bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial photobiomodulation enhances visual working memory capacity in humans
Authors: Zhao Chenguang , Li Dongwei , Kong Yuanjun , Liu Hongyu , Hu Yiqing , Niu Haijing , Jensen Ole , Li Xiaoli , Liu Hanli , Song Yan 
Published: February 2022

AbstractTranscranial photobiomodulation (tPBM) is a novel and noninvasive intervention, which has shown promise for improving cognitive performances. Whether tPBM can modulate brain activity and thereby enhance working memory (WM) capacity in humans remains unclear. In this study, we delivered double-blind and sham-control tPBM with different wavelengths to the prefrontal cortex (PFC) in 90 healthy participants and conducted four electroencephalography (EEG) experiments to investigate whether individual visual working memory capacity and related neural response could be modulated. We found that 1064 nm tPBM applied to the right PFC has both a substantial impact on visual working memory capacity and occipitoparietal contralateral delay activity (CDA), no matter orientation or color feature of the memorized objects. Importantly, the CDA set-size effect during the retention mediated the effect between 1064 nm tPBM and subsequent WM performance. However, these behavioral benefits and the corresponding changes of CDA set-size effect were absent with tPBM at 852 nm wavelength or with the stimulation on the left PFC. Our findings provide converging evidence that 1064 nm tPBM applied on the right PFC can improve visual working memory capacity, as well as explain the individual’s electrophysiological changes about behavioral benefits.
The circ_0002538/miR-138-5p/PLLP axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy
Authors: Liu Yutian , Xu Zhao , Liu Wei , Ren Sen , Xiong Hewei , Jiang Tao , Chen Jing , Kang Yu , Li Qianyun , Wu Zihan , Machens Hans-Gu□nther , Yang Xiaofan , Chen Zhenbing 
Published: February 2022

AbstractDiabetic peripheral neuropathy (DPN) is the most common complication of diabetes, but the underlying molecular pathogenesis remains unclear. Accumulating evidence indicates that circular RNAs (circRNAs) play vital roles in DPN, while their expressions and functions in Schwann cell (SC) are rarely reported. Here, we performed protein profiling and circRNA sequencing on the peripheral nerves of patients with or without DPN. A total of 265 differentially expressed proteins were identified in DPN by protein profiling, which mainly enrich in myelination according to Gene Ontology analysis. Further, 15637 circRNAs were identified by circRNA sequencing, of which 11 were verified to be dysregulated. Among them, circ_0002538 was found to be downregulated in DPN and chosen for further investigation. Functional experiments revealed that circ_0002538 overexpression promoted SC migration and relieved demyelination in DPN. Mechanistic studies revealed that circ_0002538 could promote PLLP expression by sponging miR-138-5p, while lack of circ_0002538 led to PLLP deficiency, which further suppressed SC migration and caused demyelination. The present research provided novel insights into the pathogenesis of DPN, in which the circ_0002538/miR-138-5p/PLLP axis was suppressed in SCs and hence caused demyelination. These findings expanded the role of circRNAs in DPN and provided potential therapeutic targets for DPN.
iPSC-based modeling of THD recapitulates disease phenotypes and reveals neuronal malformation
Authors: Tristán-Noguero Alba , Fernández-Carasa Irene , Calatayud Carles , Bermejo-Casadesús Cristina , Campa Leticia , Artigas Francesc , Domingo-Jiménez Rosario , Ibáñez Salvador , Pineda Mercè , Artuch Rafael , Raya Ángel , García-Cazorla Àngels , Consiglio Antonella 
Published: February 2022

AbstractTyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early-onset parkinsonism. Affected children present with either a severe form that does not respond to L-Dopa treatment (THD-B), or a milder L-Dopa responsive form (THD-A). We generated induced pluripotent stem cells (iPSCs) from THD patients that were differentiated into dopaminergic neurons (DAn) and compared with control-DAn from healthy individuals and gene-corrected isogenic controls. Consistent with patients, THD iPSC-DAn displayed lower levels of DA metabolites and reduced TH expression, when compared to controls. Moreover, THD iPSC-DAn showed abnormal morphology, including reduced total neurite length and either an abnormal TH proximodistal gradient (THDA), or neurite arborization defects (THDB). Treatment of THD-iPSC-DAn with L-Dopa rescued the neuronal defects and disease phenotype only in THDA-DAn. Interestingly, L-Dopa treatment at the stage of neuronal precursors could prevent the alterations in THDB-iPSC-DAn, thus suggesting the existence of a critical developmental window in THD. Our iPSC-based model recapitulates THD disease phenotypes and response to treatment, representing a promising tool for investigating pathogenic mechanisms, drug screening, and personalized management.
Copepod functional traits and groups show divergent biogeographies in the global ocean
Authors: Benedetti Fabio , Wydler Jonas , Vogt Meike 
Published: February 2022

AbstractAimThe distribution of zooplankton functional traits is a key factor for regulating food web dynamics and carbon cycling in the oceans. Yet, we lack a clear understanding of how many functional groups (FGs) exist in the zooplankton and how their traits are distributed on a global scale. Here, we model and map the environmental habitats of copepod (i.e. the main component of marine zooplankton) FGs to identify regions sharing similar functional trait expression, at the community level.TaxonMarine planktonic Neocopepoda.LocationGlobal ocean.MethodsFactor analysis on mixed data and hierarchical clustering were used to identify copepod FGs based on five species-level functional traits. An ensemble of species distribution models was used to estimate the environmental niches of the species modelled and the community weighted mean values of the traits studied. Ocean regions were defined based on their community-level mean trait expression using a principal component analysis and hierarchical clustering.ResultsEleven global copepod FGs were identified. They displayed contrasting latitudinal patterns in mean annual habitat suitability that could be explained by differences in environmental niche preferences: two FGs were associated with polar conditions, one followed the global temperature gradient, five were associated with tropical oligotrophic gyres, and the remaining three with boundary currents and counter currents. Four main regions of varying community weighted mean trait values emerged: the Southern Ocean, the northern and southern high latitudes, the tropical gyres, and the boundary currents and upwelling systems.ConclusionsThe present FGs will improve the representation of copepods in global marine ecosystem models. This study improves the understanding of the patterns and drivers of copepods trait biogeography and will serve as a basis for studying links between zooplankton biodiversity and ecosystem functioning in a context of climate change.
Database-independent analysis of probable post-translational modifications of soil proteins across ecosystems
Authors: Starke Robert , Schäpe Stephanie Serena , van den Bossche Tim , Martinovic Tijana , Parente Fernandes Maysa Lima , Delgado-Baquerizo Manuel , Bastida Felipe , Jehmlich Nico 
Published: February 2022

AbstractThe identification rate of measured peptide spectra to proteins barely scratches 1% in best-case scenarios. Hundreds of thousands of valuable spectra are lost as no viable match in the database is found. Here, we apply the delta m/z plot that was previously implemented in MSnbase as tool for quality control to 63 soil samples from three ecosystems with different vegetation (39 forests, 11 grasslands, and 13 shrublands) with the aim to extract probable post-translational modifications (PTM) without the need of a reference database. The validity of the approach was verified with amino acids proposed for their respective 1 Da mass interval and compared to their relative abundance in proteins. We found that the average probable PTM and most known PTMs proposed for the mass intervals are similar across ecosystems. Otherwise, 11 mass intervals changed significantly in relative abundance in the three ecosystems but only for one an annotation could be proposed. Our approach not only highlights the opportunity of the database-independent analysis in soil metaproteomics but paves the way for targeted analysis of the yet unknown PTMs.
EagleImp-Web: A Fast and Secure Genotype Phasing and Imputation Web Service using Field-Programmable Gate Arrays
Authors: Wienbrandt Lars , Prieß Christoph , Kässens Jan Christian , Franke Andre , Uhing Franziska , Ellinghaus David 
Published: February 2022

AbstractImputation web servers have been developed that allow phasing and imputation of genome-wide data without the need for own computing resources. However, their terms of use, data sharing with third parties, the security architecture of the web service, and the algorithms and parameter settings used are only partially disclosed. We developed EagleImp-Web, a fast, secure and convenient web service for phasing and imputation of genome-wide data. The web service uses technical improvements in phasing and imputation algorithms and a field-programmable gate array (FPGA) accelerator design to reduce computation time without loss of phasing and imputation quality. Other key features include no exposure of user information and input/output data to third parties, high data security and fast secure download, user authentication through 2-factor authentication, full control in managing user accounts, and full transparency of algorithms and their settings. EagleImp-Web provides simple and convenient functionalities for monitoring running jobs and selecting parameter settings and output information. Due to the speed advantage over a purely CPU-based implementation, EagleImp-Web offers the user the ability to choose a more resource-intensive parameter setting in exchange for computation time to further improve phasing and imputation quality. EagleImp-Web is freely availabe at https://hybridcomputing.ikmb.uni-kiel.de.
Organotopic Organization of the Cervical Vagus Nerve
Authors: Thompson Nicole , Ravagli Enrico , Mastitskaya Svetlana , Iacoviello Francesco , Stathopoulou Thaleia-Rengina , Perkins Justin , Shearing Paul R. , Aristovich Kirill , Holder David 
Published: February 2022

AbstractDespite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N=4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders and more.
Phospho-proteomic analysis of CAR-T cell signaling following activation by antigen-presenting cancer cells
Authors: MacMullan Melanie A. , Dunn Zachary S. , Qu Yun , Wang Pin , Graham Nicholas A. 
Published: February 2022

AbstractChimeric antigen receptors (CARs) are synthetic biomolecules comprised of an extracellular antigen recognition domain and intracellular signaling domains. When expressed in immune cells, CARs direct their host cells to kill diseased cells expressing the antigen recognized by the CAR. Although signaling pathways downstream of CAR activation control the cytotoxic function of CAR-expressing cells, phospho-proteomic studies of CAR signaling have been limited. Most approaches have used antibodies or soluble ligands, rather than cell-displayed antigens, to activate CAR signaling. Here, we demonstrate an efficient and cost-effective label-free phospho-proteomic approach to analyze CAR signaling in immune cells stimulated with antigen-presenting cancer cells. Following co-culture of CAR-T cells with cancer cells, we first preserve phospho-signaling by cross-linking proteins with formalin. Then, we use magnet-activated cell sorting (MACS) to isolate CAR-T cells from the co-culture. Validation experiments demonstrated that formalin fixation did not alter the phospho-proteome and that MACS achieved >90% CAR-T cell purity. Next, we compared the phospho-proteome in CAR-T cells stimulated with either CD19-expressing or non-CD19-expressing SKOV3 ovarian cancer cells. This analysis revealed that CAR signaling activated known pathways including the mitogen- activated protein kinases (MAPKs) ERK1/2. Bioinformatic approaches further showed that CAR activation induced other signaling pathways including the MAPK p38α, protein kinase A, and checkpoint kinase 1 (CHK1). Taken together, this work presents an easy and inexpensive method to better understand CAR immunotherapy by label-free phospho-proteomic analysis of CAR signaling in immune cells stimulated by antigen- presenting cancer cells.
Load Non-Linearly Modulates Movement Reflex Gain in an Insect Leg via a Distributed Network of Identified Nonspiking Interneurons
Authors: Gebehart Corinna , Hooper Scott L. , Büschges Ansgar 
Published: February 2022

ABSTRACTProducing context-specific motor acts requires sensorimotor neural networks to integrate multiple sensory modalities. Some of this integration occurs via presynaptic interactions between proprioceptive afferent neurons themselves,1,2 other by afferents of different modalities targeting appropriate motor neurons (MNs).3–5 How the interneuronal network typically interposed between sensory afferents and MNs contributes to this integration, particularly at single-neuron resolution, is much less understood. In stick insects, this network contains nonspiking interneurons (NSIs) converging onto the posture-controlling slow extensor tibiae motor neuron (SETi). We analyzed how load altered movement signal processing by tracing the interaction of movement (femoral chordotonal organ, fCO) and load (tibial campaniform sensilla, tiCS) signals from the afferents through the NSI network to the motor output. On the afferent level, load reduced movement signal gain by presynaptic inhibition; tiCS stimulation elicited primary afferent depolarization and reduced fCO afferent action potential amplitude. In the NSI network, graded responses to movement and load inputs summed nonlinearly and increased the gain of NSIs opposing movement-induced reflexes. The gain of SETi and muscle movement reflex responses consequently decreased. Gain modulation was movement parameter-specific and required presynaptic inhibition; pharmacologically blocking presynaptic inhibition abolished load-dependent tuning of SETi responses. These data describe sensorimotor gain control at the sensory, premotor, and motor levels. Presynaptic inhibition-mediated nonlinear integration allowed the NSI network to respond to movement sensory input in a context (load)-dependent manner. These findings show how gain changes can allow premotor networks to integrate multiple sensory modalities and thus generate context-appropriate motor activity.
ABIOTIC STRESS GENE 1 mediates aroma volatiles accumulation by activating MdLOX1a in apple
Authors: Zhang Jing , Zhang Susu , Wang Yongxu , Zhang Shuhui , Liu Wenjun , Wang Nan , Fang Hongcheng , Zhang Zongying , Chen Xuesen 
Published: February 2022

ABSTRACTFruit aroma is an important organoleptic quality, which influences consumer preference and market competitiveness. Aroma compound synthesis pathways in plants have been widely identified of which the lipoxygenase pathway is crucial for fatty acid catabolism to form esters in apple. However, the regulatory mechanism of this pathway remains elusive. In this study, linear regression analysis and transgene verification revealed that the lipoxygenase MdLOX1a participates in ester biosynthesis. Yeast one-hybrid library screening indicated that a novel abiotic stress gene, MdASG1 (ABIOTIC STRESS GENE 1), was a positive regulator of the MdLOX1a promoter and ester production based on yeast one-hybrid and dual-luciferase assays, and correlation analysis among eight apple cultivars. Overexpression of MdASG1 in apple and tomato stimulated the lipoxygenase pathway and increased the fatty acid-derived volatile content, whereas the latter was decreased by MdASG1 silencing. Furthermore, MdASG1 overexpression enhanced the salt-stress tolerance of tomato and apple ‘Orin’ calli accompanied by a higher content of fatty acid-derived volatiles compared with that of non-stressed transgenic tomato fruit. Collectively, these findings indicate that MdASG1 activates MdLOX1a expression and participates in the lipoxygenase pathway, subsequently increasing the accumulation of aroma compounds especially under moderate salt stress treatment. The results also provide insight into the regulation of aroma production, and the potential strategy of prudent development and utilization of saline-alkali land to produce high-quality fruit, thereby reducing pressure on arable land and ensuring national food security.One-sentence SummaryMdASG1 directly activates MdLOX1a expression to promote aroma volatiles accumulation especially under moderate salt stress.
Differential recognition of computationally optimized H3 hemagglutinin influenza vaccine candidates by human antibodies
Authors: Abbadi Nada , Nagashima Kaito , Pena-Briseno Alma , Ross Ted M. , Mousa Jarrod J. 
Published: February 2022

AbstractAmong circulating influenza viruses in humans, H3N2 viruses typically evolve faster than other subtypes and have caused severe illness and deaths in millions of people since emerging in 1968. Computationally optimized broadly reactive antigen (COBRA) technology is one strategy to broaden vaccine-elicited antibody responses among influenza subtypes. In this study, we determined the structural integrity of an H3N2 COBRA HA, TJ5, and, as nearly all humans have pre-existing immunity to H3N2 influenza viruses, we probed the antigenic profile of several H3N2 COBRA HAs by assessing recognition of these immunogens by human B cells and monoclonal antibodies (mAbs). Of three recently described COBRA H3 HA antigens (TJ5, NG2, and J4), we determined that TJ5 and J4 HA proteins recognize pre-existing B cells (from the 2017-2018 vaccine season) more effectively than NG2 HA and a wild type Hong Kong/4801/2014 protein. H3 HA-specific human mAbs recognize wild type and COBRA HA proteins, and have functional activity against a broad panel of H3N2 viruses. mAb TJ5-5 recognizes TJ5 and J4 HA proteins, but has poor recognition of NG2 HA, similar to the global B cell analysis. To probe these recognition differences and to verify the structural integrity of the TJ5 HA protein, we determined a 3.4 Å structure via cryo-electron microscopy of TJ5-5 complexed with the TJ5 HA, which revealed residues important to the differential binding. Overall, these studies determined that COBRA H3 HA proteins have correct antigenic and structural features, and are recognized by B cells and mAbs isolated from seasonally vaccinated humans.ImportanceVaccine development for circulating influenza viruses, particularly for the H3N2 subtype, remains challenging due to consistent antigenic drift. Computationally optimized broadly reactive antigen (COBRA) technology has proven effective for broadening influenza hemagglutinin (HA) elicited antibody responses compared to wild type immunogens. Here we determined the structural features and antigenic profiles of H3 COBRA HA proteins. Two H3 COBRA HA proteins, TJ5 and J4, are better recognized by pre-existing B cells and monoclonal antibodies from the 2017-2018 vaccine season compared to COBRA NG2 and a wild type A/Hong Kong/2014 HA protein. We determined a cryo-EM structure of one mAb that poorly recognizes NG2, mAb TJ5-5, in complex with the TJ5 COBRA HA protein and identified residues critical to mAb recognition. As NG2 is more effective than TJ5 for a recent Hong Kong/2019 virus, these data provide insights into the diminished effectiveness of influenza vaccines across vaccine seasons.
A robust modular automated neuroimaging pipeline for model inputs to TheVirtualBrain
Authors: Frazier-Logue Noah , Wang Justin , Wang Zheng , Sodums Devin , Khosla Anisha , Samson Alexandria , McIntosh Anthony R. , Shen Kelly 
Published: February 2022

AbstractTheVirtualBrain, an open-source platform for large-scale network modelling, can be personalized to an individual using a wide range of neuroimaging modalities. With the growing number and scale of neuroimaging data sharing initiatives of both healthy and clinical populations comes an opportunity to create large and heterogeneous sets of dynamic network models to better understand individual differences in network dynamics and their impact on brain health. Here we present TheVirtualBrain-UK Biobank pipeline, a robust, automated and open-source brain image processing solution to address the expanding scope of TheVirtualBrain project. Our pipeline generates connectome-based modelling inputs compatible for use with TheVirtualBrain. We leverage the existing multimodal MRI processing pipeline from the UK Biobank made for use with a variety of brain imaging modalities. We add various features and changes to the original UK Biobank implementation specifically for informing large-scale network models, including user-defined parcellations for the construction of matching whole-brain functional and structural connectomes. Changes also include detailed reports for quality control of all modalities, a streamlined installation process, modular software packaging, updated software versions, and support for various publicly available datasets. The pipeline has been tested on both healthy and clinical populations and is robust to the morphological changes observed in aging and dementia. In this paper, we describe these and other pipeline additions and modifications in detail, as well as how this pipeline fits into the TheVirtualBrain ecosystem.