bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropathic injury drives a generalized negative affective state in mice
Authors: Norris Makenzie R. , Bilbily John , Becker Léa J. , Borges Gustavo , Chang Yu-Hsuan , Dunn Samantha S. , Madasu Manish K. , Al-Hasani Ream , Creed Meaghan C. , McCall Jordan G. 
Published: November 2022

AbstractNeuropathic pain causes both sensory and emotional maladaptation. Preclinical animal studies of neuropathic pain-induced negative affect could result in novel insights into the mechanisms of chronic pain. Modeling pain-induced negative affect, however, is variable across research groups and conditions. The same injury may or may not produce robust negative affective behavioral responses across different species, strains, and laboratories. Here we sought to identify negative affective consequences of the spared nerve injury model on C57BL/6J male and female mice. We found no significant effect of spared nerve injury across a variety of approach-avoidance, hedonic choice, and coping strategy assays. We hypothesized these inconsistencies may stem in part from the short test duration of these assays. To test this hypothesis, we used the homecage-based Feeding Experimentation Device version 3 to conduct 12-hour, overnight progressive ratio testing to determine whether mice with chronic spared nerve injury had decreased motivation to earn palatable food rewards. Our data demonstrate that despite equivalent task learning, spared nerve injury mice are less motivated to work for a sugar pellet than sham controls. Further, when we normalized behavioral responses across all the behavioral assays we tested, we found that a combined normalized behavioral score is predictive of injury-state and significantly correlates with mechanical thresholds. Together these results suggest that homecage-based operant behaviors provide a useful platform for modeling nerve injury-induced negative affect and that valuable pain-related information can arise from agglomerative data analyses across behavioral assays - even when individual inferential statistics do not demonstrate significant mean differences.
Converting an allocentric goal into an egocentric steering signal
Authors: Pires Peter Mussells , Abbott L.F. , Maimon Gaby 
Published: November 2022

AbstractNeuronal signals relevant for spatial navigation have been described in many species1–12, however, a circuit-level understanding of how such signals interact to guide behaviour is lacking. Here we characterize a neuronal circuit in theDrosophilacentral complex that compares internally generated estimates of the fly’s heading and goal angles––both encoded in world-centred, or allocentric, coordinates––to generate a body-centred, or egocentric, steering signal. Past work has argued that the activity of EPG cells, or “compass neurons”2, represents the fly’s moment-to-moment angular orientation, orheading angle, during navigation13. An animal’s moment-to-moment heading angle, however, is not always aligned with itsgoal angle, i.e., the allocentric direction in which it wishes to progress forward. We describe a second set of neurons in theDrosophilabrain, FC2 cells14, with activity that correlates with the fly’s goal angle. Furthermore, focal optogenetic activation of FC2 neurons induces flies to orient along experimenter-defined directions as they walk forward. EPG and FC2 cells connect monosynaptically to a third neuronal class, PFL3 cells14,15. We found that individual PFL3 cells show conjunctive, spike-rate tuning to both heading and goal angles during goal-directed navigation. Informed by the anatomy and physiology of these three cell classes, we develop a formal model for how this circuit can compare allocentric heading- and goal-angles to build an egocentric steering signal in the PFL3 output terminals. Quantitative analyses and optogenetic manipulations of PFL3 activity support the model. The biological circuit described here reveals how two, population-level, allocentric signals are compared in the brain to produce an egocentric output signal appropriate for the motor system.
Recombinant protein delivery enables modulation of the phototransduction cascade in mouse retina
Authors: Asteriti Sabrina , Marino Valerio , Avesani Anna , Biasi Amedeo , Dal Cortivo Giuditta , Cangiano Lorenzo , Dell’Orco Daniele 
Published: November 2022

AbstractRetinal dystrophies of genetic origin are often associated with mutations in the genes involved in the phototransduction cascade in photoreceptors, a paradigmatic signaling pathway mediated by G protein-coupled receptors. Photoreceptor viability is strictly dependent on the levels of the second messengers cGMP and Ca2+. Here we explored the possibility of modulating the phototransduction cascade in mouse rods using direct or liposome-mediated administration of a recombinant protein crucial for regulating the interplay of the second messengers in photoreceptor outer segments. The effects of administration of the free and liposome-encapsulated human guanylate cyclase-activating protein (GCAP1) were compared in biological systems of increasing complexity (in cyto, ex vivo, andin vivo).Analysis of protein biodistribution and direct measurement of functional alteration in rod photoresponses show that the exogenous GCAP1 protein is fully incorporated into the mouse retina and photoreceptor outer segments. Furthermore, only in the presence of a point mutation associated with cone-rod dystrophy in humans p.(E111V), protein delivery induces a disease-like electrophysiological phenotype, consistent with constitutive activation of the retinal guanylate cyclase. Our study demonstrates that both direct and liposome-mediated protein delivery are powerful tools for targeting signaling cascades in neuronal cells, which could be particularly important for the treatment of autosomal dominant genetic diseases.
Optical opening of the blood brain barrier for targeted and ultra-sparse viral infection of cells in the mouse cortex
Authors: Reeson Patrick L. , Boghozian Roobina , Cote Ana-Paula , Brown Craig E. 
Published: November 2022

AbstractAdeno-associated viruses (AAVs) are used in a wide array of experimental situations for driving expression of biosensors, recombinases and opto/chemo-genetic actuators in the brain. However, conventional approaches for minimally invasive, spatially precise and ultra-sparse AAV mediated transduction of cells during imaging experiments, has remained a significant challenge. Here we show that intravenous injection of commercially available AAVs at different doses, combined with laser based perforation of single cortical capillaries through a cranial widow, allows for ultra-sparse, titrate-able, and micron level precision for delivery of viral vectors with relatively little inflammation or tissue damage. Further, we show the utility of this approach for eliciting sparse expression of GCaMP6, channel-rhodopsin or fluorescent reporters in neurons and astrocytes within specific functional domains in normal and stroke damaged cortex. This technique represents a facile approach for targeted delivery of viral vectors that should assist in the study of cell types and circuits in the cerebral cortex.
Unplanned readmission to hospital and its predictors in heart failure patients, Ethiopia: a retrospective cohort study
Authors: Ayenew Birhanu , Kumar Prem , Hussein Adem 
Published: November 2022

AbstractBackgroundThe burden of heart failure increases over time and is a leading cause of unplanned readmissions worldwide. In addition, its impact has doubled in countries with limited health resources, including Ethiopia. Identifying and preventing the possible contributing factors is crucial to reduce unplanned hospital readmission and to improve clinical outcomes.MethodA hospital-based retrospective cohort study design was employed from January 1, 2016, to December 30, 2020. The data was collected from 572 randomly selected medical records using data extraction checklists. Data were entered in Epi-data version 4.6 and analyzed with Stata version 17. The Kaplan-Meier and log-rank tests were used to estimate and compare the survival failure time. A Cox proportional hazard analysis was computed to identify predictors of readmission. Finally, the statistical significance level was declared at a p-value <0.05 with an adjusted odds ratio and a 95% confidence interval.ResultIn this study, a total of 151 (26.40%) heart failure patients were readmitted within 30 days of discharge. In the multivariate cox proportional hazards analysis being an age (>65 years) (AHR: 3.172, 95%CI:.21, 4.55), rural in residency (AHR: 2.47, 95%CI: 1.44, 4.24), Asthma/COPD (AHR: 1.62, 95%CI: 1.11, 2.35), HIV/AIDS (AHR: 1.84, 95%CI: 1.24, 2.75), Haemoglobin level 8-10.9 g/dL (AHR: 6.20, 95%CI: 3.74, 10.28), and Mean platelet volume >9.1fl (AHR: 2.08, 95%CI: 1.27, 3.40) were identified as independent predictors of unplanned hospital readmission.ConclusionThe incidence of unplanned hospital readmission was relatively high among heart failure patients. Elderly patients, rural residency, comorbidity, higher mean platelet volume, and low hemoglobin level were independent predictors of readmission. Therefore, working on these factors will help to reduce the hazard of unplanned hospital readmission.
Quantifying Evoked Responses through Information-Theoretical Measures
Authors: Fuhrer Julian , Glette Kyrre , Llorens Anaïs , Endestad Tor , Solbakk Anne-Kristin , Blenkmann Alejandro 
Published: November 2022

AbstractInformation theory is a viable candidate to advance our understanding of how the brain processes information generated in the internal or external environment. With its universal applicability, information theory enables the analysis of complex data sets, is free of requirements about the data structure, and can help infer the underlying brain mechanisms. Information-theoretical metrics such as Entropy or Mutual Information have been highly beneficial for analyzing neurophysiological recordings. However, a direct comparison of the performance of these methods with well-established metrics, such as the t-test, is rare. Here, such a comparison is carried out by evaluating the novel method of Encoded Information with Mutual Information, Gaussian Copula Mutual Information, Neural Frequency Tagging, and t-test. We do so by applying each method to event-related potentials and event-related activity in different frequency bands originating from intracranial electroencephalography recordings of humans and marmoset monkeys. Encoded Information is a novel procedure that assesses the similarity of brain responses across experimental conditions by compressing the respective signals. Such an information-based encoding is attractive whenever one is interested in detecting where in the brain condition effects are present.
Mutation-Guided Vaccine Design: A Strategy for Developing Boosting Immunogens for HIV Broadly Neutralizing Antibody Induction
Authors: Wiehe Kevin , Saunders Kevin O. , Stalls Victoria , Cain Derek W. , Venkatayogi Sravani , Martin Beem Joshua S. , Berry Madison , Evangelous Tyler , Henderson Rory , Hora Bhavna , Xia Shi-Mao , Jiang Chuancang , Newman Amanda , Bowman Cindy , Lu Xiaozhi , Bryan Mary E. , Bal Joena , Sanzone Aja , Chen Haiyan , Eaton Amanda , Tomai Mark A. , Fox Christopher B. , Tam Ying , Barbosa Christopher , Bonsignori Mattia , Muramatsu Hiromi , Alam S. Munir , Montefiori David , Williams Wilton B. , Pardi Norbert , Tian Ming , Weissman Drew , Alt Frederick W. , Acharya Priyamvada , Haynes Barton F. 
Published: November 2022

AbstractA major goal of HIV-1 vaccine development is induction of broadly neutralizing antibodies (bnAbs). While success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knock-in mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof-of concept and milestone towards development of an HIV vaccine.One-Sentence SummaryA vaccine strategy for selecting key rare antibody mutations is shown to induce HIV broadly neutralizing antibodies in mice.
Some like it hotter: differential thermal preferences among lizard color morphs
Authors: Thompson Asher , Kapsanaki Vassiliki , Liwanag Heather E. M. , Pafilis Panayiotis , Wang Ian J. , Brock Kinsey M. 
Published: November 2022

ABSTRACTTemperature rules the lives of ectotherms. To perform basic biological functions, ectotherms must make behavioral adjustments to keep their body temperatures near a preferred temperature (Tpref). Many color polymorphic lizards are active thermoregulators and exhibit morph differences in traits related to thermoregulation, such as color, body size, and microhabitat use. The Aegean wall lizard,Podarcis erhardii, is a heliothermic lizard with orange, white, and yellow color morphs that differ in size, behavior, and microhabitat use. Here, we tested whetherP. erhardiicolor morphs from the same population from Naxos island, Greece, differ in Tpref. We hypothesized that orange morphs would prefer lower temperatures than white and yellow morphs because orange morphs are often found on cooler substrates and in microhabitats with more vegetation cover. We obtained Tpref for 95 individuals using laboratory thermal gradient experiments of wild-caught lizards and found that orange morphs do, indeed, prefer significantly cooler temperatures, regardless of body size differences. Average orange morph Tpref was 2.3 ºC lower than average white and yellow morph Tpref. Our results add support to the idea thatP. erhardiicolor morphs have multivariate alternative phenotypes and present the possibility that thermally heterogeneous environments play a role in the maintenance of color polymorphism in this species.
Experience dependence of alpha rhythms and neural dynamics in mouse visual cortex
Authors: Riyahi Pouria , Phillips Marnie A. , Boley Nathaniel , Colonnese Matthew T. 
Published: November 2022

ABSTRACTThe role of experience in the development and maintenance of emergent network properties such as cortical oscillations and states is poorly understood. To define how early-life experience affects cortical dynamics in adult visual cortex, we examined the effects of two forms of blindness, bilateral loss of retinal input (enucleation) and degradation of visual input (eyelid-suture), on spontaneous activity in awake head-fixed mice of both sexes. Neither form of deprivation fundamentally altered the state-dependent regulation of firing-rates or local field potentials. However, each form of deprivation did cause a unique set of changes in network behavior. Laminar analysis revealed two different generative mechanisms for low-frequency synchronization, one prevalent during movement, the other during quiet-wakefulness. The former was absent in enucleated mice, suggesting a mouse homolog of human alpha oscillations. In addition, neurons in enucleated animals were less correlated and fired more regularly, but showed no change in mean firing-rate. Chronic lid-suture decreased firing rates during quiet-wakefulness, but not during movement, with no effect on neural correlations or regularity. Sutured animals showed a broadband increase in dEEG power and an increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary--rather than additive--effects of lid-suture and enucleation suggest that the development of these emergent network properties does not require vision but is plastic to modified input. Our results suggest a complex interaction of internal set-points and experience determines the expression of mature cortical activity, with low-frequency synchronization being particularly susceptible to early deprivation.SIGNIFICANCE STATEMENTThe developmental rules that guide how cortex balances internal homeostatic set points with external inputs to establish the emergent network level dynamics critical to its function are unclear. Using multiple methods of early deprivation, we show that the development of dynamics in mouse visual cortex is not dependent on the type of input. Rather, specific neural rhythms, firing-rate set points, and neural correlations are differentially modified by experience. Our deprivations identify one specific rhythm as a likely homolog to human alpha and suggest a mechanism for its loss in blindness. Our results advance our understanding of the regulatory mechanism leading to normal cortical processing, which is altered in blindness and multiple neural disorders.
Natural Killer activating multimeric immunotherapeutic complexes (NaMiX) induce cytotoxic activity and killing of HIV-1 infected cells
Authors: Schober Rafaela , Brandus Bianca , Laeremans Thessa , Iserentant Gilles , Dessilly Géraldine , Zimmer Jacques , Moutschen Michel , Aerts Joeri L , Dervillez Xavier , Seguin-Devaux Carole 
Published: November 2022

AbstractHIV-1 persists in viral reservoirs of latently infected CD4+T cells containing integrated replication-competent viral DNA. Combined Antiretroviral Therapy (cART) does not eradicate HIV-1 reservoirs and treatment interruption will ultimately lead to viral load rebound. HIV-1 infection dramatically reduces the proportion of functional NK cell subsets and increases the expression of the checkpoint inhibitors NKG2A and KIR2DL. In this regard, we developed novel recombinant molecules combining multimers of the IL-15/IL-15Rα complex with the single-chain fragment variables (scFvs) of NKG2A or KIR2DL, and named them as Natural killer activating Multimeric immunotherapeutic compleXes (NaMiX). NaMiX significantly improved the cytotoxic activity of NK cells against HIV-1 positive ACH-2 cells and resistant Raji cancer cells by increasing their degranulation capacity, release of granzyme B, perforin and IFN-γ expression. Targeting the NKG2A receptor had a stronger effect compared to the targeting of the KIR2DL receptor due to its higher expression on NK cells. In a viral inhibition assay using CD4+T cells from HIV-1 positive patients under cART, NaMiX initially increased viral replication which was subsequently inhibited by stimulated NK cells. In humanized NSG tg-huIL-15 mice showing functional NK cells, we observed enhanced activation, degranulation and killing by NK cells from the spleen of mice treated with anti-NKG2A NaMiX compared to the cells of control mice previously infected with HIV-1 and treated with cART. Although NaMiX did not delay viral load rebound after treatment interruption in a first attempt, it tend to decrease total HIV-1 DNA in the lungs of the mice. Blocking the inhibitory receptor NKG2A in combination with targeted multimers of IL-15 on NK cells could therefore be a promising immunotherapeutic strategy towards HIV-1 functional cure.
Immune response of primary and booster immunity of SARS-CoV-2 vaccination among patients with chronic liver disease
Authors: Song Ruixin , Yang Chao , Wang Jiayin , Li Qianqian , Chen Jing , Sun Kai , Lv Hongmin , Yang Yankai , Liang Jing , Ye Qing , Gao YanYing , Li Jun , Li Ying , Yan Junqing , Liu Ying , Wang Tao , Liu Changen , Wang Fei , Yin Weili , Xiang Huiling 
Published: November 2022

AbstractAimwe examined the humoral immune response and antibody dynamics after primary and booster vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients with chronic liver disease (CLD).MethodsWe enrolled patients with confirmed CLD and SARS-CoV-2 vaccination primary or booster immunity. Following primary or booster immunity, serological samples were gathered to detect novel coronavirus neutralizing antibodies (nCoV NTAb) and novel coronavirus spike receptor-binding proteins (nCoV S-RBD).ResultsThe positive rate of nCoV NTAb was 60.1% in Primary and 87.6% in Booster (P<0.001). The median level of nCoV NTAb was 11.6 AU/mL in Primary and 31.6 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 70.0% in Primary and 91.2% in Booster (P<0.001). The median level of nCoV S-RBD was 21.7 AU/mL in Primary and 110.6 AU/mL in Booster (P<0.001). Compared to the antibody level of primary immunity, 21 patients in whom SARS-CoV-2 vaccine antibodies were detected after both primary and booster immunizations showed an increase of 4.4 and 5.9 times in nCoV NTAb and nCoV S-RBD, respectively.ConclusionPatients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD.
Optimizing the Benefits of Mental Practice on Motor Acquisition and Consolidation with Moderate-Intensity Exercise
Authors: Monany Dylan Rannaud , Lebon Florent , Papaxanthis Charalambos 
Published: November 2022

AbstractThe optimization of mental practice (MP) protocols matters for sport and motor rehabilitation. In this study, we were interested in the benefits of moderate-intensity exercise in MP, given its positive effects on the acquisition and consolidation of motor skills induced by physical practice (PP). Four experimental groups were tested: i) physical practice without exercise (PP-Rest), ii) mental practice without exercise (MP-Rest), iii) mental practice preceded by Exercise (Exe-MP), and iv) mental practice followed by Exercise (MP-Exe). We hypothesized that exercise before MP would further increase speed and accuracy at a finger-sequence task measured right after MP (potentiation of motor acquisition), whereas exercise after MP would further increase speed and accuracy the day after MP (promotion of motor consolidation). Motor performance (movement speed and accuracy) was measured during a sequential finger tapping task before (Pre-Test), immediately after (Post-Test 0h, acquisition), and one day after practice (Post-Test 24h, consolidation). Results suggest that exercise before MP did not additionally improve motor acquisition in comparison to the MP-Rest group (both for accuracy and speed, p’s>0.05). Interestingly, moderate-intensity exercise after MP further increased performance during motor consolidation (speed, p=0.051; accuracy, p=0.028), at the level of the PP-Rest group. This novel finding represents a promising advance in the optimization of mental practice protocols in sport-related and rehabilitation settings.
A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types
Authors: Swygart David , Yu Wan-Qing , Takeuchi Shunsuke , Wong Rachel R. O.L. , Schwartz Gregory W. 
Published: November 2022

AbstractIn early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that divergence in the level of surround suppression occurs subcellularly, at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same set of bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.