bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond resource selection: emergent spatio-temporal distributions from animal movements and stigmergent interactions
Authors: Potts Jonathan R. , Giunta Valeria , Lewis Mark A. 
Published: March 2022

AbstractA principal concern of ecological research is to unveil the causes behind observed spatio-temporal distributions of species. A key tactic is to correlate observed locations with environmental features, in the form of resource selection functions or other correlative species distribution models. In reality, however, the distribution of any population both affects and is affected by those surrounding it, creating a complex network of feedbacks causing emergent spatio-temporal features that may not correlate with any particular aspect of the underlying environment. Here, we study the way in which the movements of populations in response to one another can affect the spatio-temporal distributions of ecosystems. We construct a stochastic individual-based modelling (IBM) framework, based on stigmergent interactions (i.e. organisms leave marks which cause others to alter their movements) between and within populations. We show how to gain insight into this IBM via mathematical analysis of a partial differential equation (PDE) system given by a continuum limit. We show how the combination of stochastic simulations of the IBM and mathematical analysis of PDEs can be used to categorise emergent patterns into homogeneous vs. heterogeneous, stationary vs. perpetually-fluctuating, and aggregation vs. segregation. In doing so, we develop techniques for understanding spatial bifurcations in stochastic IBMs, grounded in mathematical analysis. Finally, we demonstrate through a simple example how the interplay between environmental features and between-population stigmergent interactions can give rise to predicted spatial distributions that are quite different to those predicted purely by accounting for environmental covariates.
Thalamic control of sensory enhancement and sleep spindle properties in a biophysical model of thalamoreticular microcircuitry
Authors: Iavarone Elisabetta , Simko Jane , Shi Ying , Bertschy Marine , García-Amado María , Litvak Polina , Kaufmann Anna-Kristin , O’Reilly Christian , Amsalem Oren , Abdellah Marwan , Chevtchenko Grigori , Coste Benoît , Courcol Jean-Denis , Ecker András , Favreau Cyrille , Fleury Adrien Christian , Geit Werner Van , Gevaert Michael , Guerrero Nadir Román , Herttuainen Joni , Ivaska Genrich , Kerrien Samuel , King James G. , Kumbhar Pramod , Lurie Patrycja , Magkanaris Ioannis , Muddapu Vignayanandam Ravindernath , Nair Jayakrishnan , Pereira Fernando L. , Perin Rodrigo , Petitjean Fabien , Ranjan Rajnish , Reimann Michael , Soltuzu Liviu , Sy Mohameth François , Tuncel M. Anıl , Ulbrich Alexander , Wolf Matthias , Clascá Francisco , Markram Henry , Hill Sean L. 
Published: March 2022

AbstractThalamoreticular circuitry is known to play a key role in attention, cognition and the generation of sleep spindles, and is implicated in numerous brain disorders, but the cellular and synaptic mechanisms remain intractable. Therefore, we developed the first detailed computational model of mouse thalamus and thalamic reticular nucleus microcircuitry that captures morphological and biophysical properties of ∼14,000 neurons connected via ∼6M synapses, and recreates biological synaptic and gap junction connectivity. Simulations recapitulate multiple independent network-level experimental findings across different brain states, providing a novel unifying cellular and synaptic account of spontaneous and evoked activity in both wakefulness and sleep. Furthermore, we found that: 1.) inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness, in addition to its role in spindle generation; 2.) thalamic interactions generate the characteristic waxing and waning of spindle oscillations; and 3.) changes in thalamic excitability (e.g. due to neuromodulation) control spindle frequency and occurrence. The model is openly available and provides a new tool to interpret spindle oscillations and test hypotheses of thalamoreticular circuit function and dysfunction across different network states in health and disease.
A Single Multipurpose FSH–Blocking Therapeutic for Osteoporosis and Obesity
Authors: Gera Sakshi , Kuo Tan-Chun , Korkmaz Funda , Sant Damini , DeMambro Victoria , Gumerova Anisa , Sudha Kathayani , Padilla Ashley , Prevot Geoffrey , Munitz Jazz , Teunissen Abraham , van Leent Mandy , Post Tomas G.J.M. , Fernandes Jessica C. , Netto Jessica , Sultana Farhath , Shelly Eleanor , Kumar Pushkar , Cullen Liam , Chatterjee Jiya , Miyashita Sari , Kannangara Hasni , Bhongade Megha , Ievleva Kseniia , Muradova Valeriia , Batista Rogerio , Robinson Cemre , Macdonald Anne , Babunovic Susan , Saxena Mansi , Meseck Marcia , Caminis John , Iqbal Jameel , New Maria I. , Ryu Vitaly , Kim Se-Min , Cao Jay J. , Zaidi Neeha , Fayad Zahi , Lizneva Daria , Rosen Clifford J. , Yuen Tony , Zaidi Mone 
Published: March 2022

ABSTRACTPharmacological and genetic studies over the past decade have established FSH as an actionable target for diseases affecting millions, notably osteoporosis, obesity and Alzheimer’s disease (AD). Blocking FSH action prevents bone loss, fat gain and AD–like features in mice. We recently developed a first–in–class, humanized, epitope–specific FSH blocking antibody, MS-Hu6, with a KDof 7.52 nM. Using a GLP–compliant platform, we now report the efficacy of MS-Hu6 in preventing obesity and osteoporosis in mice, and parameters of acute safety in monkeys. Biodistribution studies using89Zr–labelled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone, bone marrow and fat depots. MS-Hu6 displayed a β phase t½of 13 days (316 hours) in humanizedTg32mice, and bound endogenous FSH. We tested 215 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze–thaw and at different temperatures, with minimal aggregation, and without self–, cross–, or hydrophobic interactions or appreciable binding to relevant human antigens. MS-Hu6 showed the same level of “humanness” as human IgG1in silico, and was non–immunogenic in ELISPOT assays for IL-2 and IFNγ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable and manufacturable, and is therefore poised for future human testing as a multipurpose therapeutic.
Keratinocyte-tethering modification for biologics enables location-precise treatment in mouse vitiligo
Authors: Hsueh Ying-Chao , Wang Yuzhen , Riding Rebecca L. , Catalano Donna E. , Lu Yu-Jung , Richmond Jillian M. , Siegel Don L. , Rusckowski Mary , Stanley John R. , Harris John E. 
Published: March 2022

ABSTRACTDespite the central role of IFNγ in vitiligo pathogenesis, systemic IFNγ neutralization is an impractical treatment option due to strong immunosuppression. However, most vitiligo patients present with less than 20% affected body surface area, which provides an opportunity for localized treatments that avoid systemic side effects. After identifying keratinocytes as key cells that amplify IFNγ signaling during vitiligo, we hypothesized that tethering an IFNγ neutralizing antibody to keratinocytes would limit anti-IFNγ effects to the treated skin for the localized treatment. To that end, we developed a bispecific antibody (BsAb) capable of blocking IFNγ signaling while binding to desmoglein expressed by keratinocytes. We characterized the effect of the BsAb in vitro, ex vivo, and in a mouse model of vitiligo. SPECT/CT biodistribution and serum assays after local footpad injection revealed that the BsAb had improved skin retention, faster elimination from the blood, and less systemic IFNγ inhibition than the non-tethered version. Furthermore, the BsAb conferred localized protection almost exclusively to the treated footpad during vitiligo that was not possible by local injection of the non-tethered anti-IFNγ antibody. Thus, keratinocyte-tethering proved effective while significantly diminishing off-tissue effects of IFNγ blockade, offering a new treatment strategy for localized skin diseases, including vitiligo.
Genetic Variation and Disease Severity of Respiratory Syncytial Viruses
Authors: Anderson Christopher S. , Zhang Yun , Corbett Anthony , Chu Chinyi , Grier Alexander , Wang Lu , Qiu Xing , Mccall Mathew , Topham David J. , Walsh Edward E. , Mariani Thomas J. , Scheuermann Richard , Caserta Mary T. 
Published: March 2022

AbstractRespiratory Syncytial Virus (RSV) disease in newborns ranges from mild symptoms to severe disease requiring hospitalization. RSV is classified into two subtypes (RSVA and RSVB) based on antigenic and genetic differences. The role these genomic variations play in disease severity remains unknown. Genome sequences were obtained using next-generation RNA sequencing on archived frozen nasal swabs of young children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998. Samples were chosen from both children hospitalized with severe RSV disease (inpatient) and those presenting with mild symptoms (outpatient) during their first cold-season. Both A and B subtypes demonstrated significant differences in the phylogeny and primary-protein structure during this time period. We found a significant association between RSV phylogeny over this time period and disease severity. For both subtypes, the G-protein demonstrated the greatest amino acid substitutions, although the number of amino acid substitutions was higher in the RSVA subtype. We found a significant association between G-protein variation and disease severity for RSVA, but not RSVB. For both subtypes, variation in the M2-2 protein was significantly associated with disease severity. These results suggest that the genetic variability of RSV proteins may contribute to disease severity in humans.ImportanceEach cold-season Respiratory Syncytial Virus (RSV) infects thousands of children in the US. Some will display mild cold symptoms while others develop severe disease, sometimes resulting in lifelong lung problems or fatality. RSV initiates infection and replicates in the nasopharynx. Substitutions in the RSV genome can be found in clinically isolated nasal-swab samples of RSV infected children. Whether these genome variations contribute to severe disease is unknown. Here we found a statistically significant association between RSV phylogeny and disease severity. Furthermore, we found specific RSV proteins (G and M2-2) whose amino acid variation was statistically associated with severe disease, although which protein was associated depended on subtype. Taken together, our results suggest that RSV genotype contributed to disease severity over this time period.
Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine
Authors: Kanokudom Sitthichai , Assawakosri Suvichada , Suntronwong Nungruthai , Chansaenroj Jira , Auphimai Chompoonut , Nilyanimit Pornjarim , Vichaiwattana Preeyaporn , Thongmee Thanunrat , Yorsaeng Ritthideach , Duangchinda Thaneeya , Chantima Warangkana , Pakchotanon Pattarakul , Srimuan Donchida , Thatsanatorn Thaksaporn , Klinfueng Sirapa , Mongkolsapaya Juthathip , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Honsawek Sittisak , Poovorawan Yong 
Published: March 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 μg-than the 30 μg-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 μg-than the 50 μg-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply.HighlightsThe 15 μg- and 30 μg-BNT162b2, and 50 μg- and 100 μg-mRNA-1273 booster doses were comparedBooster vaccination with the mRNA vaccine elicits high Ig and IgG anti-RBD in CoronaVac-vaccinated adultsNo differences were observed in antibody responses after the reduced or standard booster dose of the mRNA vaccine in CoronaVac-vaccinated adultsNeutralizing antibodies against the delta and omicron variants were significantly higher after the booster doseNeutralizing antibody titers were lower against the omicron variant than the delta variant in all vaccinated adults
Direct fluorescent labeling of NF186 and NaV1.6 in living primary neurons using bioorthogonal click chemistry
Authors: Stajković Nevena , Liu Yuanyuan , Arsić Aleksandra , Meng Ning , Lyu Hang , Zhang Nan , Grimm Dirk , Lerche Holger , Nikić-Spiegel Ivana 
Published: March 2022

AbstractThe axon initial segment (AIS) is a highly specialized neuronal compartment that regulates the generation of action potentials and maintenance of neuronal polarity. Despite its importance, live imaging of the AIS is challenging due to the limited number of suitable labeling methods. To overcome this limitation, we established a novel approach for live labeling of the AIS using unnatural amino acids (UAAs) and bioorthogonal click chemistry. The small size of the UAAs and the possibility of introducing them virtually anywhere into the target proteins make this method particularly suitable for live labeling and imaging of complex and spatially restricted proteins. With this approach, we labeled two large AIS components, the 186 kDa isoform of neurofascin (NF186) and the 260 kDa voltage-gated sodium channel (NaV1.6), and performed widefield and confocal microscopy in fixed and living neurons. Moreover, we demonstrated the applicability of this method by studying the localization of two epilepsy-causing NaV1.6 variants with a loss-of-function effect. Finally, to further improve the efficiency of the UAA incorporation, we developed adeno-associated viral (AAV) vectors for click labeling in primary neurons. The use of AAV vectors will facilitate the transfer of UAA-based click labeling technology to more complex biological systems, such as organotypic slice cultures, organoids, and animal models.
Intelligence and Visual Mismatch Negativity: Is Pre-Attentive Visual Discrimination Related to General Cognitive Ability?
Authors: Hilger Kirsten , Euler Matthew J. 
Published: March 2022

ABSTRACTElectroencephalography (EEG) has been used for decades to identify neurocognitive processes related to intelligence. Evidence is accumulating for associations with neural markers of higher-order cognitive processes (e.g., working memory); however, whether associations are specific to complex processes or also relate to earlier processing stages remains unclear. Addressing these issues has implications for improving our understanding of intelligence and its neural correlates. The mismatch negativity (MMN) is an event-related brain potential (ERP) that is elicited when, within a series of frequent standard stimuli, rare deviant stimuli are presented. As stimuli are typically presented outside the focus of attention, the MMN is suggested to capture automatic pre-attentive discrimination processes. However, the MMN and its relation to intelligence has largely only been studied in the auditory domain, thus preventing conclusions about the involvement of automatic discrimination processes in humans’ dominant sensory modality vision. Electroencephalography was recorded from 50 healthy participants during a passive visual oddball task that presented simple sequence violations as well as deviations within a more complex hidden pattern. Signed area amplitudes and fractional area latencies of the visual mismatch negativity (vMMN) were calculated with and without Laplacian transformation. Correlations between vMMN and intelligence (Raven’s Advanced Progressive Matrices) were of negligible to small effect sizes, differed critically between measurement approaches, and Bayes Factors provided anecdotal to substantial evidence for the absence of an association. We discuss differences between the auditory and visual MMN, the implications of different measurement approaches, and offer recommendations for further research in this evolving field.HIGHLIGHTS-Testing whether intelligence is related to automatic visual discrimination-Visual mismatch negativity (vMMN) as a neural indicator of pre-attentive processing-No association between intelligence and vMMN amplitudes or latencies-Critical differences between auditory and visual MMN?-Results partly depend on different measurement approaches
Insights of the role of estrogen in obesity from two models of ERα deletion
Authors: Saavedra-Peña Rocío del M. , Taylor Natalia , Rodeheffer Matthew S. 
Published: March 2022

AbstractSex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth are not understood. Here, we show that deletion of estrogen receptor alpha (ERα) from adipocytes using Adiponectin-cre does not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via PdgfRα-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with subcutaneous adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the PdgfRα-cre strain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon PdgfRα-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms, but are rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.
“Measurements of damage and repair in aging mice and humans reveals that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions”
Authors: Farrell S , Kane AE , Bisset E , Howlett SE , Rutenberg AD 
Published: March 2022

AbstractAs an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair rates from repeated observations of health deficits in mice and humans to explore the contribution of robustness and resilience, which respectively decrease damage rates and increase repair rates, to aging health. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening health in aging. A decline in robustness, however, has a greater effect than a decline in resilience on accelerating damage accumulation with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales towards organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice, and household wealth for humans. We find that these interventions affect both damage and repair rates – but in different proportions for different interventions. These findings have implications for how health in aging, and interventions targeting health, are conceptualized and assessed.
Earliest evidence for frugivory and seed dispersal by birds
Authors: Hu Han , Wang Yan , McDonald Paul G. , Wroe Stephen , O’Connor Jingmai K. , Bjarnason Alexander , Bevitt Joseph J. , Yin Xuwei , Zheng Xiaoting , Zhou Zhonghe , Benson Roger B.J. 
Published: March 2022

AbstractThe Early Cretaceous diversification of birds was a major event in the history of terrestrial ecosystems, occurring during the earliest phase of the Cretaceous Terrestrial Revolution. Frugivorous birds play an important role in seed dispersal today, and may have done so since their origins. However, evidence of this has been lacking. Jeholornis is one of the earliest-diverging birds, only slightly more derived than Archaeopteryx, but its cranial anatomy has been poorly understood, obscuring diet-related functional interpretations. Originally hypothesised to be granivorous based on seeds preserved as gut contents, this interpretation has become controversial. We conducted high-resolution synchrotron tomography on an exquisitely preserved new skull of Jeholornis, revealing remarkable cranial plesiomorphies combined with a specialised rostrum. We use this to provide a near-complete cranial reconstruction of Jeholornis, and exclude the possibility that Jeholornis was granivorous, based on morphometric analyses of the mandible (3D) and cranium (2D), and comparisons with the 3D alimentary contents of extant birds. We show that Jeholornis was at least seasonally frugivorous, providing the earliest evidence for fruit consumption in birds, and indicating that seed dispersal was present from early in the avian radiation. As highly-mobile seed dispersers, early frugivorous birds could expand the scope for biotic dispersal in plants, and may explain, in part, the subsequent evolutionary expansion of fruits, indicating a potential role of bird-plant interactions in the Cretaceous Terrestrial Revolution.
Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination
Authors: Paschold Lisa , Klee Bianca , Gottschick Cornelia , Willscher Edith , Diexer Sophie , Schultheiß Christoph , Simnica Donjete , Sedding Daniel , Girndt Matthias , Gekle Michael , Mikolajczyk Rafael , Binder Mascha 
Published: March 2022

AbstractHigh antibody affinity against the ancestral SARS-CoV-2 strain seems to be necessary (but not always sufficient) for the control of emerging immune-escape variants. Therefore, aiming at strong B cell somatic hypermutation - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the booster, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.Brief summaryPriming SARS-CoV-2 vaccinations generate antibodies from low-level matured B cells while the third vaccination strongly boosts somatic hypermutation potentially explaining different protection from immune-escape variants.