bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axons of cortical basket cells originating from dendrites develop higher local complexity than axons emerging from basket cell somata
Authors: Gonda Steffen , Riedel Christian , Reiner Andreas , Köhler Ina , Wahle Petra 
Published: August 2023

AbstractNeuronal differentiation is regulated by neuronal activity. Here, we analyzed dendritic and axonal growth of Basket cells and non-Basket cells using sparse transfection of channelrhodopsin-YFP and repetitive optogenetic stimulation in slice cultures of rat visual cortex. Neocortical interneurons often display axon-carrying dendrites (AcDs). We found that the AcDs of Basket cells and non-Basket cells were on average their most complex dendrite. Further, the AcD configuration had an influence on Basket cell axonal development. Axons originating from an AcD formed denser arborizations with more terminal endings within the dendritic field of the parent cell. Intriguingly, this occurred already in unstimulated Basket cells, and complexity was not increased further by optogenetic stimulation. However, optogenetic stimulation exerted a growth-promoting effect on axons emerging from Basket cell somata. The axons of non-Basket cells neither responded to the AcD configuration nor to the optogenetic stimulation. The results suggest that the formation of locally dense Basket cell plexuses is regulated by spontaneous activity. Moreover, in the AcD configuration, the AcD and the axon it carries mutually support each others growth.TeaserTextbooks usually draw cortical neurons with axons emerging from the cell body. Axons emerging from dendrites have been considered a caprice of nature until recent work demonstrated that axon-carrying dendrites are neither a rare nor a random phenomenon. Rather, this morphological configuration awards specific functional properties. Here, we discovered a morphogenetic role of the AcD configuration in developing Basket neurons which deliver axo-somatic inhibition to pyramidal neurons. Driven by spontaneous activity, AcD and the axon mutually promote each others growth such that the axon rapidly forms a denser presynaptic terminal field. Basket cells with axons from the cell body achieve the same complexity with technical assistance via an optogenetic stimulation. This way, a dendritic origin accelerates Basket cell axonal development.
Nociceptor to macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth
Authors: Fattori Victor , Zaninelli Tiago H. , Rasquel-Oliveira Fernanda S. , Heintz Olivia K. , Jain Ashish , Sun Liang , Seshan Maya L. , Peterse Daniëlle , Lindholm Anne E. , Anchan Raymond M. , Veri Waldiceu A. , Rogers Michael S. 
Published: August 2023

AbstractEndometriosis is a debilitating and painful gynecological inflammatory disease affecting approximately 15% of women. Current treatments are ineffective for a significant fraction of patients, underscoring the need for new medical therapies with long-term benefits. Given the genetic correlation between migraines and endometriosis, we sought evidence for the role of CGRP-mediated neuroimmune communication in endometriosis. We found that mouse and human endometriosis lesions contained CGRP and RAMP1. In mice, nociceptor ablation reduced pain, monocyte recruitment, and lesion size, suggesting that nociceptors support endometriosis lesions.In vitro,CGRP-treated macrophages showed impaired efferocytosis and supported endometrial cell growth in a RAMP1-dependent manner. Treatment with FDA-approved drugs that block CGRP-RAMP1 signaling reduced evoked and spontaneous pain, and lesion size. Since the lack of drug efficacy at reducing ongoing pain drives most endometriosis therapy failure, our data demonstrating effectiveness of non-hormonal and non-opioid CGRP/RAMP1 blocking therapies may lead to clinical benefit for endometriosis patients.
The geometry of photopolymerized topography influences neurite pathfinding by directing growth cone morphology and migration
Authors: Vecchi Joseph T. , Rhomberg Madeline , Guymon C. Allan , Hansen Marlan R. 
Published: August 2023

AbstractCochlear implants (CIs) provide auditory perception to those with profound sensorineural hearing loss: however, the quality of sound perceived by a CI user does not approximate natural hearing. This limitation is due in part to the large physical gap between the stimulating electrodes and their target neurons. Therefore, directing the controlled outgrowth of processes from spiral ganglion neurons (SGNs) into close proximity to the electrode array could provide significantly increased hearing function. For this objective to be properly designed and implemented, the ability and limits of SGN neurites to be guided must first be determined. In this work, we engineered precise topographical microfeatures with angle turn challenges of various geometries to study SGN pathfinding. Additionally, we analyze sensory neurite growth in response to topographically patterned substrates and use live imaging to better understand how neurite growth is guided by these cues. In assessing the ability of neurites to sense and turn in response to topographical cues, we find that the geometry of the angled microfeatures determines the ability of neurites to navigate the angled microfeature turns. SGN neurite pathfinding fidelity can be increased by 20-70% through minor increases in microfeature amplitude (depth) and by 25% if the angle of the patterned turn is made more obtuse. Further, by using engineered topographies and live imaging of dorsal root ganglion neurons (DRGNs), we see that DRGN growth cones change their morphology and migration to become more elongated within microfeatures. However, our observations also indicate complexities in studying neurite turning. First, as the growth cone pathfinds in response to the various cues, the associated neurite often reorients across the angle topographical microfeatures. This reorientation is likely related to the tension the neurite shaft experiences when the growth cone elongates in the microfeature around a turn. Additionally, neurite branching is observed in response to topographical guidance cues, most frequently when turning decisions are most uncertain. Overall, the multi-angle channel micropatterned substrate is a versatile and efficient system to assess SGN neurite turning and pathfinding in response to topographical cues. These findings represent fundamental principles of neurite pathfinding that will be essential to consider for the design of 3D systems aiming to guide neurite growthin vivo.
Age-Associated Weaker Immunity to Coronaviruses is Characteristic of Children that Develop Multisystem Inflammatory Syndrome following SARS-CoV-2 Infection
Authors: Camerini David , Arrieta Antonio , Randall Arlo Z. , Gach Johannes S. , Maecker Holden , Hoang Janet , Imfeld Karen , Osborne Stephanie , Enriquez Claudia , Hung Christopher , Edgar Joshua , Shandling Adam , Huynh Vu , Teng Andy A. , Pablo Jozelyn V. , Forthal Donald N. , Campo Joseph J. , Nugent Diane 
Published: August 2023

AbstractWe analyzed the antibody and cytokine responses of twenty-three patients with multisystem inflammatory syndrome of children (MIS-C) that appeared with a three-to-six-week delay following a mild or asymptomatic SARS-CoV-2 infection. These responses were compared to healthy convalescent pediatric COVID-19 patients approximately twenty-eight days after the onset of symptoms. Both groups had strong IgG responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, but the MIS-C patients had weaker antibody responses to certain epitopes in the SARS-CoV-2 S and N proteins and to the S and N proteins of endemic human coronaviruses (HCoV) compared to pediatric convalescent COVID patients. HCoV antibody reactivity was correlated with age. In contrast, MIS-C patients had elevated serum levels of several proinflammatory cytokines compared to convalescent COVID patients, including interleukins IL-6, IL-8, IL-18 and chemokines CCL2, CCL8, CXCL5, CXCL9 and CXCL10 as well as tumor necrosis factor alpha and interferon gamma. Moreover, many cytokine responses of MIS-C patients were positively correlated with antibody responses to the SARS-CoV-2 S, N, membrane and ORF3a proteins while pediatric convalescent COVID patient cytokine responses were more often negatively correlated with antibody responses to the S, N and ORF3a proteins of SARS-CoV-2.
A subclass of evening cells promotes the switch from arousal to sleep at dusk
Authors: Brown Matthew P. , Verma Shubha , Palmer Isabelle , Zuniga Adler Guerrero , Rosensweig Clark , Keles Mehmet F. , Wu Mark N. 
Published: August 2023

SUMMARYAnimals exhibit rhythmic patterns of behavior that are shaped by an internal circadian clock and the external environment. While light intensity varies across the day, there are particularly robust differences at twilight (dawn/dusk). These periods are also associated with major changes in behavioral states, such as the transition from arousal to sleep. However, the neural mechanisms by which time and environmental conditions promote these behavioral transitions are poorly defined. Here, we show that the E1 subclass ofDrosophilaevening clock neurons promotes the transition from arousal to sleep at dusk. We first demonstrate that the cell-autonomous clocks of E2 neurons alone are required to drive and adjust the phase of evening anticipation, the canonical behavior associated with “evening” clock neurons. We next show that conditionally silencing E1 neurons causes a significant delay in sleep onset after dusk. However, rather than simply promoting sleep, activating E1 neurons produces time- and light- dependent effects on behavior. Activation of E1 neurons has no effect early in the day, but then triggers arousal before dusk and induces sleep after dusk. Strikingly, these phenotypes critically depend on the presence of light during the day. Despite their influence on behavior around dusk,in vivovoltage imaging of E1 neurons reveals that their spiking rate does not vary between dawn and dusk. Moreover, E1-specific clock ablation has no effect on arousal or sleep. Thus, we suggest that, rather than specifying “evening” time, E1 neurons act, in concert with other rhythmic neurons, to promote behavioral transitions at dusk.
Mapping caudolenticular gray matter bridges in the human brain striatum through diffusion magnetic resonance imaging and tractography
Authors: Little Graham , Poirier Charles , Parent Martin , Petit Laurent , Descoteaux Maxime 
Published: August 2023

AbstractIn primates, the putamen and the caudate nucleus are connected by ∼1mm-thick caudolenticular gray matter bridges (CLGBs) interspersed between the white matter bundles of the internal capsule. Little is understood about the functional or microstructural properties of the CLGBs. In studies proposing high resolution diffusion magnetic resolution imaging (dMRI) techniques, CLGBs have been qualitatively identified as an example of superior imaging quality, however, the microstructural properties of these structures have yet to be examined. In this study, it is demonstrated for the first time that dMRI is sensitive to an organized anisotropic signal oriented in the direction parallel to the CLGBs, suggesting that dMRI could be a useful imaging method for probing the microstructure of the CLGBs. To demonstrate the anisotropic diffusion signal is coherently organized along the extent of the CLGBs and to enable a subsequent CLGB microstructural measurement, a novel tractography algorithm is proposed that utilizes the shape of the human striatum (putamen + caudate nucleus) to reconstruct the CLGBs in 3D. The method is applied to two publicly available and one locally acquired diffusion imaging datasets varying in resolution and imaging quality, thereafter demonstrating that the reconstructed CLGBs directly overlap expected gray matter regions in the human brain. In addition, the method is shown to accurately reconstruct CLGBs repeatedly across multiple test-retest cohorts. The novel tractography CLGB reconstructions are then used to extract a quantitative measurement of microstructure from a local model of the diffusion signal along the CLGBs themselves. This is the first work to comprehensively study the CLGBs in-vivo using dMRI and presents techniques suitable for future human neuroscience studies targeting these structures.
Small RNA Analysis of Virus-virus Interaction between Two Orthotospoviruses
Authors: Zhao Kaixi , Islam Md Tariqul , Johnson Nathan R. , Axtell Michael J. , Rosa Cristina 
Published: August 2023

AbstractMixed infections of plant viruses are commonly found in natural patho-systems and present a valuable opportunity to understand how multiple viruses can co-infect the same host. Tomato spotted wilt orthotospovirus (TSWV) and impatiens necrotic spot orthotospovirus (INSV) are present in the same geographic areas and are closely related. More mixed infections of TSWV and INSV have been reported in recent years, and the INSV host range has been reported to be increasing. In a previous study, we have isolated one strain of INSV and one of TSWV and showed that they have an antagonistic relationship in their vectors, but we were unable to determine, the underlying mechanisms governing their antagonismin plantaand the contribution of the host to this. Here, we used small RNA sequencing to study TSWV-INSV antagonistic interaction and showed that INSV alters plant responses and the processing of TSWV.
A defined diet for pre-adultDrosophila melanogaster
Authors: Martelli Felipe , Quig Annelise , Mele Sarah , Lin Jiayi , Fulton Tahlia L. , Wansbrough Mia , Barlow Christopher K. , Schittenhelm Ralf B. , Johnson Travis K. , Piper Matthew D.W. 
Published: August 2023

AbstractDrosophilamelanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this diet is limited to adult studies due to impaired larval development and survival. Here, we provide an adjusted formula that improves larval growth, development rate, and rescues survival. We demonstrate its use for exploring pre-adult diet compositions of therapeutic potential in a model of an inherited metabolic disorder.
Protein Coronas on Functionalized Nanoparticles Enable Quantitative and Precise Large-Scale Deep Plasma Proteomics
Authors: Huang Ting , Wang Jian , Stukalov Alexey , Donovan Margaret K. R. , Ferdosi Shadi , Williamson Lucy , Just Seth , Castro Gabriel , Cantrell Lee S. , Elgierari Eltaher , Benz Ryan W. , Huang Yingxiang , Motamedchaboki Khatereh , Hakimi Amirmansoor , Arrey Tabiwang , Damoc Eugen , Kreimer Simion , Farokhzad Omid C. , Batzoglou Serafim , Siddiqui Asim , Van Eyk Jennifer E. , Hornburg Daniel 
Published: August 2023

AbstractBackgroundThe wide dynamic range of circulating proteins coupled with the diversity of proteoforms present in plasma has historically impeded comprehensive and quantitative characterization of the plasma proteome at scale. Automated nanoparticle (NP) protein corona-based proteomics workflows can efficiently compress the dynamic range of protein abundances into a mass spectrometry (MS)-accessible detection range. This enhances the depth and scalability of quantitative MS-based methods, which can elucidate the molecular mechanisms of biological processes, discover new protein biomarkers, and improve comprehensiveness of MS-based diagnostics.MethodsInvestigating multi-species spike-in experiments and a cohort, we investigated fold-change accuracy, linearity, precision, and statistical power for the using the Proteograph™ Product Suite, a deep plasma proteomics workflow, in conjunction with multiple MS instruments.ResultsWe show that NP-based workflows enable accurate identification (false discovery rate of 1%) of more than 6,000 proteins from plasma (Orbitrap Astral) and, compared to a gold standard neat plasma workflow that is limited to the detection of hundreds of plasma proteins, facilitate quantification of more proteins with accurate fold-changes, high linearity, and precision. Furthermore, we demonstrate high statistical power for the discovery of biomarkers in small- and large-scale cohorts.ConclusionsThe automated NP workflow enables high-throughput, deep, and quantitative plasma proteomics investigation with sufficient power to discover new biomarker signatures with a peptide level resolution.
Disruptive mutations in the serotonin transporter associate serotonin dysfunction with treatment-resistant affective disorder
Authors: Støier Jonatan Fullerton , Jørgensen Trine Nygaard , Sparsø Thomas , Rasmussen Henrik Berg , Kumar Vivek , Newman Amy Hauck , Blakely Randy D. , Werge Thomas , Gether Ulrik , Herborg Freja 
Published: August 2023

ABSTRACTAffective or mood disorders are a leading cause of disability worldwide. The serotonergic system has been heavily implicated in the complex etiology and serves as a therapeutic target. The serotonin transporter (SERT) is a major regulator of serotonin neurotransmission, yet the disease-relevance of impaired SERT function remains unknown. Here, we present the first identification and functional characterization of disruptive coding SERT variants found in patients with psychiatric diseases. In a unique cohort of 144 patients characterized by treatment-resistant chronic affective disorders with a lifetime history of electroconvulsive therapy, we identified two previously uncharacterized coding SERT variants: SERT-N217S and SERT-A500T. Both variants were significantly enriched in the patient cohort compared to GnomAD (SERT-N217S: OR = 151,P= 0.0001 and SERT-A500T: OR = 1348,P= 0.0022) and ethnicity-matched healthy controls (SERT-N217S: OR ≥ 17.7,P≤ 0.013 and SERT-A500T: OR = ∞,P= 0.029). Functional investigations revealed that the mutations exert distinct perturbations to SERT function, but their overall effects converge on a partial loss-of-function molecular phenotype. Thus, the SERT-A500T variant compromises the catalytic activity, while SERT-N217S disrupts proper glycosylation of SERT with a resulting dominant-negative trafficking deficiency. Moreover, we demonstrate that the trafficking deficiency of SERT-N217S is amenable to pharmacochaperoning by noribogaine. Collectively, our findings describe the first disease-associated loss-of-function SERT variants and implicate serotonergic disturbances arising from SERT dysfunction as a risk factor for chronic affective disorders.
A genome-wide association study of adults with community-acquired pneumonia
Authors: Suarez-Pajes Eva , Marcelino-Rodriguez Itahisa , Brito Elisa Hernández , Gonzalez-Barbuzano Silvia , Ramirez-Falcon Melody , Tosco-Herrera Eva , Rubio-Rodríguez Luis A. , Briones María Luisa , Rajas Olga , Borderías Luis , Ferreres Jose , Payeras Antoni , Lorente Leonardo , Aspa Javier , Lorenzo Salazar Jose M. , Valencia-Gallardo José Manuel , Carbonell Edurne , Freixinet Jordi , de Castro Felipe Rodríguez , Violán Jordi Solé , Flores Carlos , Rodríguez-Gallego Carlos 
Published: August 2023

ABSTRACTIntroductionCommunity-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of entry.ObjectiveTo identify genetic risk loci for CAP using a one-stage genome-wide association study (GWAS).MethodsWe performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. Genotyping and imputation allowed testing the association of 7,6 million variants using logistic regressions. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association testing of the classic HLA alleles and amino acids was also conducted.ResultsWe revealed six independent sentinel variants that were genome-wide significant (p<5×10−8), three located on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Our analyses prioritizedC4orf33on 4q28.2,TAPBPon 6p21.32, andZNF341on 20q11.22. Interestingly, genetic defects ofTAPBPandZNF341are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus andHaemophyilus influenzae. Associations were all non-significant for the classic HLA alleles.ConclusionsWe completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.
Mood instability may be causally associated with the high risk of cardiovascular disease: evidence from a mendelian randomization analysis
Authors: Liu Zirui , Wang Haocheng , Yang Zhengkai , Lu Yu , Wang Jikai , Zou Cao 
Published: August 2023

AbstractBackgroundMental illness was identified associated with high risk of cardiovascular diseases (CVDs). However, few studies focused on the effect of personality traits, the causal relationships remain unknown. Here, we use mendelian randomization (MR) analyses to evaluate the causal association between mood instability (mood swings) and 5 common CVDs.MethodsLarge genome-wide association studies (GWAS) of mood swings (n= 373733) and 5 CVDs from two independent cohorts respectively including coronary artery disease (CAD) (n= 766053), myocardial infarction (MI) (n= 596436), heart failure (HF) (n= 1185501), atrial fibrillation (AF) (n= 2169833) and stroke (n = 627558). We performed a range of bidirectional two-sample MR and related sensitive analysis including MR-Egger regression, MR-PRESSO global test and “Leave-one-out” method. A Bonferroni-corrected significance level of p < 0.01 (0.05/5) was identified to be statistically significant, while p < 0.05 was considered to indicate suggestive evidence. Moreover, multivariable MR (MVMR) and mediation analyses were also conducted to adjust confounding factors as well as found potential mediators.ResultsThis MR analyses revealed the significant causal effects of mood swings on CAD (OR = 1.45, 95% CI 1.24–1.71; P = 5.52e-6), MI (OR = 1.60, 95% CI 1.32–1.95; P = 1.77e-6), HF (OR = 1.42, 95% CI 1.12–1.71; P = 2.32e-6) and stroke (OR = 1.48, 95% CI 1.19–1.83; P = 3.46e-4). However, no causal effects of mood swings on AF (P=0.16) were found. In the reverse MR, no causal relationships were observed. Additionally, hypertension may mediate the causal pathway from mood swings to CAD (proportion of mediation effect in total effect: 39.60%, 95% CI: 19.31%–59.89%), MI (35.37%, 95% CI: 17.10%–53.65%), HF (43.19%, 95% CI: 20.68%–65.69%) and stroke (55.47%, 95% CI: 27.00%–83.95%).ConclusionMood instability (mood swings) causally resulted in CAD, MI, HF and stroke, and these causal effects may be partly mediated by hypertension.