bluuebunny/crossref_metadata_2025_split huggingface dataset:
LGBTQ+ Affirming Care May Increase Awareness and Understanding of Undetectable=Untransmittable among Midlife and Older Gay and Bisexual Men in the US South
Authors: McKay Tara , Akré Ellesse-Roselee , Henne Jeff , Conway Adam , Gothelf Isabel , Kari Nitya 
Published: June 2022

AbstractOne of the most significant innovations in HIV prevention is the use of HIV treatment to prevent HIV transmission. This information has been disseminated as the “Undetectable = Untransmittable” (U=U) message. Despite evidence of effectiveness, U=U awareness, belief, and understanding remains limited in some communities. In this study we examine whether having an LGBTQ affirming healthcare provider increases U=U awareness, belief, and understanding among midlife and older gay and bisexual men in the US South, an understudied and underserved population and region where new HIV infections are increasing. We use data from the Vanderbilt University Social Networks Aging and Policy Study (VUSNAPS) on sexual minority men aged 50 to 76 from four Southern US states collected in 2020-2021. We find that only one in four men report prior awareness of U=U, but awareness is higher among HIV negative and HIV positive men who have an LGBTQ affirming provider. Having an affirming provider significantly increases U=U belief and understanding, improves risk perception accuracy, and increases the likelihood of having ever tested for HIV among HIV negative men. Improving access to LGBTQ affirming healthcare may improve U=U awareness, belief, and understanding, which could help to curb HIV transmission in the US South.
Semantic novelty modulates neural responses to visual change across the human brain
Authors: Nentwich Maximilian , Leszczynski Marcin , Russ Brian E. , Hirsch Lukas , Markowitz Noah , Sapru Kaustubh , Schroeder Charles E. , Mehta Ashesh , Bickel Stephan , Parra Lucas C 
Published: June 2022

AbstractOur continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.
Phylogenomic Analysis of Protein-Coding Genes Resolves Complex Gall Wasp Relationships
Authors: Hearn Jack , Gobbo Erik , Nieves-Aldrey José Luis , Branca Antoine , Nicholls James A. , Koutsovoulos Georgios , Lartillot Nicolas , Stone Graham N. , Ronquist Fredrik 
Published: June 2022

AbstractThe phylogeny of gall wasps (Cynipidae) and their parasitic relatives has attracted considerable attention in recent years. The family is now widely recognized to fall into thirteen natural lineages, designated tribes, but the relationships among them have remained elusive. This has stymied any progress in understanding how cynipid gall inducers evolved from insect parasitoids, and what role inquilinism (development as a herbivore inside galls induced by other cynipids) might have played in this transition. A recent analysis of ultraconserved elements (UCEs) represents the first attempt at resolving these questions using phylogenomics. Here, we present the first analysis based on protein-coding sequences from genome and transcriptome assemblies. To address potential problems due to model misfit, we focus on models that accommodate site-specific amino-acid profiles and that are less sensitive than standard models to long-branch attraction. Our results show that the Cynipidae as previously circumscribed are not monophyletic. Specifically, the Paraulacini and a clade formed by Diplolepidini + Pediaspidini both fall outside a core clade (Cynipidae s. str.), which is more closely related to Figitidae. This result is robust to the exclusion of long-branch taxa that could potentially mislead the analysis, and it is consistent with the UCE analysis. Given this, we propose that the Cynipidae be divided into three families: the Paraulacidae, Diplolepididae and Cynipidae (s. str.). Our results suggest that the Eschatocerini are the sister group of the remaining Cynipidae (s. str.). Within the latter, our results are consistent with the UCE analysis but place two additional tribes: (1) the Aylacini (s. str.), more closely related to the oak gall wasps (Cynipini) and some of their inquilines (Ceroptresini) than to other herb gallers (Aulacideini and Phanacidini); and (2) the Qwaqwaiini, likely the sister group to Synergini (s. str.) + Rhoophilini. Several alternative scenarios for the evolution of cynipid life histories are compatible with the relationships suggested by our analysis, but all are complex and require multiple shifts between parasitoids, inquilines and gall inducers. Linking the different types of life-history transitions to specific genomic signatures may be one of the best ways of differentiating among these alternative scenarios. Our study represents the first step towards enabling such analyses.
In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa
Authors: Su Jing , She Kaiqin , Song Li , Jin Xiu , Li Ruiting , Zhao Qinyu , Xiao Jianlu , Chen Danian , Cheng Hui , Lu Fang , Wei Yuquan , Yang Yang 
Published: June 2022

AbstractRetinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the β-domain of the phosphodiesterase 6 (Pde6b) gene are among the most identified causes of autosomal recessive RP. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivery to postmitotic photoreceptors is used to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrects Pde6b mutation with up to 37.41% efficiency at the DNA level and up to 91.95% efficiency at the cDNA level, restores PDE6B expression, preserves photoreceptors and rescues visual function. RNA-seq reveals upregulation of genes associated with phototransduction and photoreceptor survival. Our data demonstrate that base editing is a potential gene therapy that could provide durable protection against RP.
Cable-free brain imaging with miniature wireless microscopes
Authors: Wang Yangzhen , Ma Zhongtian , Li Wenzhao , Su Feng , Wang Chong , Xiong Wei , Li Changhui , Zhang Chen 
Published: June 2022

AbstractThe invention of the miniaturized microscope has enabled neuroscientists to investigate neural mechanisms in freely moving mice. A lot of efforts have been made to optimize performance of the miniaturized microscope. However, the tethered cables limit the ability of mini-microscope systems to record neural activity from multiple mice simultaneously. Here, we present a wireless mini-microscope (wScope) that enables both real-time remote control and data preview during animal behavior; this design also supports simultaneous recording from up to 8 mice. The wScope has a mass of 2.7 g and a maximum frame rate of 25 Hz at 750 μm by 450 μm field of view with 1.8 μm resolution. We validated the wScopes in video-recording of the cerebral blood flow (CBF) and the activity of neurons in the primary visual cortex (V1) of different mice. The wScope provides a powerful tool for brain imaging of free moving animals, including large primates, in their much larger spaces and more naturalistic environments.
Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast
Authors: Sultana Sarmin , Abdullah Mudabir , Li Jianhui , Hochstrasser Mark , Kachroo Aashiq H. 
Published: June 2022

AbstractYeast and humans share thousands of genes despite a billion years of evolutionary divergence. While many human genes can functionally replace their yeast counterparts, nearly half of the tested shared genes cannot. For example, most yeast proteasome subunits are humanizable, except subunits comprising the β-ring core, including β2 (HsPSMB7). We developed a high-throughput pipeline to humanize yeast proteasomes by generating a large library of Hsβ2 mutants and screening them for complementation of yeast β2 (ScPup1). Variants capable of replacing ScPup1 included (1) those impacting local protein-protein interactions (PPIs), with most affecting interactions between the β2 C-terminal tail and the adjacent β3 subunit, and (2) those affecting β2 proteolytic activity. Exchanging the full-length tail of human β2 with that of ScPup1 enabled complementation. Moreover, wild-type human β2 replaced yeast β2 if the adjacent human β3 subunit was also provided. Unexpectedly, yeast proteasomes bearing a catalytically inactive HsPSMB7-T44A variant blocking precursor autoprocessing were viable, suggesting an intact propeptide stabilizes late assembly intermediates. Our data reveal roles for specific PPIs governing functional replaceability across vast evolutionary distances.
Route-dependent spatial engram tagging in mouse dentate gyrus
Authors: Wilmerding Lucius K. , Kondratyev Ivan , Ramirez Steve , Hasselmo Michael E. 
Published: June 2022

SUMMARYThe dentate gyrus (DG) of hippocampus is hypothesized to act as a pattern separator that distinguishes between similar input patterns during memory formation and retrieval. Sparse ensembles of DG cells associated with learning and memory, i.e. engrams, have been labeled and manipulated to recall novel context memories. Functional studies of DG cell activity have demonstrated the spatial specificity and stability of DG cells during navigation. To reconcile how the DG contributes to separating global context as well as individual navigational routes, we trained mice to perform a delayed-non-match-to-position (DNMP) T-maze task and labeled DG neurons during performance of this task on a novel T-maze. The following day, mice navigated a second environment: the same T-maze, the same T-maze with one route permanently blocked but still visible, or a novel open field. We found that the degree of engram reactivation across days differed based on the traversal of maze routes, such that mice traversing only one arm had higher ensemble overlap than chance but less overlap than mice running the full two-route task. Mice experiencing the open field had similar ensemble sizes to the other groups but only chance-level ensemble reactivation. Ensemble overlap differences could not be explained by behavioral variability across groups, nor did behavioral metrics correlate to degree of ensemble reactivation. Together, these results support the hypothesis that DG contributes to spatial navigation memory and that partially non-overlapping ensembles encode different routes within the context of different environments.HighlightsImmediate-early-gene labeling strategy revealed spatial navigation ensembles in DGSub-ensembles encode separate maze routes within a larger task contextEnsemble reactivation does not correlate with behavioral variables
Across atoms to crossing continents: application of similarity measures to biological location data
Authors: Schuhmann Fabian , Ryvkin Leonie , McLaren James D. , Gerhards Luca , Solov’yov Ilia A. 
Published: June 2022

AbstractBiological processes involve movements across all measurable scales. Similarity measures can be applied to compare and analyze these movements but differ in how differences in movement are aggregated across space and time. The present study reviews frequently-used similarity measures, such as the Hausdorff distance, Frechet distance, Dynamic Time Warping, and Longest Common Subsequence, jointly with several measures less used in biological applications (Wasserstein distance, weak Fréchet distance, and Kullback-Leibler divergence), and provides computational tools for each of them that may be used in computational biology. We illustrate the use of the selected similarity measures in diagnosing differences within two extremely contrasting sets of biological data, which, remarkably, may both be relevant for magnetic field perception by migratory birds. Specifically, we assess and discuss cryptochrome protein conformational dynamics and extreme migratory trajectories of songbirds between Alaska and Africa. We highlight how similarity measures contrast regarding computational complexity and discuss those which can be useful in noise elimination or, conversely, are sensitive to spatiotemporal scales.
Quantifying the number of translatable transcripts through the use of OMICs involved in post-transcriptional regulation
Authors: Ochoteco Asensio Juan , Kleinjans Jos , Caiment Florian 
Published: June 2022

AbstractTranscriptomics is nowadays frequently used as an analytical tool to study the extent of cell expression changes between two phenotypes or between different conditions. However, an important portion of the significant changes observed in transcriptomics at the gene level is usually not consistently detected at the protein level by proteomics. This poor correlation between the measured transcriptome and proteome is probably mainly due to post-transcriptional regulation, among which miRNA and circRNA have been proposed to play an important role. Therefore, since both miRNA and circRNA are also quantified by transcriptomics, we proposed to build a model taking those factors into account to estimate, for each transcript, the fraction of transcripts that would be available for translation. Using a dataset of cells exposed to diverse compounds, we evaluated how our model was able to improve the correlation between the assessed transcriptome and proteome expression level. The results show that the model improved the correlation for a subset of genes, probably due to the regulation of different miRNAs across the genome.
Hippocampal 4-Hz oscillations emerge during stationary running in a wheel and are resistant to medial septum inactivation
Authors: de Lima Ivan Alisson Cavalcante Nunes , Belchior Hindiael 
Published: June 2022

ABSTRACTRecent studies described 2-4 Hz oscillations in the hippocampus of rats performing stationary locomotion on treadmills and other apparatus. Since the 2-4 Hz rhythm shares common features with hippocampal theta (5-12 Hz) oscillations - such as a positive running speed-amplitude relationship and modulation of spiking activity - many have questioned whether these rhythms are related or independently generated. To answer this question, we analyzed local field potentials (LFP) and spiking activity from the dorsal CA1 of rats executing a spatial alternation task and running for ∼15 s in a wheel during the intertrial intervals both before and after muscimol injection into the medial septum. We observed 4-Hz oscillations during wheel runs, but not during maze runs. The 4-Hz amplitude positively correlated with wheel speed and negatively with maze speed. Also, the amplitude of 4-Hz and theta oscillations were inversely related. Medial septum inactivation abolished hippocampal theta but preserved 4-Hz oscillations. It also affected the entrainment of pyramidal cells and interneurons by 4-Hz rhythmic activity. In all, these results dissociate the underlying mechanism of 4-Hz and theta oscillations in the rat hippocampus.Highlights4-Hz oscillations emerge in the rat hippocampus during wheel running and correlate with speed4-Hz and theta amplitude are inversely correlated4-Hz oscillations are resistant to medial septum inactivationRhythmic discharge of interneurons and pyramidal cells at 4-Hz are reduced by medial septum inactivationIn briefLima and Belchior tested whether the pharmacological inactivation of the medial septum affects hippocampal 4-Hz oscillations associated with stationary running. They found that septal inactivation preserved 4-Hz oscillations while abolished theta, which dissociate the underlying mechanisms of these rhythms in the rat hippocampus.
Resource-Rational Account of Sequential Effects in Human Prediction
Authors: Prat-Carrabin Arthur , Meyniel Florent , da Silveira Rava Azeredo 
Published: June 2022

AbstractAn abundant literature reports on ‘sequential effects’ observed when humans make predictions on the basis of stochastic sequences of stimuli. Such sequential effects represent departures from an optimal, Bayesian process. A prominent explanation posits that humans are adapted to changing environments, and erroneously assume nonstationarity of the environment, even if the latter is static. As a result, their predictions fluctuate over time. We propose a different explanation in which sub-optimal and fluctuating predictions result from cognitive constraints (or costs), under which humans however behave rationally. We devise a framework of costly inference, in which we develop two classes of models that differ by the nature of the constraints at play: in one case the precision of beliefs comes at a cost, resulting in an exponential forgetting of past observations, while in the other beliefs with high predictive power are favored. To compare model predictions to human behavior, we carry out a prediction task that uses binary random stimuli, with probabilities ranging from .05 to .95. Although in this task the environment is static and the Bayesian belief converges, subjects’ predictions fluctuate and are biased toward the recent stimulus history. Both classes of models capture this ‘attractive effect’, but they depart in their characterization of higher-order effects. Only the precision-cost model reproduces a ‘repulsive effect’, observed in the data, in which predictions are biased away from stimuli presented in more distant trials. Our experimental results reveal systematic modulations in sequential effects, which our theoretical approach accounts for in terms of rationality under cognitive constraints.
Immune evasion impacts the selective landscape of driver genes during tumorigenesis
Authors: Gourmet Lucie , Sottoriva Andrea , Secrier Maria , Zapata Luis 
Published: June 2022

AbstractCarcinogenesis is an evolutionary process fueled by the interplay of somatic mutations and the local microenvironment. In recent years, hundreds of cancer related genes have been discovered using cancer cohorts. However, these cohorts are heterogenous mixtures of different molecular phenotypes, which hampers the identification of driver genes associated to a specific cancer hallmark or microenvironment. Here, we compared the landscape of positively selected somatic mutations in immune-escaped (escape+) versus non-escaped (escape-) tumors. We applied the ratio of non-synonymous to synonymous mutations (dN/dS) to 9896 individuals from 31 primary tumor tissues from the Cancer Genome Atlas (TCGA) separated by escape status. Altogether, we found 85 driver genes, including 27 and 16 novel driver genes in escape- and escape+ tumors, respectively. Overall, driver dN/dS of escape+ tumors (dN/dS=1.23) was significantly lower and closer to neutrality than driver dN/dS of escape-tumors (dN/dS=1.62), suggesting a relaxation of positive selection in driver genes, a relaxation of negative selection on immunogenic driver sites, or a combination of both fueled by immune escape. We also found that the proportion of unique sites mutated in escape+ tumors is almost double than in escape-tumors, and that immune evasion allows for a more diverse repertoire of mutational signatures. We also identified that strong immunoediting in the absence of escape leads to a better overall survival in tumors enriched by an inflamed phenotype. Ultimately, our findings reveal differences in the evolutionary strategies used by cancer cells to establish tumorigenesis and highlight the need for better patient stratification to develop tailored treatments based on molecular targets.
Ancestral sex-role plasticity facilitates the evolution of same-sex sexual behaviour
Authors: Mizumoto Nobuaki , Bourguignon Thomas , Bailey Nathan W. 
Published: June 2022

AbstractRecent attempts to explain the evolutionary prevalence of same-sex sexual behaviour (SSB) have focused on the role of indiscriminate mating. However, in many cases, SSB involves plastically adjusting sex roles to achieve successful courtship or pairing. To evaluate this overlooked factor, we tested whether ancestral sex-role plasticity facilitated the evolution of SSB in the termite Reticulitermes speratus. Male termites follow females in paired ‘tandems’ before mating, and movement patterns are sexually dimorphic. Adaptive same-sex tandems occur in both sexes. We show that in such cases, one partner adopts the other sex’s movement patterns, resulting in behavioural dimorphism. Data-based simulations confirmed that this socially-cued plasticity contributes to pair maintenance because dimorphic movements improve reunion success upon accidental separation. Phylogenetic analysis indicated that the ancestors of modern termites lack consistent sex roles during pairing, indicating that R. speratus inherited the plasticity from the ancestor. Socio-environmental induction of ancestral behavioural potential may be of widespread importance to the evolutionary maintenance of SSB.
Changes in benthic and pelagic production interact with warming to drive responses to climate change in a temperate coastal ecosystem
Authors: Audzijonyte Asta , Delius Gustav , Stuart-Smith Rick D. , Novaglio Camilla , Edgar Graham J. , Barrett Neville S. , Blanchard Julia L. 
Published: June 2022

AbstractChanging sea temperatures and primary productivity are rapidly altering marine ecosystems, but with considerable uncertainty in our understanding of the relative importance of these drivers and how their interactions may affect fisheries yield through complex food webs. Such outcomes are more difficult to predict for shallow coastal ecosystems than those in pelagic and shelf habitats, because coastal food webs are fuelled by a combination of separate pelagic and benthic energy pathways. Using long-term, empirical field data, we developed a novel multispecies size spectrum model for shallow coastal reefs. We include size-structured benthic and pelagic resources and trophic structures, allowing us to explore potential climate change scenarios that involve varying combinations of warming with changes in benthic and pelagic resources. Our model predicts that changes in resource levels will have much stronger impacts on fish biomass and yields than changes driven by physiological responses to temperature. Under increased plankton abundance, species in all trophic groups were predicted to increase in biomass, average size and yields. By contrast, changes in benthic resource produced variable responses across coastal trophic groups. Increased benthic resource led to increasing benthivorous and piscivorous fish biomass, yields and mean body sizes, but decreases in herbivores and planktivores. When resource changes were combined with warming seas, physiological responses generally decreased species’ biomass and yields. Our results suggest that the source, size and abundance of primary and secondary producers are critical to understanding impacts of warming seas on coastal fish communities. Understanding changes in benthic production and its implications for coastal fisheries requires urgent attention. Our modified size spectrum model provides a framework for further study of benthic and pelagic energy pathways that can be easily adapted to other ecosystems.