July 2022

AbstractLarge carnivores strongly shape ecological interactions within their respective ecosystems, but experience significant conflicts with human across their range due to their specific ecological resource requirements. The tiger (Panthera tigris) typifies the challenges faced by the large carnivore communities globally. India retains majority of the global tiger population with significant numbers outside protected areas (PAs) that are involved in conflicts from livestock predation and human/tiger death. To understand the prey selection patterns and spatio-temporal patterns of livestock predation-related conflict issues we investigated tiger food habits across the Indian part of the Terai-Arc Landscape (TAL), a globally-important tiger conservation landscape in India. We used 510 genetically-confirmed tiger faeces collected across the landscape and ascertained 10 wild and livestock as major prey species. Large-bodied species (sambar, swamp deer, nilgai, chital, wild pig and livestock) comprised ~94% of tiger diet, with sambar, chital and livestock were the major prey species. Habitat-specific (Shivalik-Bhabar and Terai) analyses show significantly different pattern of prey selections determined by abundance and prey body weight. Results also suggest that PA and non-PAs of Terai habitat are more prone to livestock depredation-related conflicts, and careful management interventions and community involvements are required to reduce such threats. We suggest long-term plans including population estimation of tigers and prey outside PAs, reducing grazing pressures and cattle enumeration, detailed investigation of tiger deaths etc. to ensure future tiger sustainability across this habitat.