bluuebunny/crossref_metadata_2025_split huggingface dataset:
75 years of anthropogenic change and its impact on Canadian butterfly taxonomic and phylogenetic diversity
Authors: Lewthwaite J.M.M , Mooers A.Ø 
Published: October 2023

AbstractPrevious studies have documented very little net change in average quadrat-level species richness and phylogenetic diversity. However, although the average remains centered around 0, there is much variation around this mean and many outliers. The relative contribution of anthropogenic drivers (such as climate change or land use change) to these outliers remains unclear. Traits may dictate species responses to these changes, and if relatedness is correlated with trait similarity, then the impacts of anthropogenic change may be clustered on the phylogeny. We build the first regional phylogeny of all Canadian butterfly species in order to examine change in community phylogenetic structure in response to two main documented drivers of change -- climate change and land use change -- across 265 species, 75 years and 96 well-sampled quadrats. We find no evidence that, on average, communities are becoming more or less clustered than one would expect. However, there is much variation depending on the magnitude and type of anthropogenic change occurring within a quadrat. We find that climate change as well as agricultural development is reducing species richness within a quadrat, and these species that are lost tend to be scattered across the phylogeny. However, agricultural abandonment is having the opposite effect: we find increasing species richness in the years immediately following it and decreasing distance between species in quadrats with the highest rates of abandonment, such that the species that colonize these plots tend to be close relatives of those already present and thus contribute little novel phylogenetic diversity to an assemblage. Consistent with previous work, small changes in local species richness may conceal simultaneous change in other facets of biodiversity.
Osteocyte Nicotinic Acetylcholine Receptors Impact Bone Mechanoadaptation in a Sexually Dimorphic Manner
Authors: Mora-Antoinette Macy , Garcia-Ortiz Andrea , Obaji Mariam , Saffari Alexander , Matthews Melia D. , Lewis Karl J. 
Published: October 2023

AbstractRecent evidence suggests acetylcholine has a positive influence on bone mechanotransduction. Indeed, osteocytes express components for nicotinic acetylcholine receptors (nAChRs), which are known for mediating calcium signaling and may impact mechanosensitivity. Here, we use novel fluorescent imaging approaches to provide the first evidence of direct interaction between osteocytes and cholinergic nerve fibers in cortical bone in vivo. Moreover, we show that osteocytes are functional targets of cholinergic signaling for bone mechanoadaptation. We report sexually dimorphic patterns in bone structure and mechanobiology based on nAChR function. In females, osteocyte mechanosensitivity was decreased at small force magnitudes and tissue level deficits were recovered with anabolic loading. In males, osteocyte mechanosensitivity was increased in some groups and anabolic loading had very little effect on tissue architecture. This work establishes a new signaling paradigm wherein osteocytes interface with cholinergic nerves and bone mechanotransduction is regulated by osteocyte cholinergic signaling in a sexually dimorphic way.
RVE based Finite Element Modelling of the Contact Mechanics Between Skin and Indenter
Authors: Pardeshi Rushabh , Dingari Naga Neehar , Rai Beena 
Published: October 2023

AbstractThe nature of contact between human skin and external object (such as medical device, personal care device, fabric and so on) significantly influences the tactile perception and/or the functionality of the object. The contact mechanics depends strongly on the indenter properties and the mechanical properties of skin. Further, the topmost layer i.e., stratum corneum plays the most important role in tactile perception. In this study we use a representative volume element (RVE) based FEM model including the four layers of skin - stratum corneum, epidermis, dermis, and hypodermis - to simulate the contact mechanics between skin and a spherical indenter. The RVE model captures the mechanical properties of the microscopic constituents of the stratum corneum, which is the topmost layer of skin. We found that the RVE model can be used to simulate a variety of stratum corneum conditions (for example, dry and wet stratum corneum) and compositions. Using the RVE model in conjunction with an FEM model, we compute the frictional stress between skin and an indenter, as a function of stratum corneum microstructure, indentation depth, and local coefficient of friction. Both, the RVE model and the contact mechanics model predictions show good qualitative agreement with experimental findings in literature. Such studies will be very useful in in-silico design and optimization of devices that interact with skin. The current framework gives control over several parameters like skin microstructure, indenter or skin geometry and hence can be used to augment/substitute experimental testing.
BloodDDIT4andTRIM13transcript levels mark the early stages of Machado-Joseph disease
Authors: Ferreira Ana F. , Raposo Mafalda , Shaw Emily D. , Vasconcelos João , Kay Teresa , Bettencourt Conceição , Saraiva-Pereira Maria Luiza , Jardim Laura Bannach , do Carmo Costa Maria , Lima Manuela 
Published: October 2023

AbstractMachado-Joseph disease (MJD) is a rare late-onset polyglutamine neurodegenerative disease caused by the expansion of a CAG repeat in theATXN3gene encoding the ataxin- 3 (ATXN3) protein. Several studies have identified changes in the abundance of select transcripts and proteins in blood samples of MJD mutation carriers. Here, we aimed to: 1) identify blood transcriptional changes that could be potential biomarkers of MJD from preclinical to symptomatic disease stages; 2) correlate levels of differentially expressed transcripts in blood of MJD carriers with demographic, genetics, and clinical features; and 3) evaluate whether the identified differential abundance of selected transcripts in blood of MJD subjects is preserved in post-mortem brains of MJD patients. Using real- time quantitative PCR, we observed consistent dysregulation ofDDIT4,TRIM13andP2RY13transcript levels in blood samples of MJD subjects from different disease stages (from preclinical to symptomatic), and of patients from two cohorts with different backgrounds (Azores and Brazil). Importantly, combined bloodDDIT4andTRIM13transcript levels display a very high accuracy to discriminate MJD carriers in preclinical stage, early-stage patients, and patients with more than five years of disease duration from respective controls (AUC=1.00, AUC=0.96, and AUC=0.90, respectively). Moreover, in the combined group of Azorean and Brazilian patients, blood levels ofP2RY13transcript correlate with age at onset, and abundance ofDDIT4andTRIM13transcripts correlate with the CAG repeat size of the expandedATXN3allele. In the subgroup of early-stage Azorean patients, blood levels ofTRIM13transcripts correlate with age at disease onset. Interestingly, abundance of DDIT4, TRIM13 and P2RY13 proteins is also altered in brains of MJD patients. In summary, this work shows that bloodDDIT4andTRIM13transcript levels are potentially blood-based biomarkers of MJD of special usefulness in marking preclinical and early stages of the disease, and points for common dysregulated processes involvingDDIT4,TRIM13andP2RY13in the blood and the brain of MJD subjects.
BBQ methods: Streamlined workflows for Bacterial Burden Quantification in infected cells by confocal microscopy
Authors: Augenstreich Jacques , Shuster Michael , Fan Yongqiang , Lyu Zhihui , Ling Jiqiang , Briken Volker 
Published: October 2023

AbstractAccurate quantification of bacterial burden within macrophages, termed Bacterial Burden Quantification (BBQ), is crucial for understanding host-pathogen interactions. Various methods have been employed, each with strengths and weaknesses. This article addresses limitations in existing techniques and introduces two novel automated methods for BBQ within macrophages based on confocal microscopy data analysis. The first method refines total fluorescence quantification by incorporating filtering steps to exclude uninfected cells, while the second method calculates total bacterial volume per cell to mitigate potential biases in fluorescence-based readouts. These workflows utilize PyImageJ and Cellpose software, providing reliable, unbiased, and rapid quantification of bacterial load. The proposed workflows were validated using Salmonella enterica serovar Typhimurium and Mycobacterium tuberculosis models, demonstrating their effectiveness in accurately assessing bacterial burden. These automated workflows offer valuable tools for studying bacterial interactions within host cells and provide insights for various research applications.
Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar
Authors: Jacobs Ruby V. , Wang Crystal X. , Lozada-Perdomo Fiorella V. , Nguyen Lam , Deere Julia U. , Uttley Hannah A. , Devineni Anita V. 
Published: October 2023

SUMMARYA single sensory cue can elicit diverse behavioral responses. For example, the taste of sugar robustly promotes feeding1, 2but also influences other behaviors, such as altering locomotor patterns to maximize food-finding3, 4or conferring a rewarding value onto associated contexts or cues.5–7Here, we investigate how sweet taste elicits multiple appetitive behaviors inDrosophila. Are different sugar-evoked behaviors coordinately regulated? At what point does the sugar circuit diverge into different pathways that drive distinct behaviors? We first established an optogenetic paradigm to study the effects of sugar taste on locomotion, spatial preference, and associative learning. We then tested how different sugar-evoked behaviors were modulated by internal and external factors, including hunger, diet, or the presence of an aversive taste. Different behaviors were generally modulated in similar ways, but we also observed some differences that reveal selective modulation of specific behavioral pathways. Finally, we investigated where the sugar taste circuit diverges into different behavioral pathways. A recent study identified a sensory-motor circuit comprising five layers of neurons that drives the initiation of feeding in response to sugar.8By individually manipulating each of these neurons, we show that circuits mediating different innate responses to sugar are partially overlapping and begin to diverge at the level of second- and third-order neurons, whereas circuits for innate versus learned behaviors may diverge at the first synapse. Connectomic analyses reveal distinct subcircuits that mediate different behaviors. Together, these studies provide insight into how neural circuits are organized to elicit diverse behavioral responses to a single stimulus.
Astrocyte-specific inhibition of primary cilium functions improves cognitive impairment during neuroinflammation by suppressing A1 astrocyte differentiation
Authors: Muhamad Nor Atiqah , Furukawa Shota , Yuri Shunsuke , Toriyama Michinori , Masutani Kohei , Matsumoto Chuya , Itoh Seiya , Shinagawa Yuichiro , Isotani Ayako , Toriyama Manami , Itoh Hiroshi 
Published: October 2023

AbstractA1 astrocytes play a neurotoxic role in various neurodegenerative diseases. While inhibiting the differentiation of A1 astrocytes can slow disease progression, the mechanisms controlling A1 astrocyte differentiation are largely unknown. The primary cilium is a cellular organelle that receives extracellular signals and regulates cell proliferation, differentiation, and maturation. To elucidate the physiological function of the primary cilium in A1 astrocytes, we utilized primary astrocytes and an inflammation mouse model. We found that the length of the primary cilium was increased in astrocytes, and the inhibition of primary cilium formation inhibited their differentiation into A1 astrocytes. Since mice with systemic ciliogenesis defects exhibit embryonic lethality, the function of the primary cilium in adults has remained largely unclear. Therefore, we established conditional knockout (cKO) mice that specifically inhibit primary cilium function in astrocytes upon drug stimulation. In a neuroinflammation mouse model in which lipopolysaccharide (LPS) was intraperitoneally injected into wild-type mice, increases in A1 astrocyte number and primary cilium length were observed in the brain. In contrast, cKO mice exhibited a reduction in the proportions of A1 astrocytes and apoptotic cells in the brain. Additionally, the novel object recognition (NOR) score observed in the cKO mice was higher than that observed in the neuroinflammation model mice. These results suggest that the primary cilium in astrocytes is essential for A1 astrocyte differentiation, which leads to a decline brain function. We propose that regulating astrocyte-specific primary cilium signalling may be a novel strategy for the suppression of neuroinflammation.
The Subcortical Default Mode Network and Alzheimer’s Disease: A systematic review and Activation Likelihood Estimation Meta-Analysis
Authors: Seoane Sara L , van den Heuvel Martijn , Acebes Ángel , Janssen Niels 
Published: October 2023

AbstractThe default mode network is a central cortical brain network suggested to play a major role in several disorders, and to be particularly vulnerable to the neuropathological hallmarks of Alzheimer’s disease. Subcortical involvement in the default mode network and its alteration in Alzhimer’s disease remains largely unknown. We performed a systematic review, meta-analysis, and empirical validation of the subcortical default mode network in healthy adults, combined with a systematic review, meta-analysis, and network analysis of the involvement of subcortical default mode areas in Alzheimer’s disease. Our results show that, besides the well-known cortical default mode network brain regions, the default mode network consistently includes subcortical regions, namely the thalamus, lobule and vermis IX and right Crus I/II of the cerebellum, and the amygdala. Network analysis also suggests the involvement of the caudate nucleus. In Alzheimer’s disease, we observed a left-lateralized cluster of decrease in functional connectivity which covered the medial temporal lobe and amygdala and showed overlap with the default mode network in a portion covering parts of the left anterior hippocampus and left amygdala. An increase in functional connectivity was also found in the right anterior insula. These results confirm the consistency of subcortical contributions to the default mode network in healthy adults and highlight the relevance of the subcortical default mode network alteration in Alzheimer’s disease.
Impact of digital assistive technologies on the quality of life for people with dementia: A scoping review
Authors: Schneider Charlotte , Nißen Marcia , Kowatsch Tobias , Vinay Rasita 
Published: October 2023

AbstractBackgroundDigital assistive technologies (DATs) have emerged as promising tools to support the daily life of people with dementia (PWD) by offering support in various aspects of daily life. Quality of life (QOL) is an important consideration when discussing the care of PWD in relation to their autonomy. Current research tends to concentrate either on specific categories of DATs, or provide a generic view. Therefore, it would be of essence to provide a review of the different kinds of DATs, and how they contribute to improving QOL for PWD.ObjectiveThis scoping review aimed to review DATs and their impact on QOL for PWD.MethodFor this scoping review a broad literature search was performed in Cochrane, Embase, PubMed, Scopus, and Web of Science, covering scientific literature from January 2013 and May 2023. Screening and data extraction were conducted, followed by quantitative and qualitative analysis using thematic analysis principles and Digital Therapeutics (DTx) Alliance categories for DAT grouping.ResultsThe literature search identified 6’083 records, with 1’056 duplicates. After screening, 4’560 full-texts were excluded, yielding 122 studies of different designs. The DATs were categorized intodigital therapeutics(n=109),patient monitoring(n=30),digital diagnostics(n=2),care support(n=2), andhealth system clinical software (n=1). These categories were identified to impact various aspects of QOL: preserving autonomy, engagement, and social interaction, health monitoring and promotion, improving activities of daily living, improving cognition, maintaining dignity, managing behavioral and psychological symptoms of dementia (BPSD), and safety/surveillance.ConclusionsVarious DATs offer extensive support, elevating the QOL of PWD.Digital therapeuticsare predominantly used for aging-in-place and independent living through assistance with daily tasks. Future research should focus on less-represented DHT categories, such ascare support, health & wellnessorsoftwaresolutions. Observing ongoing DAT developments and their long-term effects on QOL remains essential.Strengths and limitations of this studyThe study conducted an extensive search across five electronic databases spanning a decade to identify relevant literature on DATs and their impact on the QOL for PWD.By excluding conference proceedings, book chapters, pilot, and feasibility studies, the review might have missed ongoing or planned research that could offer insights into different DATs or QOL impacts.While the scoping review approach allowed for a broad overview, it didn’t assess the quality of included studies or intervention effectiveness, potentially introducing bias and limiting in-depth analysis.The study’s emphasis on patient-facing DATs could have introduced bias, highlightingdigital therapeuticsin the included literature while potentially overlooking other assistive technology categories.
Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States
Authors: Perofsky Amanda C , Huddleston John , Hansen Chelsea , Barnes John R , Rowe Thomas , Xu Xiyan , Kondor Rebecca , Wentworth David E , Lewis Nicola , Whittaker Lynne , Ermetal Burcu , Harvey Ruth , Galiano Monica , Daniels Rodney Stuart , McCauley John W , Fujisaki Seiichiro , Nakamura Kazuya , Kishida Noriko , Watanabe Shinji , Hasegawa Hideki , Sullivan Sheena G , Barr Ian G , Subbarao Kanta , Krammer Florian , Bedford Trevor , Viboud Cécile 
Published: October 2023

AbstractInfluenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997—2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection dynamics, presumably via heterosubtypic cross-immunity.Impact statement:Antigenic drift in influenza’s major surface proteins – hemagglutinin and neuraminidase – contributes to variability in epidemic magnitude across seasons but is less influential than subtype interference in shaping annual outbreaks.
Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome
Authors: Sanfilippo Piero , Kim Alexander J. , Bhukel Anuradha , Yoo Juyoun , Mirshahidi Pegah S. , Pandey Vijaya , Bevir Harry , Yuen Ashley , Mirshahidi Parmis S. , Guo Peiyi , Li Hong-Sheng , Wohlschlegel James A. , Aso Yoshinori , Lawrence Zipursky S. 
Published: October 2023

SummaryNeurons express different combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here we use epitope tagged endogenous NR subunits, expansion light-sheet microscopy, and EM connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determines patterns of synaptic inputs. In support of this model, we identify a transmembrane protein associated selectively with a subset of spatially restricted synapses and demonstrate through genetic analysis its requirement for synapse formation. We propose that mechanisms which regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.
A neurocomputational account of the link between social perception and social action
Authors: Bas Lisa M. , Roberts Ian D. , Hutcherson Cendri A. , Tusche Anita 
Published: October 2023

AbstractPeople selectively help others based on perceptions of their merit or need. Here, we develop a neurocomputational account of how these social perceptions translate into social choice. Using a novel fMRI social perception task, we show that both merit and need perceptions recruited the brain’s social inference network. A behavioral computational model identified two non-exclusive mechanisms underlying variance in social perceptions: a consistent tendency to perceive others as meritorious/needy (bias) and a propensity to sample and integrate normative evidence distinguishing high from low merit/need in other people (sensitivity). Variance in people’s merit (but not need) bias and sensitivity independently predicted distinct aspects of altruism in a social choice task completed months later. An individual’s meritbiaspredictedcontext-independentvariance in people’s overall other-regard during altruistic choice, biasing people towards prosocial actions. An individual’s meritsensitivitypredictedcontext-sensitivediscrimination in generosity towards high and low merit recipients by influencing other-regard and self-regard during altruistic decision-making. This context-sensitive perception-action link was associated with activation in the right temporoparietal junction. Together, these findings point towards stable, biologically based individual differences in perceptual processes related to abstract social concepts like merit, and suggest that these differences may have important behavioral implications for an individual’s tendency toward favoritism or discrimination in social settings.