bluuebunny/crossref_metadata_2025_split huggingface dataset:
A class of secreted mammalian peptides with potential to expand cell-cell communication
Authors: Wiggenhorn Amanda L. , Abuzaid Hind Z. , Coassolo Laetitia , Li Veronica L. , Tanzo Julia T. , Wei Wei , Lyu Xuchao , Svensson Katrin J. , Long Jonathan Z. 
Published: June 2023

SummaryPeptide hormones and neuropeptides are fundamental signaling molecules that control diverse aspects of mammalian homeostasis and physiology. Here we demonstrate the endogenous presence of a sequence diverse class of orphan, blood-borne peptides that we call “capped peptides.” Capped peptides are fragments of secreted proteins and defined by the presence of two post-translational modifications – N-terminal pyroglutamylation and C-terminal amidation – which function as chemical “caps” of the intervening sequence. Capped peptides share many regulatory characteristics in common with that of other signaling peptides, including dynamic regulation in blood plasma by diverse environmental and physiologic stimuli. One capped peptide, CAP-TAC1, is a tachykinin neuropeptide-like molecule and a nanomolar agonist of multiple mammalian tachykinin receptors. A second capped peptide, CAP-GDF15, is a 12-mer peptide that reduces food intake and body weight. Capped peptides therefore define a largely unexplored class of circulating molecules with potential to regulate cell-cell communication in mammalian physiology.
22kHz Ultrasonic Vocalizations and Body Freezing May Represent Two Systems of Fear in Rodent Fear Conditioning Paradigms
Authors: Zheng Benhuiyuan , Bao Lili , Yu Delin , Yin Bin 
Published: June 2023

SummaryThe “two-system” framework of fear proposed by LeDoux and Pine (2016) sparked a discussion on the understanding of fear, prompting a reevaluation of rodent fear conditioning studies. We propose that 22kHz ultrasonic vocalizations (USV) may symbolize the subjective negative emotional states in rats. To evaluate this, we designed a series of fear conditioning experiments with varied parameters, comparing the expression of 22kHz USV and body freezing – a traditional fear index. These expressions were further assessed in fear generalization tests. Our findings suggest a distinct separation between body freezing and 22kHz vocalizations in fear conditioning under different conditions. The results indicate that 22kHz USV may more accurately signify the subjective state of fear, whereas body freezing may denote an automatic defensive response in rats. Consequently, we posit that the two-system fear framework may extend to rodent fear conditioning paradigms. Therefore, researchers should place greater emphasis on 22kHz vocalizations when investigating the subjective state of fear.
Practice often and always get ready: a spiking mechanistic model for voluntary motor control
Authors: Zhao Chen , Cui He 
Published: June 2023

AbstractIn many voluntary movement, neural activities ranging from cortex to spinal cord can be roughly described as the stages of motor intention, preparation, and execution. Recent advances in neuroscience have proposed many theories to understand how motor intention can be transformed into action following these stages, but they still lack a holistic and mechanistic theory to account for the whole process. Here, we try to formulate this question by abstracting two underlying principles: 1) the neural system is specializing the final motor command through a hierarchical network by multitudes of training supervised by the action feedback (“practice often”); 2) prediction is a general mechanism throughout the whole process by providing feedback control for each local layer (“always get ready”). Here we present a theoretical model to regularize voluntary motor control based on these two principles. The model features hierarchical organization and is composed of spiking building blocks based on the previous work in predictive coding and adaptive control theory. By simulating our manual interception paradigm, we show that the network could demonstrate motor preparation and execution, generate desired output trajectory following intention inputs, and exhibit comparable cortical and endpoint dynamics with the empirical data.
Investigating Clot-flow Interactions by Integrating Intravital Imaging with In Silico Modeling for Analysis of Flow, Transport, and Hemodynamic Forces
Authors: Teeraratkul Chayut , Tomaiuolo Maurizio , Stalker Timothy J. , Mukherjee Debanjan 
Published: June 2023

AbstractAs a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unifiedin silicoframework to quantify the dynamic clot-flow interactions. We outline the development of the methodology referred to as Intravital Integrated In Silico Modeling orIVISim, and then demonstrate the method on a sample set of simulations comprising clot formation following laser injury in two mouse cremaster arteriole injury model data: one wild-type mouse case, and one diYF knockout mouse case. Simulation predictions are verified against experimental observations of transport of caged fluorescent Albumin (cAlb) in both models. Through these simulations, we illustrate how theIVISimmethodology can provide insights into hemostatic processes, the role of flow and clot-flow interactions, and enable further investigations comparing and contrasting different biological model scenarios and parameter variations.
Oxygen loss compromises the survival and cognition of a coastal cephalopod
Authors: Court Mélanie , Macau Marta , Ranucci Maddalena , Repolho Tiago , Lopes Vanessa Madeira , Rosa Rui , Paula José Ricardo 
Published: June 2023

AbstractThe ocean is undergoing deoxygenation and the spread of hypoxic areas. Ocean deoxygenation and standing levels of hypoxia are shrinking fundamental niches, particularly in coastal areas, yet documented repercussions on species development and behavior are limited. Here, we tackled the impacts of deoxygenation (7 mg O2 L-1), mild hypoxia (nocturnal 5 mg O2 L-1), and severe hypoxia (2 mg O2 L-1) on cuttlefish (Sepia officinalis) development (hatching success, development time, mantle length) and behavior, i.e., ability to learn (associative-and socially), to camouflage, and to explore its surroundings spatially. We found that hypoxia yielded lower survival rates, smaller body sizes and inhibited predatory (increased latency to attack the prey) and anti-predator (camouflage) behaviors. Acute and chronic exposure to low oxygen produced similar effects on cognition (inability to socially learn, increased open-field activity levels, no changes in thigmotaxis). It is thus expected that, although cuttlefish can withstand oxygen limitation to a certain degree, expanding hypoxic zones will diminish current habitat suitability.
Early Alzheimer’s disease pathology in human cortex is associated with a transient phase of distinct cell states
Authors: Gazestani Vahid , Kamath Tushar , Nadaf Naeem M. , Burris SJ , Rooney Brendan , Junkkari Antti , Vanderburg Charles , Rauramaa Tuomas , Therrien Martine , Tegtmeyer Matthew , Herukka Sanna-Kaisa , Abdulraouf Abdulraouf , Marsh Samuel , Malm Tarja , Hiltunen Mikko , Nehme Ralda , Stevens Beth , Leinonen Ville , Macosko Evan Z. 
Published: June 2023

SummaryCellular perturbations underlying Alzheimer’s disease are primarily studied in human postmortem samples and model organisms. Here we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of Alzheimer’s disease pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes–which we refer to as the Early Cortical Amyloid Response—were prominent in neurons, wherein we identified a transient state of hyperactivity preceding loss of excitatory neurons, which correlated with the selective loss of layer 1 inhibitory neurons. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathological burden increased. Lastly, both oligodendrocytes and pyramidal neurons upregulated genes associated with amyloid beta production and processing during this early hyperactive phase. Our integrative analysis provides an organizing framework for targeting circuit dysfunction, neuroinflammation, and amyloid production early in AD pathogenesis.
Comparative Brain-Wide Mapping of Ketamine and Isoflurane-Activated Nuclei and Functional Networks
Authors: Hu Yue , Du Wenjie , Qi Jiangtao , Luo Huoqing , Zhang Zhao , Luo Mengqiang , Wang Yingwei 
Published: June 2023

AbstractKetamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher-order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.
Subcutaneous and orally self-administered high-dose carprofen in male and female mice: pharmacokinetics, tolerability and impact on cage-side pain indicators
Authors: Glasenapp Aylina , Bankstahl Jens P. , Bähre Heike , Glage Silke , Bankstahl Marion 
Published: June 2023

AbstractSurgical interventions in mice are prerequisite in various research fields and require appropriate pain relief, not only to ensure animal welfare but also to avoid influence of pain on research findings. Carprofen is a non-steroidal anti-inflammatory drug that is commonly used as an analgesic for interventions inducing mild to moderate pain in animals. Despite its frequent use also in laboratory rodents, data on pharmacokinetics and side effects, and on its potential impact on behavioral pain indicators are rare.This study aimed to determine pharmacokinetic and tolerability profiles of high dose carprofen in male and female C57Bl/6J mice, administered via single subcutaneous injection (s.c.) and oral self-administration per drinking water (d.w.). Plasma concentrations of carprofen were measured at various time points, and side effects were evaluated using a modified Irwin test protocol, hematology and histopathology. Additionally, potential effects on behavioral pain indicators commonly used to assess post-surgical pain, such as the mouse grimace scale, wheel running activity, burrowing, nesting and grooming behavior were investigated.Quantification of carprofen in plasma revealed maximum plasma concentrations of 133.4 ± 11.3 µg/ml after 1 hour and an elimination half-life of 8.52 hour after single s.c. injection of 20 mg/kg carprofen. Oral self-administration of carprofen (25 mg/kg/24 h) resulted in a steady-state < 24 hours over 5 days after treatment start with plasma levels of around 60 µg/ml. The carprofen-medicated water was highly accepted, and increased d.w. intake was observed in the first 24 hours after exposure for both sexes (p < 0.0001). Irwin test detected only minor side effects, and hematology and histopathology where without pathological findings that could be attributed to carprofen treatment. Except for a decrease of 49-70 % in wheel running activity in male mice, behavioral pain indicators were only very mildly affected.This study determined carprofen plasma levels in mice lying well above an estimated therapeutic concentration for both routes of administration. Carprofen was well tolerated at recommended high doses and may provide sufficient analgesia for minor interventions as well as be applied as a tolerable component in multimodal analgesic regimens.
miniBUSCO: a faster and more accurate reimplementation of BUSCO
Authors: Huang Neng , Li Heng 
Published: June 2023

AbstractMotivationAssembly completeness evaluation of genome assembly is a critical assessment of the accuracy and reliability of genomic data. An incomplete assembly can lead to errors in gene predictions, annotation, and other downstream analyses. BUSCO is one of the most widely used tools for assessing the completeness of genome assembly by comparing the presence of a set of single-copy orthologs conserved across a wide range of taxa. However, the runtime of BUSCO can be long, particularly for some large genome assemblies. It is a challenge for researchers to quickly iterate the genome assemblies or analyze a large number of assemblies.ResultsHere, we present miniBUSCO, an efficient tool for assessing the completeness of genome assemblies. miniBUSCO utilizes the protein-to-genome aligner miniprot and the datasets of conserved orthologous genes from BUSCO. Our evaluation of the real human assembly indicates that miniBUSCO achieves a 14-fold speedup over BUSCO. Furthermore, miniBUSCO reports a more accurate completeness of 99.6% than BUSCO’s completeness of 95.7%, which is in close agreement with the annotation completeness of 99.5% for T2T-CHM13.Availabilityhttps://github.com/huangnengCSU/minibusco.Contacthli@ds.dfci.harvard.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Improving risk communication: a pilot randomised-control trial assessing the impact of visual aids for interventional consent
Authors: Chatzopoulou Despoina , Jalal Arif Hanafi Bin , Stoyanov Danail , Marcus Hani J , Pandit Anand S 
Published: June 2023

AbstractIntroductionInformed consent is a fundamental component in the work-up for surgical procedures. Our study aims to assess the impact of visual tools in the informed consent process of a common medical and neurosurgical procedure: a lumbar puncture.MethodsParticipants were healthy adults without any underlying cognitive impairment, and they were randomized to complete a questionnaire containing either the control video or intervention video. Both videos contained identical audio narration, however the intervention video included additional visual aids such as anatomical diagrams, icon arrays and Paling scales. Outcome measure included knowledge of the procedure (including recall of numerical risks), 5-point Likert scale questions, usability as measured by the System Usability Scale, acceptability as measured by the Acceptability of Intervention Measure and appropriateness as measured by the Intervention Appropriateness Measure.ResultsIn total, 52 participants were randomized to the control (n = 25) or intervention (n=27) group. There was no statistical difference in numerical risk recall, understanding of the procedure or its benefits. The intervention group reported better understanding of the risks (p = 0.05), felt they could more easily better explain the risks to others (p = 0.01), and felt less overwhelmed with information (p = 0.03). The intervention group was also rated as more acceptable (p = 0.02).ConclusionOur pilot study tentatively demonstrates that visual risk communication adjuncts offer several advantages over traditionally obtained surgical consent without being inferior in understanding of the procedure or recall of numerical risks.
Olfactory cortex output pathways exhibit robust differences in their ability to drive learned aversion
Authors: Vieira Inês , Bryzgalov Dmitri 
Published: June 2023

AbstractThe olfactory (piriform) cortex contains a large diversity of neural cell types, defined by their molecular identity, morphology, functional properties and projection target specificity. How these distinct neural cell types contribute to the control of olfactory-driven behaviors remains unknown. Here, we use a behavioral task in which optogenetic activation of subpopulations of piriform neurons is associated with an unconditioned aversive stimulus. We find that piriform neurons projecting to the olfactory bulb or the medial prefrontal cortex efficiently drive a learned escape behavior. In contrast, neurons projecting to the cortical amygdala or the lateral entorhinal cortex failed to support a behavioral response. Our results suggest that different piriform neural subnetworks exhibit robust differences in their ability to relate neural activity to behavioral output.
Prevalence and Risk factors of Urinary Schistosomiasis in Kaporo Village, Karonga District, Malawi
Authors: Nyondo Christopher S. , Mthawanji Rhosheen , Chisale Master 
Published: June 2023

AbstractObjectiveThe aim of the study was to determine the prevalence and Risk factors of urogenital schistosomiasis in Karonga district; it also sought to determine the relationship between involvement in MDA advocacy campaigns and Knowledge level of the disease.MethodsThe study enrolled 251 participants that responded to the questionnaire-guided interview and submitted urine for microscopy.ResultsOf 251 children that were enrolled 87 (34.7%) were found to haveS.haematobiumeggs. Chi-square analysis established that having a parent in rice farming (p=0.029) occupation is a key risk factor for urogenital schistosomiasis. It was also surprising to note that those schoolchildren who received Praziquantel during MDA had significantly higher prevalence (p=0.010). Furthermore, this study revealed that they is no association between a child involving in MDA advocacy compaigns and level of knowledge on schistosomiasis transmission.
A prospective, single-center, randomized phase 2 trial of etoposide in severe COVID-19
Authors: Halpin Meredith , Lerner Adam , Sagar Manish , Govender Praveen , Shah Bhavesh , Weinberg Janice , Sarosiek Shayna , Sloan J. Mark 
Published: June 2023

AbstractThe systemic inflammatory response seen in patients with severe COVID-19 shares many similarities with the changes observed in hemophagocytic lymphohistiocytosis (HLH); a disease characterized by excessive immune activation. Many patients with severe COVID qualify for a diagnosis of HLH. Etoposide, an inhibitor of topoisomerase II is used to control inflammation in HLH. This randomized, open-label, single center phase II trial attempted to determine whether etoposide can be used to blunt the inflammatory response in severe COVID. This trial was closed early after eight patients were randomized. This underpowered trial did not meet its primary endpoint of improvement in pulmonary status by two categories on an 8 point ordinal scale of respiratory function. There were not significant differences in secondary outcomes including overall survival at 30 days, cumulative incidence of grade 2 through 4 adverse events during hospitalization, duration of hospitalization, duration of ventilation and improvement in oxygenation or paO2/FIO2 ratio or improvement in inflammatory markers associated with cytokine storm. A high rate of grade 3 myelosuppression was noted in this critically ill population despite dose reduction, a toxicity which will limit future attempts to explore the utility of etoposide for virally-driven cytokine storm or HLH.
Association of alpha-aminoadipic acid (2-AAA) with cardiometabolic risk factors in healthy and high-risk individuals
Authors: Desine Stacy , Gabriel Curtis L. , Smith Holly M. , Antonetti Olivia R. , Wang Chuan , Calcutt M. Wade , Doran Amanda C. , Silver Heidi J. , Nair Sangeeta , Terry James G. , Carr J. Jeffrey , Linton MacRae F. , Brown Jonathan D. , Koethe John R. , Ferguson Jane F. 
Published: June 2023

ABSTRACTPlasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.