bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble P2X7 receptor is elevated in the plasma of COVID-19 patients and correlates with disease severity
Authors: García-Villalba Julio , Hurtado-Navarro Laura , Peñín-Franch Alejandro , Molina-López Cristina , Martínez-Alarcón Laura , Angosto-Bazarra Diego , Baroja-Mazo Alberto , Pelegrín Pablo 
Published: March 2022

AbstractInflammation is a tightly coordinated response against bacterial and viral infections, triggered by the production of pro-inflammatory cytokines. SARS-CoV-2 infection induces COVID-19 disease, characterized by an inflammatory response mediated through the activation of the NLRP3 inflammasome, which results in the production of IL-1β and IL-18 along with pyroptotic cell death. The NLRP3 inflammasome could be also triggered by sterile danger signals such as extracellular ATP triggering the purinergic P2X7 receptor. Severe inflammation in the lungs of SARS-CoV-2 infected individuals is associated with pneumonia, hypoxia and acute respiratory distress syndrome, these being the causes of death associated with COVID-19. Both the P2X7 receptor and NLRP3 have been considered as potential pharmacological targets for treating inflammation in COVID-19. However, there is no experimental evidence of the involvement of the P2X7 receptor during COVID-19 disease. In the present study we determined the concentration of different cytokines and the P2X7 receptor in the plasma of COVID-19 patients and found that along with the increase in IL-6, IL-18 and the IL-1 receptor antagonist in the plasma of COVID-19 patients, there was also an increase in the purinergic P2X7 receptor. Increase in COVID-19 severity and C-reactive protein concentration positively correlated with increased concentration of the P2X7 receptor in the plasma, but not with IL-18 cytokine. The P2X7 receptor was found in the supernatant of human peripheral blood mononuclear cells after inflammasome activation. Therefore, our data suggest that determining levels of the P2X7 receptor in the plasma could be a novel biomarker of COVID-19 severity.
Gain, not concomitant changes in spatial receptive field properties, improves task performance in a neural network attention model
Authors: Fox Kai J , Birman Daniel , Gardner Justin L 
Published: March 2022

AbstractAttention allows us to focus sensory processing on behaviorally relevant aspects of the visual world. One potential mechanism of attention is a change in the gain of sensory responses. However, changing gain at early stages could have multiple downstream consequences for visual processing. Which, if any, of these effects can account for the benefits of attention for detection and discrimination? Using a model of primate visual cortex we document how a Gaussian-shaped gain modulation results in changes to spatial tuning properties. Forcing the model to use only these changes failed to produce any benefit in task performance. Instead, we found that gain alone was both necessary and sufficient to explain category detection and discrimination during attention. Our results show how gain can give rise to changes in receptive fields which are not necessary for enhancing task performance.
Evidence for adaptive morphological plasticity in the Caribbean coral,Acropora cervicornis
Authors: Million Wyatt C. , Ruggeri Maria , O’Donnell Sibelle , Bartels Erich , Krediet Cory J. , Kenkel Carly D. 
Published: March 2022

AbstractGenotype-by-environment interactions (GxE) indicate that variation in organismal traits cannot be explained by fixed effects of genetics or site-specific plastic responses alone. For tropical coral reefs experiencing dramatic environmental change, identifying the contributions of genotype, environment, and GxE on coral performance will be vital for both predicting persistence and developing restoration strategies. We quantified the impacts of G, E, and GxE on the morphology and survival of the endangered coral,A. cervicornis, through an in situ transplant experiment exposing common garden (nursery) raised clones of ten genotypes to nine reef sites in the Florida Keys. By fate-tracking outplants over one year with colony-level 3D photogrammetry, we uncovered significant GxE on coral size and survivorship indicating that no universal winner exists in terms of colony performance. Moreover, the presence of GxE also implies the existence of intraspecific variation in phenotypic plasticity. Rather than differences in mean trait values, we find that individual-level morphological plasticity is adaptive in that the most plastic individuals also exhibited the fastest growth and highest survival. This indicates that adaptive morphological plasticity may continue to evolve, influencing the success ofA. cervicornisand resulting reef communities in a changing climate. As focal reefs are active restoration sites, the knowledge that variation in phenotype is an important predictor of performance can be directly applied to restoration planning. Taken together, these results establishA. cervicornisas a system for studying the eco-evolutionary dynamics of phenotypic plasticity that also can inform genetic- and environment-based strategies for coral restoration.
Evoking the N400 Event-Related Potential (ERP) Component Using a Publicly Available Novel Set of Sentences with Semantically Incongruent or Congruent Eggplants (Endings)
Authors: Toffolo Kathryn K. , Freedman Edward G. , Foxe John J. 
Published: March 2022

AbstractDuring speech comprehension, the ongoing context of a sentence is used to predict sentence outcome by limiting subsequent word likelihood. Neurophysiologically, violations of context-dependent predictions result in amplitude modulations of the N400 event-related potential (ERP) component. While N400 is widely used to measure semantic processing and integration, no publicly-available auditory stimulus set is available to standardize approaches across the field. Here, we developed an auditory stimulus set of 404 sentences that utilized the semantic anomaly paradigm, provided cloze probability for all stimuli, and was developed for both children and adults. With 20 neurotypical adults, we validated that this set elicits robust N400’s, as well as two additional semantically-related ERP components: the late positivity component and the recognition potential. This stimulus set and the 20 high-density (128-channel) electrophysiological datasets are made publicly available here to promote data sharing and reuse. Future studies that use this stimulus set to investigate sentential semantic comprehension in both control and clinical populations may benefit from the increased comparability and reproducibility within this field of research.
Rhythmic firing of neurons in the medulla of conscious freely behaving rats: rhythmic coupling with baroreceptor input
Authors: Kocsis Bernat , Topchiy Irina 
Published: March 2022

AbstractRecent investigations emphasized the importance of neural control of cardiovascular adjustments in complex behaviors, including stress, exercise, arousal, sleep-wake states, and different tasks. Baroreceptor feedback is an essential component of this system acting on different time scales from maintaining stable levels of cardiovascular parameters on the long-term to rapid alterations according to behavior. The baroreceptor input is essentially rhythmic, reflecting periodic fluctuations in arterial blood pressure. Cardiac rhythm is a prominent feature of the autonomic control system, present on different levels, including neuron activity in central circuits. The mechanism of rhythmic entrainment of neuron firing by the baroreceptor input was studied in great detail under anesthesia but recordings of sympathetic-related neuron firing in freely moving animals remain extremely scarce. In this study we recorded multiple single neuron activity in the reticular formation of the medulla in freely moving rats during natural behavior. Neurons firing in synchrony with the cardiac rhythm were detected in each experiment (n=4). In agreement with prior observations in anesthetized cats, we found that neurons in this area exhibited high neuron-to-neuron variability and temporal flexibility in their coupling to cardiac rhythm in freely moving rats, as well. This included firing in bursts at multiples of cardiac cycles, but not directly coupled to the heartbeat, supporting the concept of baroreceptor input entraining intrinsic neural oscillations rather than imposing a rhythm of solely external origin on these networks. It may also point to a mechanism of maintaining the basic characteristics of sympathetic neuron activity, i.e. burst-discharge and cardiac-related rhythmicity, on the background of behavior-related adjustments in their firing rate.
AI-powered pan-species computational pathology: bridging clinic and wildlife care
Authors: AbdulJabbar Khalid , Castillo Simon P. , Hughes Katherine , Davidson Hannah , Boddy Amy M. , Abegglen Lisa M. , Murchison Elizabeth P. , Graham Trevor A. , Spiro Simon , Palmieri Chiara , Yuan Yinyin 
Published: March 2022

AbstractCancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We built the pan-species cancer digital pathology atlas (PANCAD) and conducted the first pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). Furthermore, in 18 other vertebrate species (mammalia=11, reptilia=4, aves=2, and amphibia=1), accuracy (0.57-0.94) was influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. A new metric, named morphospace overlap, was developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on a new understanding of morphological conservation, which could vastly accelerate new developments in veterinary medicine and comparative oncology.
Sex and estrous cycle affect experience-dependent plasticity in mouse primary visual cortex
Authors: Schecter Rachel W. , Jensen Cambria M. , Gavornik Jeffrey P. 
Published: March 2022

AbstractSex hormones can affect cellular physiology and modulate synaptic plasticity, but it is not always clear whether or how sex-dependent differences identifiedin vitroexpress themselves as functional dimorphisms in the brain. Historically, most experimental neuroscience has been conducted using only male animals and the literature is largely mute about whether including female mice in will introduce variability due to inherent sex differences or endogenous estrous cycles. Though this is beginning to change following an NIH directive that sex should be included as a factor in vertebrate research, the lack of information raises practical issues around how to design experimental controls and apply existing knowledge to more heterogeneous populations. Various lines of research suggest that visual processing can be affected by sex and estrous cycle stage. For these reasons, we performed a series ofin vivoelectrophysiological experiments to characterize baseline visual function and experience-dependent plasticity in the primary visual cortex (V1) of male and female mice. We find that sex and estrous stage have no statistically significant effect on baseline acuity measurements, but that both sex and estrous stage have can modulate two mechanistically distinct forms of experience dependent cortical plasticity. We also demonstrate that resulting variability can be largely controlled with appropriate normalizations. These findings suggest that V1 plasticity can be used for mechanistic studies focusing on how sex hormones effect experience dependent plasticity in the mammalian cortex.
Goal-specific brain MRI harmonization
Authors: An Lijun , Chen Jianzhong , Chen Pansheng , Zhang Chen , He Tong , Chen Christopher , Zhou Juan Helen , Yeo B.T. Thomas ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Australian Imaging Biomarkers and Lifestyle Study of Aging
Published: March 2022

AbstractThere is significant interest in pooling magnetic resonance image (MRI) data from multiple datasets to enable mega-analysis. Harmonization is typically performed to reduce heterogeneity when pooling MRI data across datasets. Most MRI harmonization algorithms do not explicitly consider downstream application performance during harmonization. However, the choice of downstream application might influence what might be considered as study-specific confounds. Therefore, ignoring downstream applications during harmonization might potentially limit downstream performance. Here we propose a goal-specific harmonization framework that utilizes downstream application performance to regularize the harmonization procedure. Our framework can be integrated with a wide variety of harmonization models based on deep neural networks, such as the recently proposed conditional variational autoencoder (cVAE) harmonization model. Three datasets from three different continents with a total of 2787 participants and 10085 anatomical T1 scans were used for evaluation. We found that cVAE removed more dataset differences than the widely used ComBat model, but at the expense of removing desirable biological information as measured by downstream prediction of mini mental state examination (MMSE) scores and clinical diagnoses. On the other hand, our goal-specific cVAE (gcVAE) was able to remove as much dataset differences as cVAE, while improving downstream cross-sectional prediction of MMSE scores and clinical diagnoses.
Emergence of hyper insecticide-resistant dengue vectors in Indochina Peninsula: threats of concomitant knockdown resistance mutations
Authors: Kasai Shinji , Itokawa Kentaro , Uemura Nozomi , Takaoka Aki , Furutani Shogo , Maekawa Yoshihide , Kobayashi Daisuke , Imanishi-Kobayashi Nozomi , Amoa-Bosompem Michael , Murota Katsunori , Higa Yukiko , Kawada Hitoshi , Minakawa Noboru , Cuong Tran Chi , Yen Nguyen Thi , Phong Tran Vu , Keo Sath , Kang Kroesna , Miura Kozue , Ng Lee Ching , Teng Hwa-Jen , Dadzie Samuel , Subekti Sri , Mulyatno Kris Cahyo , Sawabe Kyoko , Tomita Takashi , Komagata Osamu 
Published: March 2022

AbstractAedes aegypti(Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. Nevertheless, the development of pyrethroid resistance is a major obstacle to mosquito/disease control worldwide. Here, we focused on the mutations in the target site of pyrethroid insecticides, voltage-sensitive sodium channel (Vssc), and found thatAe. aegypticollected from Vietnam has the L982W allele in theVsscat a high frequency (>79%). L982W mutation is located in the highly conserved region ofVsscthat is associated with sodium–ion selectivity and permeation rate. Strains having the L982W allele showed similar or even higher levels of resistance to pyrethroids than those having V1016G, a typical knockdown resistance allele in Asia. Furthermore, concomitant mutations L982W+F1534C and V1016G+F1534C were confirmed, and strains having these multipleVsscmutations exhibited incomparably higher levels of pyrethroid resistance than any other field population ever reported. Molecular modeling analysis confirmed that these concomitant mutant alleles could interfere with approaching pyrethroid toVssc. Remarkably, >90% ofVsscofAe. aegyptiwere occupied by these hyper insecticide-resistant haplotypes in Phnom Penh city, Cambodia. Analysis of wholeVssccoding genes suggested thatVsscs have evolved into stronger resistant forms efficiently through gene recombination events. At this point, L982W has never been detected inVsscofAe. aegyptifrom any other neighboring countries. We strongly emphasize the need to be vigilant about these strong resistance genes spreading to the world through Indochina Peninsula.Significance StatementThe high frequency (>78%) of the L982W allele was detected at the target site of the pyrethroid insecticide, the voltage-sensitive sodium channel (Vssc) ofAedes aegypticollected from Vietnam and Cambodia. Haplotypes having concomitant mutations L982W+F1534C and V1016G+F1534C were also confirmed in both countries, and their frequency was high (>90%) in Phnom Penh, Cambodia. Strains having these haplotypes exhibited substantially higher levels of pyrethroid resistance than any other field population ever reported. The L982W mutation has never been detected in any country of the Indochina Peninsula except Vietnam and Cambodia, but it may be spreading to other areas of Asia, which can cause an unprecedentedly serious threat to the control of dengue fever as well as otherAedes-borne infectious diseases.
Soft disorder modulates the assembly path of protein complexes
Authors: Seoane Beatriz , Carbone Alessandra 
Published: March 2022

AbstractThe relationship between interactions, flexibility and disorder in proteins has been explored from many angles over the years: folding upon binding, flexibility of the core relative to the periphery, entropy changes, etc. In this work, we provide statistical evidence for the involvement of highly mobile and disordered regions in complex assembly. We ordered the entire set of X-ray crystallographic structures in the Protein Data Bank into hierarchies of progressive interactions involving identical or very similar protein chains, yielding 40205 hierarchies of protein complexes with increasing numbers of partners. We then examine them as proxies for the assembly pathways. Using this database, we show that upon oligomerisation, the new interfaces tend to be observed at residues that were characterised as softly disordered (flexible, amorphous or missing residues) in the complexes preceding them in the hierarchy. We also rule out the possibility that this correlation is just a surface effect by restricting the analysis to residues on the surface of the complexes. Interestingly, we find that the location of soft disordered residues in the sequence changes as the number of partners increases. Our results show that there is a general mechanism for protein assembly that involves soft disorder and modulates the way protein complexes are assembled. This work highlights the difficulty of predicting the structure of large protein complexes from sequence and emphasises the importance of linking predictors of soft disorder to the next generation of predictors of complex structure. Finally, we investigate the relationship between the Alphafold2’s confidence metric pLDDT for structure prediction in unbound versus bound structures, and soft disorder. We show a strong correlation between Alphafold2 low confidence residues and the union of all regions of soft disorder observed in the hierarchy. This paves the way for using the pLDDT metric as a proxy for predicting interfaces and assembly paths.AvailabilityAll the data used for these analyses (hierarchies of interactions and soft disorder) are available at the websitehttp://www.lcqb.upmc.fr/softdisorder-assembly/.Author summaryBoth flexibility and intrinsic disorder are used as regulatory mechanisms in proteins. They can alter the spatial positions of important recognition sites, and increased mobility appears to facilitate ligand binding through conformational selection. In this work, we show statistical evidence that soft disorder is directly involved in the process of protein assembly and that migration of soft disorder after binding gives rise to new or altered functions in the protein complex. Given the impressive progress that AlphaFold2 has made in protein structure prediction in recent years, this work highlights the importance of also correctly predicting conformational heterogeneity, mobility and intrinsic disorder in order to access the full functional repertoire and interaction network of a given protein.
Pudendal, but not tibial, nerve stimulation modulates vulvar blood perfusion in anesthetized rodents
Authors: Bottorff Elizabeth C. , Bruns Tim M. 
Published: March 2022

AbstractIntroduction and HypothesisPreclinical studies have shown that neuromodulation can increase vaginal blood perfusion, but the effect on vulvar blood perfusion is unknown. We hypothesized that pudendal and tibial nerve stimulation could evoke an increase in vulvar blood perfusion.MethodsWe used female Sprague-Dawley rats for non-survival procedures under urethane anesthesia. We measured perineal blood perfusion in response to twenty-minute periods of pudendal and tibial nerve stimulation using laser speckle contrast imaging (LSCI). After a thoracic-level spinalization and a rest period, we repeated each stimulation trial. We calculated average blood perfusion before, during, and after stimulation for three perineal regions (vulva, anus, and inner thigh), for each nerve target and spinal cord condition.ResultsWe observed a significant increase in vulvar, anal, and inner thigh blood perfusion during pudendal nerve stimulation in spinally intact and spinalized rats. Tibial nerve stimulation had no effect on perineal blood perfusion for both spinally intact and spinalized rats.ConclusionsThis is the first study to examine vulvar hemodynamics with LSCI in response to nerve stimulation. This study demonstrates that pudendal nerve stimulation modulates vulvar blood perfusion, indicating the potential of pudendal neuromodulation to improve genital blood flow as a treatment for women with sexual dysfunction. This study provides further support for neuromodulation as a treatment for women with sexual arousal disorders. Studies in unanesthetized animal models with genital arousal disorders are needed to obtain further insights into the mechanisms of neural control over genital hemodynamics.Brief SummaryIn an anesthetized rodent model, electrical stimulation of the pudendal nerve will drive increases in vulvar blood perfusion while tibial nerve stimulation will not.
Engineering of Sr33 and Sr50 plant immune receptors to alter recognition specificity and autoactivity
Authors: Tamborski Janina , Seong Kyungyong , Liu Furong , Staskawicz Brian , Krasileva Ksenia V 
Published: March 2022

AbstractPlants possess cytoplasmic immune receptors called nucleotide-binding leucine-rich repeat receptors (NLRs) that recognize the presence of a pathogen through a range of mechanisms: direct binding of effectors or indirect recognition of effector actions. The direct binding of effectors has been shown to be mediated through the NLR’s leucine-rich repeat (LRR) domain. Accurate prediction of amino acids involved in these direct interactions can greatly enhance understanding of effector recognition and inform efforts to engineer new resistance. In this study, we utilized two homologous NLR resistance genes from wheat, Sr33 and Sr50, that recognize distinct effectors by directly binding to them through their LRR domain. While the effector recognized by Sr50 is known and described as AvrSr50, the effector recognized by Sr33 remains unknown. Through a combination of phylogenetics, allele diversity analysis in the LRR and structural modeling, we identified the amino acids in Sr50 likely to physically interact with its effector. Mutation of these sites helped identify 12 amino acids we hypothesized to be sufficient to mediate effector binding in Sr50. Changing these 12 corresponding amino acids in Sr33, we showed AvrSr50-dependent initiation of cell death in wheat protoplasts and Nicotiana benthamiana. Furthermore, we were able to pinpoint and change amino acid residues that govern autoactivity of Sr50 in the wheat protoplast cell death assay. These findings are a major advance towards the successful engineering of new effector recognition specificities in direct binder NLRs.