bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural correlates of individual facial recognition in a social wasp
Authors: Jernigan Christopher M. , Freiwald Winrich A. , Sheehan Michael J.
Published: April 2024

Individual recognition is critical for social behavior across species. Whether recognition is mediated by circuits specialized for social information processing has been a matter of debate. Here we examine the neurobiological underpinning of individual visual facial recognition inPolistes fuscatuspaper wasps. Front-facing images of conspecific wasps broadly increase activity across many brain regions relative to other stimuli. Notably, we identify a localized subpopulation of neurons in the protocerebrum which show specialized selectivity for front-facing wasp images, which we termwasp cells. Thesewasp cellsencode information regarding the facial patterns, with ensemble activity correlating with facial identity.Wasp cellsare strikingly analogous to face cells in primates, indicating that specialized circuits are likely an adaptive feature of neural architecture to support visual recognition.

One-Sentence Summary

We identify a localized population of neurons specifically tuned to wasp faces in a social wasp that has independently evolved individual facial recognition analogous to the face cells of primates.
Effects of antiretroviral treatment on central and peripheral immune response in mice with EcoHIV infection
Authors: Xie Qiaowei , Namba Mark D , Buck Lauren A , Park Kyewon , Jackson Joshua G , Barker Jacqueline M
Published: April 2024

HIV infection is an ongoing global health issue despite increased access to antiretroviral therapy (ART). People living with HIV (PLWH) who are virally suppressed through ART still experience negative health outcomes, including neurocognitive impairment. It is increasingly evident that ART may act independently or in combination with HIV infection to alter immune state, though this is difficult to disentangle in the clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays to assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of immune targets in the presence and absence of ART treatment in the EcoHIV mouse model. The findings identify effects of EcoHIV infection and of treatment with bictegravir (B), emtricitabine (F) and tenofovir alafenamide (TAF) on expression of numerous immune targets. In the NAc, this included EcoHIV-induced increases in IL-1α and IL-13 expression and B/F/TAF-induced reductions in KC/CXCL1. In the periphery, EcoHIV suppressed IL-6 and LIF expression, while B/F/TAF reduced IL-12p40 expression. In absence of ART, IBA-1 expression was negatively correlated with CX3CL1 expression in the NAc of EcoHIV-infected mice. These findings identify distinct effects of ART and EcoHIV infection on peripheral and central immune factors and emphasize the need to consider ART effects on neural and immune outcomes.
Feedback scales the spatial tuning of cortical responses during both visual working memory and long-term memory
Authors: Woodry Robert , Curtis Clayton E , Winawer Jonathan
Published: April 2024

Perception, working memory, and long-term memory each evoke neural responses in visual cortex. While previous neuroimaging research on the role of visual cortex in memory has largely emphasized similarities between perception and memory, we hypothesized that responses in visual cortex would differ depending on the origins of the inputs. Using fMRI, we quantified spatial tuning in visual cortex while participants (both sexes) viewed, maintained in working memory, or retrieved from long-term memory a peripheral target. In each condition, BOLD responses were spatially tuned and aligned with the targets polar angle in all measured visual field maps including V1. As expected given the increasing sizes of receptive fields, polar angle tuning during perception increased in width up the visual hierarchy from V1 to V2, V3, hV4, and beyond. In stark contrast, the tuned responses were broad across the visual hierarchy during long-term memory (replicating a prior result) and during working memory. This pattern is consistent with the idea that mnemonic responses in V1 stem from top-down sources, even when the stimulus was recently viewed and is held in working memory. Moreover, in long-term memory, trial-to-trial biases in these tuned responses (clockwise or counterclockwise of target), predicted matched biases in memory, suggesting that the reinstated cortical responses influence memory guided behavior. We conclude that feedback widens spatial tuning in visual cortex during memory, where earlier visual maps inherit broader tuning from later maps thereby impacting the precision of memory.
In search of a conditioned place preference test to assess the severity of experimental procedures
Authors: Jaap Anne , Kahnau Pia , Lewejohann Lars
Published: April 2024

To compare the severity of experimental procedures and behavioural tests from an animal’s perspective novel methods are needed. In theory, one feasible approach could be the use of a conditioned place preference test (CPP). In this test the preference for a certain area in a test apparatus is associated with an experimental treatment.

Traditionally, the CPP is used to investigate, for example, the effects of drugs. Here, we wanted to develop a protocol, which instead would enable us to compare the effects of different experimental procedures conducted with mice.

Nine experiments with C57BL/6J mice were performed, varying the setup, the procedure duration, the neutral to be conditioned stimuli (NS→CS; visual and/or textual), and the unconditioned stimuli (US; fixation, food reward, or weighing) as well as the presentation order (NS before, after, or parallel to US).

Unfortunately, none of the tested protocol resulted in a distinct preference. Moreover, even simple protocols using food reward as a treatment failed to result in a conditioned place preference. Overall, none of the protocols was sufficient to form a reliable association between NS and US. We have scrutinized the experimental setup in detail, and we cannot present a solution yet. However, hopefully, our findings will help to create a working CPP to compare the severity of different experimental procedures for mice.
A registration strategy to characterize DTI-observed changes in skeletal muscle architecture due to passive shortening
Authors: Hooijmans Melissa T. , Lockard Carly A. , Zhou Xingyu , Coolbaugh Crystal , Guzman Roberto Pineda , Kersh Mariana E. , Damon Bruce M.
Published: April 2024

Skeletal muscle architecture is a key determinant of muscle function. Architectural properties such as fascicle length, pennation angle, and curvature can be characterized using Diffusion Tensor Imaging (DTI), but acquiring these data during a contraction is not currently feasible. However, an image registration-based strategy may be able to convert muscle architectural properties observed at rest to their contracted state. As an initial step toward this long-term objective, the aim of this study was to determine if an image registration strategy could be used to convert the whole-muscle average architectural properties observed in the extended joint position to those of a flexed position, following passive rotation. DTI and high-resolution fat/water scans were acquired in the lower leg of seven healthy participants on a 3T MR system in +20° (plantarflexion) and −10° (dorsiflexion) foot positions. The diffusion and anatomical images from the two positions were used to propagate DTI fiber-tracts from seed points along a mesh representation of the aponeurosis of fiber insertion. The −10° and +20° anatomical images were registered and the displacement fields were used to transform the mesh and fiber-tracts from the +20° to the −10° position. Student’s pairedt-tests were used to compare the mean architectural parameters between the original and transformed fiber-tracts. The whole-muscle average fiber-tract length, pennation angle, curvature, and physiological cross-sectional areas estimates did not differ significantly. DTI fiber-tracts in plantarflexion can be transformed to dorsiflexion position without significantly affecting the average architectural characteristics of the fiber-tracts. In the future, a similar approach could be used to evaluate muscle architecture in a contracted state.
Distinct mechanisms of visual and sound adaptation in the cat visual cortex
Authors: Belkacemi Yassine Yahia , Hospital Solène , Chanauria Nayan , Flouty Oliver , Molotchnikoff Stéphane , Bharmauria Vishal
Published: April 2024

Sensory areas exhibit modular selectivity to stimuli, but they can also respond to features outside of their basic modality. Several studies have shown cross-modal plastic modifications between visual and auditory cortices; however, the exact mechanisms of these modifications are yet not completely known. To this aim, we investigated the effect of 12 minutes of visualvs.sound adaptation [forceful application of a non-optimal stimulus to a neuron(s) under observation] on the infra- and supra-granular primary visual neurons (V1) of the cat (Felis catus). Previous reports showed that both protocols induced orientation tuning shifts, but sound increased the bandwidths. Here, we compared visualvs.sound adaptation effects, specifically analysing the raw tuning curves by computing the area under the curve (AUC) on a trial-by-trial basis. We report that sound adaptation elicited broader tuning curves accompanied with increased variance in the supra- and infra-granular layers, compared with visual adaptation. These findings suggest unique modulation of dendritic structure by distinct adaptation protocols, resulting in disparate tunings. We suggest that broader tuning curves after sound adaptation may keep the visual cortex prepared across a spectrum of abstract representations that match with visual stimuli.
Neuropathic pain in a chronic CNS injury model is mediated by CST-targeted spinal interneurons
Authors: Guan Xiaofei , Zhu Yanjie , Zhong Jian , Hollis Edmund
Published: April 2024

Chronic neuropathic pain is a persistent and debilitating outcome of traumatic central nervous system injury, affecting up to 80% of individuals with chronic injury. Post-injury pain is refractory to clinical treatments due to the limited understanding of the brain-spinal cord circuits that underlie pain signal processing. The corticospinal tract (CST) plays critical roles in sensory modulation during skilled movements and tactile sensation; however, a direct role for the CST in injury-associated neuropathic pain is unclear. Here we show that complete, selective CST transection at the medullary pyramids leads to hyperexcitability within lumbar deep dorsal horn and hindlimb allodynia in chronically injured adult mice. Chemogenetic regulation of CST-targeted lumbar spinal interneurons demonstrates that dysregulation of activity in this circuit underlies the development of tactile allodynia in chronic injury. Our findings shed light on an unrecognized circuit mechanism implicated in CNS injury-induced neuropathic pain and provide a novel target for therapeutic intervention.
A protective role for B-1 cells and oxidation-specific epitope IgM in lung fibrosis
Authors: Sturek Jeffrey M. , Hannan Riley T. , Upadhye Aditi , Otoupalova Eva , Faron Edwin T. , Atya Amr A.E. , Thomas Cassidy , Johnson Vernerdean , Miller Andrew , Garmey James C. , Burdick Marie D. , Barker Thomas H. , Kadl Alexandra , Shim Yun M. , McNamara Coleen A.
Published: April 2024

Idiopathic pulmonary fibrosis (IPF) is a morbid fibrotic lung disease with limited treatment options. The pathophysiology of IPF remains poorly understood, and elucidation of the cellular and molecular mechanisms of IPF pathogenesis is key to the development of new therapeutics. B-1 cells are an innate B cell population which play an important role linking innate and adaptive immunity. B-1 cells spontaneously secrete natural IgM and prevent inflammation in several disease states. One class of these IgM recognize oxidation-specific epitopes (OSE), which have been shown to be generated in lung injury and to promote fibrosis. A main B-1 cell reservoir is the pleural space, adjacent to the typical distribution of fibrosis in IPF. In this study, we demonstrate that B-1 cells are recruited to the lung during injury where they secrete IgM to OSE (IgMOSE). We also show that the pleural B-1 cell reservoir responds to lung injury through regulation of the chemokine receptor CXCR4. Mechanistically we show that the transcription factorId3is a novel negative regulator of CXCR4 expression. Using mice with B-cell specific Id3 deficiency, a model of increased B-1b cells, we demonstrate decreased bleomycin-induced fibrosis compared to littermate controls. Furthermore, we show that mice deficient in secretory IgM (sIgM-/-) have higher mortality in response to bleomycin-induced lung injury, which is partially mitigated through airway delivery of the IgMOSEE06. Additionally, we provide insight into potential mechanisms of IgM in attenuation of fibrosis through RNA sequencing and pathway analysis, highlighting complement activation and extracellular matrix deposition as key differentially regulated pathways.
Improved prediction of stabilizing mutations in proteins by incorporation of mutational effects on ligand binding
Authors: Ganesan Srivarshini , Mittal Nidhi , Bhat Akash , Adiga Rachna S. , Ganesan Ananthakrishnan , Nagarajan Deepesh , Varadarajan Raghavan
Published: April 2024

While many computational methods accurately predict destabilizing mutations, identifying stabilizing mutations has remained a challenge, due to their relative rarity. We tested ΔΔG0predictions from computational predictors such as Rosetta, ThermoMPNN, RaSP, and DeepDDG, using eighty-two mutants of the bacterial toxin CcdB as a test case. On this dataset, the best computational predictor is ThermoMPNN which identifies stabilizing mutations with a precision of 68%. However, the average increase in Tmfor these predicted mutations was only 1°C for CcdB, and predictions were poorer for a more challenging target, influenza neuraminidase. Using data from multiple previously described yeast surface display libraries andin vitrothermal stability measurements, we trained logistic regression models to identify stabilizing mutations with a precision of 90% and an average increase in Tmof 3°C for CcdB. When such libraries contain a population of mutants with significantly enhanced binding relative to the corresponding wild type, there is no benefit in using computational predictors. It is then possible to predict stabilizing mutations without any training, simply by examining the distribution of mutational binding scores. This avoids laborious steps ofin vitroexpression, purification, and stability characterization. When this is not the case, combining data from computational predictors with high-throughput experimental binding data enhances the prediction of stabilizing mutations. However, this requires training on stability data measuredin vitrowith known stabilized mutants. It is thus feasible to predict stabilizing mutations rapidly and accurately for any system of interest that can be subjected to a binding selection or screen.
Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo
Authors: Vakaniaki Emmanuel H. , Kacita Cris , Kinganda-Lusamaki Eddy , O’Toole Áine , Wawina-Bokalanga Tony , Mukadi-Bamuleka Daniel , Aziza Adrienne Amuri , Malyamungu-Bubala Nadine , Kumbana Franklin Mweshi , Mutimbwa-Mambo Léandre , Belesi-Siangoli Freddy , Mujula Yves , Parker Edyth , Muswamba-Kayembe Pauline-Chloé , Nundu Sabin S. , Lushima Robert S. , Cigolo Jean Claude Makangara , Mulopo-Mukanya Noella , Simbu Elisabeth Pukuta , Akil-Bandali Prince , Kavunga Hugo , Vercauteren Koen , Sam-Agudu Nadia A. , Mills Edward J , Tshiani-Mbaya Olivier , Hoff Nicole A. , Rimoin Anne W. , Hensley Lisa E. , Kindrachuk Jason , Ayouba Ahidjo , Peeters Martine , Delaporte Eric , Ahuka-Mundeke Steve , Nachega Jean B. , Muyembe-Tamfum Jean-Jacques , Rambaut Andrew , Liesenborghs Laurens , Mbala-Kingebeni Placide ,   the Mpox Research Consortium
Published: April 2024

Background

Monkeypox virus (MPXV) attracted global attention in 2022 during a widespread outbreak linked primarily to sexual contact. Clade I MPXV is prevalent in Central Africa and characterized by severe disease and high mortality, while Clade II is confined to West Africa and associated with milder illness. A Clade IIb MPXV emerged in Nigeria in 2017, with protracted human-to-human transmission a forerunner of the global Clade II B.1 lineage outbreak in 2022. In October 2023, a large mpox outbreak emerged in the Kamituga mining region of the Democratic Republic of the Congo (DRC), of which we conducted an outbreak investigation.

Methods

Surveillance data and hospital records were collected between October 2023 and January 2024. Blood samples and skin/oropharyngeal swabs were obtained for molecular diagnosis at the National Institute of Biomedical Research, Kinshasa. MPXV genomes were sequenced and analyzed using Illumina NextSeq 2000 and bioinformatic tools.

Results

The Kamituga mpox outbreak spread rapidly, with 241 suspected cases reported within 5 months of the first reported case. Of 108 confirmed cases, 29% were sex workers, highlighting sexual contact as a key mode of infection. Genomic analysis revealed a distinct MPXV Clade Ib lineage, divergent from previously sequenced Clade I strains in DRC. Predominance of APOBEC3-type mutations and estimated time of emergence around mid-September 2023 suggest recent human-to-human transmission.

Conclusions

Urgent measures, including reinforced, expanded surveillance, contact tracing, case management support, and targeted vaccination are needed to contain this new pandemic-potential Clade Ib outbreak.
Prevalence and impact of foot peripheral neuropathy in Sytemic Sclerosis (SSc): results from a single centre cross-sectional study
Authors: Alcacer-Pitarch Begonya , Di Battista Marco , Redmond Anthony C. , Keenan Anne-Maree , Di Donato Stefano , Buch Maya H. , Del Galdo Francesco
Published: April 2024

Introduction

Peripheral Sensory Neuropathy (PSN) is an under-recognized feature in systemic sclerosis (SSc). Moreover, SSc foot involvement is frequent but poorly investigated. We aimed to provide a detailed characterization of foot peripheral neuropathy in a large cohort of SSc patients, describing its associations with disease-specific features, physical disability and Quality of Life (QoL).

Methods

SSc patients and healthy controls (HC) comparable for age and gender, were enrolled in a cross-sectional observational case-control study. All subjects underwent a detailed quantitative sensory testing (QST) of feet evaluating touch, vibratory, thermal, and pain sensitivity; ultimately investigating the presence of large and small fiber neuropathy. Neuroptahtic symptoms were captured through a numerical rating scale assessing the presence of paraesthesia, numbness, burning, and stabbing pain. While the Manchester Foot Pain and Disability Index (MFPDI), SSc Health Assessment Questionnaire Disability Index (HAQ-DI), and the Systemic Sclerosis Quality of Life (SScQoL) needs-based questionnaire were used to capture the impact of the PSN on foot disability and QoL.

Results

109 SSc patients (88.1% female, median age 59.0 years) and 51 HC were enrolled. SSc patients presented with a significant median reduction of areas with preserved tactile sensitivity (14 IQR 4; p<0.001), and a delayed vibration perception threshold (1.7 µm IQR 3.0; p=0.01). Regarding thermoreceptor impairment, they presented with signifiantlly higer cold and warm thresholds (27.0 °C, IQR 3.0; vs 28.2 °C, p<0.001; 38.4 °C IQR 4.6, p=0.003 respectivelly), greater warm-cold threshold range (11.2 °C, IQR 6.9, p<0.001), and higher heat-induced pain threshold (44.8 °C, IQR 3.5; p<0.001),. At group level, 85.3% patients showed PSN on the feet, with 80% having small fibre involvement and 57% having large fiber neuropathy; while the coexistence of the two was present in 51.4% of the cases. Leaving only 14% without neuropathy. From those patients with PSN, 80.6% reported at least one neuropathic symptom, while 18% were asymptomatic. PSN was associated with age, smoking, foot ulceration,disease duration and corticosteroids use. Patients with neuropathic symptoms reported worse physical function, worse foot disability, and poorer QoL.

Conclusion

Foot PSN presents as common and disabling manifestation in patients with SSc, involving both large and small fibers, often co-existing. Clinically, the presence of neuropathic symptoms might serve as an indicator of PSN, although it can have a subclinical presentation. Hence, PSN assessment should be included as part of the workup of the SSc patient .
Evaluation of Artificial Intelligence (AI)-basedin silicotools for variant classification in clinically actionable NSCLC variants
Authors: Kim Eugene , Duarte Samantha E , Yu Emma , Hong Ilene , Lee Grace , Chae Young Kwang
Published: April 2024

Introduction/Background

Genetic variants beyond FDA-approved drug targets are often identified in non-small cell lung cancer (NSCLC) patients. Although the performances ofin silicotools in predicting variant pathogenicity have been analyzed in previous studies, they have not been analyzed for actionable targets of FDA-approved therapies for NSCLC. The aim of this study is to compare the performance of commonly usedin silicotools in classifying the pathogenicity of actionable variants in NSCLC.

Materials and Methods

We evaluated the performance of the followingin silicotools: Polyphen-2 (HumDiv, HumVar), Align-GVGD, MutationTaster2021, CADD, CONDEL, and REVEL. A curated set of targetable NSCLC missense variants (n=236) was used. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Matthews correlation coefficient (MCC) of eachin silicotool was determined.

Results

The most recently released MutationTaster2021 demonstrated the highest performance in terms of accuracy, specificity, PPV, and MCC, but was outperformed by CADD for both sensitivity and NPV. Although some tools demonstrated high sensitivities, all tools except MutationTaster2021 displayed markedly low overall specificities, as low as 23%.

Conclusion

The collective results indicate that the evaluatedin silicotools can provide guidance in predicting the pathogenicity of NSCLC missense variants, but are not fully reliable. The tools analyzed in this study could be acceptable to rule out pathogenicity in variants given their higher sensitivities, but are limited when it comes to identifying pathogenicity in variants due to low specificities.

Highlights

MutationTaster2021 demonstrated the highest overall performance

CADD demonstrated the highest sensitivity (99.19%) and NPV (96.55%).

All tools but MutationTaster2021 demonstrated low specificities, as low as 23%

An individual predictor outperformed 3 meta predictors

Performance variability suggests caution when usingin silicotools in the clinic
The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures
Authors: Yun S , Kiffer FC , Bancroft GL , Guzman CS , Soler I , Haas HA , Shi R , Patel R , Lara-Jiménez J , Kumar PL , Tran FH , Ahn KJ , Rong Y , Luitel K , Shay JW , Eisch AJ
Published: April 2024

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew’s longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.
SleepInvestigatoR: A flexible R function for analyzing scored sleep in rodents
Authors: Gamble Mackenzie C. , Williams Benjamin R. , McKenna James T. , Logan Ryan W.
Published: April 2024

Analyzing scored sleep is a fundamental prerequisite to understanding how sleep changes between health and disease. Classically, this is accomplished by manually calculating various measures (e.g., percent of non-rapid eye movement sleep) from a collection of scored sleep files. This process can be tedious and error prone especially when studies include a large number of animals or involve long recording sessions. To address this issue, we present SleepInvestigatoR, a versatile tool that can quickly organize and analyze multiple scored sleep files into a single output. The function is written in the open-source statistical language R and has a total of 25 parameters that can be set to match a wide variety of experimenter needs. SleepInvestigatoR delivers a total of 22 unique measures of sleep, including all measures commonly reported in the rodent literature. A simple plotting function is also provided to quickly graph and visualize the scored data. All code is designed to be implemented with little formal coding knowledge and step-by-step instructions are provided on the corresponding GitHub page. Overall, SleepInvestigatoR provides the sleep researcher a critical tool to increase efficiency, interpretation, and reproducibility in analyzing scored rodent sleep.
Does hybridisation with an invasive species threaten Europe’s most endangered reptile? Genomic assessment of Aeolian lizards on Vulcano island
Authors: Paris Josephine R , Ficetola Gentile Francesco , Obiol Joan Ferrer , Rocha Iolanda Silva- , Carretero Miguel Angel , Salvi Daniele
Published: April 2024

Interspecific hybridisation can be consequential for rare and insular endemic species. The Critically Endangered Aeolian wall lizard,Podarcis raffonei, severely declined due to interactions with the invasive Italian wall lizard,Podarcis siculus. The largest population ofP. raffoneisurvives on a narrow peninsula (Capo Grosso) that is mildly connected to the island of Vulcano, which has been entirely invaded byP. siculus. Recent observation of individuals with an intermediate phenotype raised concern over the risk that hybridisation might swamp this last stronghold. We genetically characterised lizards from Vulcano using genome-wide SNPs, considering individuals showing multiple phenotypes (native, invasive, and “intermediate”). Hybridisation rate was low (∼3%), with just two F1 hybrids and two backcrosses. However, pureP. raffoneishowed extremely low genetic diversity, a very small effective population size, and a low NE/NCratio. Management strategies are urgently needed to control invasive species and maintain the genetic diversity ofP. raffonei.
Differences in factors determining taxon-based and trait-based community structures: a field test using zooplankton
Authors: Suzuki Hiromichi , Ichiyanagi Hidetaka , Kass Jamie M , Urabe Jotaro
Published: April 2024

Ecological community structure, which has traditionally been described in terms of taxonomic units, is driven by a combination of dispersal and environmental filters. Traits have recently been recognized as alternative units for quantifying community parameters, but they may have important differences with taxonomic units. For example, as taxon-based community structures are determined by the identities of individual species, they may be more limited by species' dispersal constraints, whereas trait-based community structures may be more regulated by environmental conditions because functional traits should have stronger linkages to habitat types rather than their specific locations. This suggests that the relative importance of dispersal and environmental filters may vary depending on the units employed to define community structure, yet how the contributions of these filters compare remains unclear. Zooplankton in lakes and reservoirs are an ideal system for examining the relative importance of these filters as they have moderate dispersal ability and inhabit communities in isolated habitats. In this study, we examined zooplankton assemblages in 87 artificial reservoirs throughout the Japanese archipelago to test the hypothesis that environmental filters play a more dominant role in determining trait-based community structures than taxon-based structures. To describe trait-based communities, we categorized zooplankton taxa into 12 functional groups using ecologically meaningful traits, including body size, feeding habits and mode, and population growth rate. We then examined the effects of both spatial configuration (reflecting dispersal filters) and environmental variables such as reservoir size and depth, trophic conditions, and fish assemblages for taxon- and trait-based community structures. Although variation in the taxon-based structure was explained equally well by spatial and environmental variables, variation in the trait-based structure explained by environmental variables was nearly twice that of spatial variables. These results support the idea that environmental filters play a more central role in determining trait-based community structures, and show that the relative importance of spatial and environmental filters changes with the way we define community structure.
Role and modulation of various spinal pathways for human upper limb control in different gravity conditions
Authors: Bruel Alice , Bacha Lina , Boehly Emma , De Trogoff Constance , Represa Luca , Courtine Gregoire , Ijspeert Auke
Published: April 2024

Humans can perform movements in various physical environments and positions (corresponding to different experienced gravity), requiring the interaction of the musculoskeletal system, the neural system and the external environment. The neural system is itself comprised of several interactive components, from the brain mainly conducting motor planning, to the spinal cord (SC) implementing its own motor control centres through sensory reflexes. Nevertheless, it remains unclear whether similar movements in various environmental dynamics necessitate replanning modulation at the brain level, correcting modulation at the spinal level, or both. Here, we addressed this question by focusing on upper limb motor control in various gravity conditions (magnitudes and directions) and using neuromusculoskeletal simulation tools. We integrated supraspinal sinusoidal commands with a modular SC model controlling a musculoskeletal model to reproduce recorded elbow flexion-extension trajectories (kinematics and EMGs) in different contexts. We first studied the role of various spinal pathways (such as stretch reflexes) in movement smoothness and robustness against perturbation. Then, we optimised the supraspinal sinusoidal commands without and with a fixed SC model including stretch reflexes to reproduce a target trajectory in various gravity conditions. Inversely, we fixed the supraspinal commands and optimised the spinal synaptic strengths in the different environments. In the first optimisation context, the presence of SC resulted in easier optimisation of the supraspinal commands (faster convergence, better performance). The main supraspinal commands modulation was found in the flexor sinusoid’s amplitude, resp. frequency, to adapt to different gravity magnitudes, resp. directions. In the second optimisation context, the modulation of the spinal synaptic strengths also remarkably reproduced the target trajectory for the mild gravity changes. We highlighted that both strategies of modulation of the supraspinal commands or spinal stretch pathways can be used to control movements in different gravity environments. Our results thus support that the SC can assist gravity compensation.
Poseidon – A framework for archaeogenetic human genotype data management
Authors: Schmid Clemens , Ghalichi Ayshin , Lamnidis Thiseas C. , Mudiyanselage Dhananjaya B. A. , Haak Wolfgang , Schiffels Stephan
Published: April 2024

1

The study of ancient human genomes, archaeo- or palaeogenetics, has accelerated in the last ten years, with now thousands of new ancient genomes being released each year. Operating at the interface of genetics, anthro-pology and archaeology, this data includes features from all three fields, including rich meta- and context-data, for example regarding spatiotemporal provenience. While archives and standards for genetic sequencing data al-ready exist, no such infrastructure exists for combined genetic and meta-data that could ensure FAIR principles across the field. Here, we present Poseidon, a framework for open and FAIR data handling in archaeogenetics, including a specified package format, software tools, and public, community-maintained online archives. Poseidon emphasises human- and machine-readable data storage, the development of convenient and interoperable command line software, and a high degree of source granularity to elevate the original data publication to the main unit of long-term curation.
What underlies exceptional memory function in older age? No evidence for aging-specific relationships to hippocampal atrophy and retrieval activity
Authors: Fjell Anders M. , Sneve Markus H. , Amlien Inge K , Grydeland Håkon , Mowinckel Athanasia M. , Vidal-Piñeiro Didac , Sørensen Øystein , Walhovd Kristine B.
Published: April 2024

Some older adults show superior memory performance compared to same-age peers, even performing on par with young participants. These are often referred to asSuperAgers. It is not known whether their superior memory function is caused by special features of their brains in aging, or whether superior memory has the same brain foundation throughout adult life. To address this, we measured hippocampal volume and atrophy, microstructural integrity by diffusion tensor imaging, and activity during an episodic memory encoding and retrieval task, in 277 cognitively healthy adults (age 20.1-81.5 years at baseline, mean 49.2 years). For quantification of hippocampal atrophy, all participants had repeated MRIs, from two to seven examinations, covering a mean of 9.3 years between first and last scan (2.5-17.3 years). 15.7% of the participants above 60 years had episodic memory scores above the mean of the young and middle-aged participants and were classified as SuperAgers. We found that superior memory in older adults was associated with higher retrieval activity in the anterior hippocampus and less hippocampal atrophy. However, there were no significant age-interactions, suggesting that the relationships reflected stable correlates of superior memory function. Although SuperAgers had superior memory compared to their same-age peers, they still performed worse than the best-performing young participants. Further, age-memory performance curves across the full age-range were similar for participants with superior memory performance compared to those with normal and low performance. These trajectories were based on cross-sectional data, but do not indicate preserved memory among the superior functioning older adults. In conclusion, the current results confirm that aspects of hippocampal structure and function are related to superior memory across age, without evidence to suggest that SuperAgers have special features compared to their younger counterparts.
A deep learning pipeline for time-lapse camera monitoring of insects and their floral environments
Authors: Bjerge Kim , Karstoft Henrik , Mann Hjalte M. R. , Høye Toke T.
Published: April 2024

Arthropods, including insects, represent the most diverse group and contribute significantly to animal biomass. Automatic monitoring of insects and other arthropods enables quick and efficient observation and management of ecologically and economically important targets such as pollinators, natural enemies, disease vectors, and agricultural pests. The integration of cameras and computer vision facilitates innovative monitoring approaches for agriculture, ecology, entomology, evolution, and biodiversity. However, studying insects and their interactions with flowers and vegetation in natural environments remains challenging, even with automated camera monitoring.

This paper presents a comprehensive methodology to monitor abundance and diversity of arthropods in the wild and to quantify floral cover as a key resource. We apply the methods across more than 10 million images recorded over two years using 48 insect camera traps placed in three main habitat types. The cameras monitor arthropods, including insect visits, on a specific mix ofSedumplant species with white, yellow and red/pink colored of flowers. The proposed deep-learning pipeline estimates flower cover and detects and classifies arthropod taxa from time-lapse recordings. However, the flower cover serves only as an estimate to correlate insect activity with the flowering plants. Color and semantic segmentation with DeepLabv3 are combined to estimate the percent cover of flowers of different colors. Arthropod detection incorporates motion-informed enhanced images and object detection with You-Only-Look-Once (YOLO), followed by filtering stationary objects to minimize double counting of non-moving animals and erroneous background detections. This filtering approach has been demonstrated to significantly decrease the incidence of false positives, since arthropods, occur in less than 3% of the captured images.

The final step involves grouping arthropods into 19 taxonomic classes. Seven state-of-the-art models were trained and validated, achievingF1-scores ranging from 0.81 to 0.89 in classification of arthropods. Among these, the final selected model, EfficientNetB4, achieved an 80% average precision on randomly selected samples when applied to the complete pipeline, which includes detection, filtering, and classification of arthropod images collected in 2021. As expected during the beginning and end of the season, reduced flower cover correlates with a noticeable drop in arthropod detections. The proposed method offers a cost-effective approach to monitoring diverse arthropod taxa and flower cover in natural environments using time-lapse camera recordings.
Snorkel-tag Based Affinity Chromatography for Recombinant Extracellular Vesicle Purification
Authors: Bobbili Madhusudhan Reddy , Görgen André , Yan Yan , Vogt Stefan , Gupta Dhanu , Corso Giulia , Barbaria Samir , Patrioli Carolina , Weilner Sylvia , Pultar Marianne , Jacak Jaroslaw , Hackl Matthias , Schosserer Markus , Grillari Regina , Kjems Jorgen , EL Andaloussi Samir , Grillari Johannes
Published: April 2024

Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine are still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue-specific EV cargo information. Here, we present CD81, an EV surface marker protein, genetically fused to series of tags with additional transmembrane domain to be displayed on the EV surface, which we term Snorkel-tag. This system enables to affinity purify EVs from complex matrices in a non-destructive form. In future applications, this strategy will allow generating transgenic animals to enable tracing and analyzing EVs, and their cargo in physiological and pathophysiological set-ups, and facilitate the development of EV based diagnostic tools in murine models which can be translated to humans.
Chromatin accessibility variation provides insights into missing regulation underlying immune-mediated diseases
Authors: Jeong Raehoon , Bulyk Martha L.
Published: April 2024

Most genetic loci associated with complex traits and diseases through genome-wide association studies (GWAS) are noncoding, suggesting that the causal variants likely have gene regulatory effects. However, only a small number of loci have been linked to expression quantitative trait loci (eQTLs) detected currently. To better understand the potential reasons for many trait-associated loci lacking eQTL colocalization, we investigated whether chromatin accessibility QTLs (caQTLs) in lymphoblastoid cell lines (LCLs) explain immune-mediated disease associations that eQTLs in LCLs did not. The power to detect caQTLs was greater than that of eQTLs and was less affected by the distance from the transcription start site of the associated gene. Meta-analyzing LCL eQTL data to increase the sample size to over a thousand led to additional loci with eQTL colocalization, demonstrating that insufficient statistical power is still likely to be a factor. Moreover, further eQTL colocalization loci were uncovered by surveying eQTLs of other immune cell types. Altogether, insufficient power and context-specificity of eQTLs both contribute to the ‘missing regulation.’
Influenza virus antibodies inhibit antigen-specificde novoB cell responses in mice
Authors: Goodwin Eileen , Gibbs James S. , Yewdell Jonathan W. , Eisenlohr Laurence C. , Hensley Scott E.
Published: April 2024

Antibody responses to influenza vaccines tend to be focused on epitopes encountered during prior influenza exposures, with little production ofde novoresponses to novel epitopes. To examine the contribution of circulating antibody to this phenomenon, we passively transferred a hemagglutinin (HA)-specific monoclonal antibody (mAb) into mice before immunizing with whole inactivated virions. The HA mAb inhibitedde novoHA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to a second antigen in the vaccine, neuraminidase (NA), were uninhibited. The HA mAb potently inhibitedde novoantibody responses against epitopes near the HA mAb binding site. The HA mAb also promoted IgG1 class switching, an effect that, unlike the inhibition of HA responses, relied on signaling through Fc-gamma receptors. These studies suggest that circulating antibodies inhibitde novoB cell responses in an antigen-specific manner, which likely contributes to differences in antibody specificities elicited during primary and secondary influenza virus exposures.
Association of 10 VEGF Family Genes with Alzheimer’s Disease Endophenotypes at Single Cell Resolution
Authors: Wu Yiyang , Libby Julia B , Dumitrescu Logan , De Jager Philip L. , Menon Vilas , Schneider Julie A. , Bennett David A. , Hohman Timothy J
Published: April 2024

The cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer’s disease (AD) is not well characterized. In this study, we utilized a single-nucleus RNA sequencing dataset from Dorsolateral Prefrontal Cortex (DLFPC) of 424 donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP) to investigate the effect of 10 VEGF genes (VEGFA, VEGFB, VEGFC, VEGFD, PGF, FLT1, FLT4, KDR, NRP1, andNRP2) on AD endophenotypes. Mean age of death was 89 years, among which 68% were females, and 52% has AD dementia. Negative binomial mixed models were used for differential expression analysis and for association analysis with β-amyloid load, PHF tau tangle density, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated signaling was profiled using CellChat. We discovered prefrontal corticalFLT1expression was upregulated in AD brains in both endothelial and microglial cells. HigherFLT1expression was also associated with worse cross-sectional global cognitive function, longitudinal cognitive trajectories, and β-amyloid load. Similarly, higher endothelialFLT4expression was associated with more β-amyloid load. In contrast to the receptors,VEGFBshowed opposing effects on β-amyloid load whereby higher levels in oligodendrocytes was associated with high amyloid burden, while higher levels in inhibitory neurons was associated with lower amyloid burden. Finally, AD cells showed significant reduction in overall VEGF signaling comparing to those from cognitive normal participants. Our results highlight key changes in VEGF receptor expression in endothelial and microglial cells during AD, and the potential protective role of VEGFB in neurons.
Neuroprotective Efficacy of the Glucocorticoid Receptor Modulator PT150 in the Rotenone Mouse Model of Parkinson’s Disease
Authors: Latham Amanda S. , Rocha Savannah M. , McDermott Casey P. , Reigan Philip , Slayden Richard A. , Tjalkens Ronald B.
Published: April 2024

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder worldwide. Current treatments for PD largely center around dopamine replacement therapies and fail to prevent the progression of pathology, underscoring the need for neuroprotective interventions. Approaches that target neuroinflammation, which occurs prior to dopaminergic neuron (DAn) loss in the substantia nigra (SN), represent a promising therapeutic strategy. The glucocorticoid receptor (GR) has been implicated in the neuropathology of PD and modulates numerous neuroinflammatory signaling pathways in the brain. Therefore, we investigated the neuroprotective effects of the novel GR modulator, PT150, in the rotenone mouse model of PD, postulating that inhibition of glial inflammation would protect DAn and reduce accumulation of neurotoxic misfolded ⍺-synuclein protein. C57Bl/6 mice were exposed to 2.5 mg/kg/day rotenone by intraperitoneal injection for 14 days, immediately followed by oral treatment with 30 mg/kg/day or 100 mg/kg/day PT150 in the 14-day post-lesioning incubation period, during which the majority of DAn loss and α-synuclein (α-syn) accumulation occurs. Our results indicate that treatment with PT150 reduced both loss of DAn and microgliosis in the nigrostriatal pathway. Although morphologic features of astrogliosis were not attenuated, PT150 treatment promoted potentially neuroprotective activity in these cells, including increased phagocytosis of hyperphosphorylated α-syn. Ultimately, PT150 treatment reduced the loss of DAn cell bodies in the SN, but not the striatum, and prohibited intra-neuronal accumulation of α-syn. Together, these data indicate that PT150 effectively reduced SN pathology in the rotenone mouse model of PD.