bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal dynamics of viral fitness and the adaptive immune response in HCV infection
Authors: Walker Melanie R. , Leung Preston , Keoshkerian Elizabeth , Pirozyan Mehdi R. , Lloyd Andrew R. , Luciani Fabio , Bull Rowena A. 
Published: September 2024

AbstractNumerous studies have shown that viral variants that elude the host immune response may incur a fitness expense, diminishing the survival of the viral strain within the host, and the capacity of the variant to survive future transmission events. However, this generic definition can be further divided into two categories where intrinsic fitness describes the viral fitness without the influence of any immune pressure and effective fitness considers both intrinsic fitness with the influence of host immune pressure. Furthermore, co-occurring mutations outside the epitope regions targeted by the immune response may increase or decrease the likelihood of survival of the variant (known as epistasis). Analysis of viral fitness and epistasis over the non-structural protein regions is lacking for hepatitis C virus (HCV). Here, using a rare cohort of subjects very recently infected with HCV, we build upon our prior investigations by integrating mathematical modelling and experimental data to examine the interplay between the evolving transmitted/founder (T/F) viruses, the adaptive immune response, viral fitness, and co-occurring mutations. We show that viral fitness decreases during the first 90 days post-infection (DPI) associated with the magnitude of CD8+ T-cell responses and the initial level of diversification. Thereafter, viral fitness rebounds in a complex pattern of evolution characterized by multiple sets of co-occurring mutations. Finally, we show that an early and strong CD8+ T-cell response in the absence of neutralizing antibodies (nAbs) imposes a strong selective force on the T/F virus population, enabling the virus to escape and establish chronic infection. Understanding these dynamics is highly relevant for HCV vaccine design and supports a vaccine strategy that induces broad immunity targeting both T and B cell responses.
Single cone photoreceptors experience global image statistics through gaze shifts
Authors: Morimoto Takuma , Wang Luna , Amano Kinjiro , Foster David H. , Nascimento Sérgio M. C. 
Published: September 2024

AbstractOur visual experience does not merely reflect a static view of the world but is a dynamic consequence of our actions, most notably our continuously shifting gaze. These shifts determine the spectral diet of any individual cone photoreceptor. The aim of this study was to characterize that diet and its relationship to scene adaptation. Gaze shifts were recorded from observers freely viewing scenes outdoors for five minutes. Hyperspectral images of the scenes were also recorded from the observer’s eye position. As a control, gaze shifts were also recorded from observers viewing the images on a computer-controlled display in the laboratory. From the hyperspectral data, spatially local histograms of estimated excitations in long-, medium-, and short-wavelength-sensitive cones were accumulated over time at different retinal locations. A global illuminant change was then introduced to test how well local retinal adaptation discounted its effects. The results suggest that over short periods individual cones tend to experience the statistics of full scenes, with local adaptation compensating for illumination changes almost as well as global adaptation. This compensation may help to maintain our stable local perception of scene colour despite changes in scene illumination.
Nicotine interacts with DNA lesions induced by alpha radiation which may contribute to erroneous repair in human lung epithelial cells
Authors: Boroumand Nadia , Baghdissar Carol , Elihn Karine , Lundholm Lovisa 
Published: September 2024

ABSTRACTPurposeEpidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood.Materials and methodsBronchial epithelial BEAS-2B cells were either pre-treated with 2 μM nicotine during 16 h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses.ResultsLess γH2AX foci were detected at 1 h after alpha radiation exposure (1–2 Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1 h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27 h after irradiation. Although nicotine did not alter G2 arrest at 24 h, it assisted in cell cycle progression at 48 h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1β (4 Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci.ConclusionsThis study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.
Aging-associated vacuolation of multi-ciliated cells in the distal mouse oviduct reflects unique cell identity and luminal microenvironment
Authors: Harwalkar Keerthana , Yamanaka Nobuko , Pacis Alain S , Zhao Selina , Teng Katie , Pitman Warwick , Taskar Mitaali , Lynn Vera , Thornton Alex Frances , Ford Matthew J , Yamanaka Yojiro 
Published: September 2024

ABSTRACTThe female reproductive organs present with the earliest aging characteristics, such as a decline in fertility and estrous cyclicity. While age-related changes in the ovary are well-documented, it is unclear if any age-associated changes occur in the other female reproductive organs, such as the oviduct/fallopian tube. The recent recognition of the distal end of the fallopian tube as the tissue of origin of high-grade serous tubal ovarian carcinomas (HGSCs), and that its patient demographic is strongly biased to postmenopausal women, motivated us to investigate age-associated changes in this organ.At the distal end of aged oviducts in mice, we found vacuolated multi-ciliated cells (MCCs) with a severely apically displaced and deformed nucleus. This phenotype was unique to the distal oviduct epithelium –infundibulum (INF) and ampulla (AMP). Ovariectomy did not affect the timeline of MCC vacuolation, suggesting little involvement of ovulation and hormonal regulation. MCC vacuolation was induced in hypoxia or hydroxyurea treatments inin vitroorganotypic culture of all oviduct regions, not limited to the INF/AMP epithelium. This suggests high oxygen demand in MCCs, compared to other cell types, and a uniquely stressed INF/AMP epithelial microenvironmentin vivo. We found that the blood circulation of INF/AMP depended on the ovarian artery, different from the rest of the oviduct epithelium and its circulation declined along with ovarian activities. We conclude that a decline in local blood circulation and distinct cellular identity of the INF/AMP epithelium caused age-associated MCC vacuolation, reflecting its mild, chronically stressed microenvironment.
Sex differences in contextual fear expression are associated with altered medial prefrontal cortex activity
Authors: Vazquez Katherine , Parsons Ryan G. 
Published: September 2024

AbstractUnderstanding the neural basis of fear expression in rodents has implications for understanding pathological fear responses that characterize posttraumatic stress disorder. Even though posttraumatic stress disorder is more common in females, little is known about the neural circuit interactions supporting fear expression in female rodents. In this study, we were interested in determining whether neural activity associated with the expression of contextual fear differed between males and females within the projections from the medial prefrontal cortex to the ventrolateral periaqueductal gray, and in the medial prefrontal cortex in neurons that do not project to the periaqueductal gray. We infused a viral retrograde tracer into the ventrolateral periaqueductal gray in male and female rats and trained them in a contextual fear conditioning task. The following day rats were re-exposed to the conditioning context and were sacrificed shortly thereafter. Neural activity was measured using EGR1 immunofluorescence. The behavioral results showed that males exhibited higher levels of freezing during the context test than females. Male rats that underwent training and testing showed an increase in the proportion of viral infected cells that express EGR1 in the PL compared to rats that had only received context exposure. Trained female rats were not different than controls, however a direct comparison between sexes was not different. In cells not labeled by the tracer, males showed higher levels of fear-induced EGR1 expression in the prelimbic cortex than females. Conversely, females showed higher levels of EGR1 expression in the infralimbic cortex following testing as compared to males. These results suggest that sex differences in the expression of contextual fear may involve differences in the relative activity levels of the prelimbic and infralimbic cortex.
Stronger premicrosaccadic sensitivity enhancement for dark contrasts in the primate superior colliculus
Authors: Wu Wenbin , Hafed Ziad M. 
Published: September 2024

AbstractMicrosaccades are associated with enhanced visual perception and neural sensitivity right before their onset, and this has implications for interpreting experiments involving the covert allocation of peripheral spatial attention. However, the detailed properties of premicrosaccadic enhancement are not fully known. Here we investigated how such enhancement in the superior colliculus depends on luminance polarity. Rhesus macaque monkeys fixated a small spot while we presented either dark or bright image patches of different contrasts within the recorded neurons’ response fields. Besides replicating premicrosaccadic enhancement of visual sensitivity, we observed stronger enhancement for dark contrasts. This was especially true at moderate contrast levels (such as 10-20%), and it occurred independent of an individual neuron’s preference for either darks or brights. On the other hand, postmicrosaccadic visual sensitivity suppression was similar for either luminance polarity. Our results reveal an intriguing asymmetry in the properties of perimicrosaccadic modulations of superior colliculus visual neural sensitivity.
Effects of fasting on heat-stressed broiler chickens: part I- growth performance, meat quality, gut histomorphological and microbial responses
Authors: Ahmed Tanvir , Hashem Md. Abul , Afrin Afifa , Lahiry Ankon , Rahman Shahina , Bungo Takashi , Das Shubash Chandra 
Published: September 2024

AbstractThe current study aimed to optimize the fasting duration in order to mitigate the detrimental effects of heat stress on broilers raised in hot and humid climatic environments. A total of 500 broiler DOCs were assigned to five distinct treatment groups: Tₒ= Non-fasted controlled temperature (24-26℃) (NF-CT), T1= Non-fasted heat stressed (30-38℃) (NF-HS), T2= 6 hours fasted heat stressed (6-h FHS), T3= 8 hours fasted heat stressed (8-h FHS), and T4= 10 hours fasted heat stressed (10-h FHS). Each treatment was replicated five times, with 20 birds in each replicate group. As expected, the birds in NF-CT group showed significantly better performances for all the growth parameters, although birds who fasted for 8-h under heat stress exerted better growth and FCR in comparison to the other HS groups. Fasting of birds under heat stress significantly showed the lowest mortality. Like the NF-CT group, birds in 8-h FHS achieved significantly higher dressing percentage, breast meat, liver yields, and the lowest abdominal fat. Fasting for 8- and 10-h significantly increased breast meat pH and water holding capacity and thus reduced cooking loss. Fasting also improved the breast meat color quality by increasing redness (a*) and reducing the hue angle values comparable with the NF-CT group. A significantly upward trend in villi height (VH), width (VW) and crypt depth (CD) of gut segments was also observed in the birds of the 8-h FHS group. Total bacterial and coliform counts in cecum contents were reduced significantly with the increase in the fasting period. Benefit-cost analysis showed better profitability in the 8-h FHS group than other HS groups. Taken altogether, it can be concluded that broiler chicken exposed to 8-h fasting period is an effective approach to mitigate heat stress under hot and humid climatic conditions.
Preventing surgery induced immune suppression and metastases by inhibiting PI3K-gamma signalling in Myeloid-Derived Suppressor Cells
Authors: Angka Leonard , Tennakoon Gayashan , Cook David P. , Martel Andre B. , Market Marisa , de Souza Christiano Tanese , Cummins Emma , Samudio Ismael , Kekre Natasha , Ardolino Michele , Vanderhyden Barbara , Kennedy Michael A. , Auer Rebecca C. 
Published: September 2024

AbstractMyeloid derived suppressor cells (MDSCs) have a dominating presence in the postoperative period and mediate the suppression of Natural Killer (NK) cells and promotion of cancer metastases after surgery. However, their functional characteristics and effect on cellular immunity after surgery have not been comprehensively investigated. Here, we characterize the expansion of surgery-induced (sx) MDSCs via multi-colour flow cytometry, single-cell RNA sequencing, and functionalex vivoNK cell suppression assays. We then screened a small molecule library using our sx-MDSC:NK cell suppression assay to identify compounds that could inhibit sx-MDSCs. These studies provide evidence that PI3K-γ signalling is upregulated in sx-MDSCs and blockade with PI3K-γ specific inhibitors attenuates NK cell suppression in humans and mice and reduces postoperative metastases in murine models. Upregulated PI3K-γ in sx-MDSCs is a potential pathway amenable to therapeutic targeting in the postoperative period.One Sentence SummaryThe suppressive mechanisms of surgery-induced myeloid derived suppressor cells use PI3K signalling and are amenable to PI3K-gamma specific inhibitors.
Landscape-wide metabarcoding of the invasive bumblebee(Bombus terrestris)shows interactions among the gut microbiome and pollenbiome
Authors: Haque Sabrina , Gamage Hasinika KAH , Kardum Hjort Cecilia , Ponton Fleur , Encinas-Viso Francisco , Paulsen Ian T , Dudaniec Rachael Y 
Published: September 2024

AbstractMany species of social insects introduced to regions beyond their native ranges have become highly invasive. The introduction of the eusocial European buff-tailed bumblebee,Bombus terrestris, to the island of Tasmania (Australia) ∼30 years ago is of concern due to its ecological impacts and its potential to spill over pathogens to native bees or commercially important honeybees. The health ofB. terrestrisis intricately connected with its gut microbiome and diet; however, environmental variables may also interact, particularly during invasion into novel environments. Using landscape-wide sampling and a metabarcoding approach to characterize the gut bacteria (16S rRNA) and diet composition from foraged pollen (ITS2: floristic diversity of pollen baskets), this study investigates how the gut microbiota ofB. terrestrisworkers is affected by nutritional diversity (‘pollenbiome’) and environmental variation across diverse landscapes of its invasive range in Tasmania. Gut bacterial community composition and diversity were significantly predicted by site annual precipitation and percentage of pasture. Further, a positive interaction between site annual precipitation and site annual temperature significantly predicted gut bacterial diversity. The interaction effect of pollen diversity and average summer wind velocity was also significantly and positively related to gut bacterial diversity. Following comparison of Akaike information criterion (AIC) and sum of weights, the percentage of pasture was identified as the most strongly weighted variable, which, along with pollen diversity, had a negative impact on gut bacterial diversity. These insights help to uncover how environmental interactions affect the gut microbiome ofB. terrestrisin an invaded landscape with novel nutritional resources. This knowledge contributes to understanding the factors that predict the spread and persistence of invasive bumblebees.
Novae: a graph-based foundation model for spatial transcriptomics data
Authors: Blampey Quentin , Benkirane Hakim , Bercovici Nadège , André Fabrice , Cournède Paul-Henry 
Published: September 2024

AbstractSpatial transcriptomics is advancing molecular biology by providing high-resolution insights into gene expression within the spatial context of tissues. This context is essential for identifying spatial domains, enabling the understanding of micro-environment organizations and their implications for tissue function and disease progression. To improve current model limitations on multiple slides, we have designed Novae (https://github.com/MICS-Lab/novae), a graph-based foundation model that extracts representations of cells within their spatial contexts. Our model was trained on a large dataset of nearly 30 million cells across 18 tissues, allowing Novae to perform zero-shot domain inference across multiple gene panels, tissues, and technologies. Unlike other models, it also natively corrects batch effects and constructs a nested hierarchy of spatial domains. Furthermore, Novae supports various downstream tasks, including spatially variable gene or pathway analysis and spatial domain trajectory analysis. Overall, Novae provides a robust and versatile tool for advancing spatial transcriptomics and its applications in biomedical research.
DNA Damage Response Deficiency Enhances Neuroblastoma Progression and Sensitivity to Combination PARP and ATR Inhibition
Authors: Hayes Madeline N. , Cohen-Gogo Sarah , Kee Lynn , Weiss Alex , Layeghifard Mehdi , Ladumor Yagnesh , Valencia-Sama Ivette , Rajaselvam Anisha , Kaplan David R. , Villani Anita , Shlien Adam , Morgenstern Daniel A. , Irwin Meredith S. 
Published: September 2024

AbstractNext generation sequencing of neuroblastoma (NB) tumors have revealed frequent somatic and germline genetic alterations in genes encoding proteins involved in DNA damage response (DDR) pathways. Despite being well-studied in many adult cancers, roles for DDR disruption in pediatric solid tumors remains poorly understood. To address this, patient-relevant loss-of-function mutations in DDR pathway components including Brca2, Atm, and Palb2 were incorporated into an established zebrafish MYCN transgenic model (Tg(dbh:EGFP-MYCN)). These mutations were found to enhance NB formation and metastasisin vivo, and result in upregulation of proliferation, cell cycle checkpoint and DNA damage repair transcriptional signatures, revealing potential molecular vulnerabilities in DDR-deficient NB. Zebrafish DDR-deficient NB and human NB cells with DDR protein knock-down were sensitive to the poly(ADP-ribose)-polymerase (PARP) inhibitor olaparib, and this effect was further enhanced by inhibition of the ataxia telangiectasia and rad3 related (ATR) kinase. Altogether, our data supports a functional role for DDR-deficiency in NBin vivoand therapeutic potential for combination PARP + ATR inhibition in NB patients with alterations in DDR genes.SignificanceThis work provides the firstin vivoevidence supporting a functional role for DDR-deficiency in NB by demonstrating that alterations in certain DDR pathway genes promote NB formation and metastasis. NGS and pre-clinical drug testing also provides rationale for PARP + ATR inhibitor therapy combinations for patients with NB and pathogenic DDR pathway alterations.
Barcode activity in a recurrent network model of the hippocampus enables efficient memory binding
Authors: Fang Ching , Lindsey Jack , Abbott L.F. , Aronov Dmitriy , Chettih Selmaan 
Published: September 2024

AbstractForming an episodic memory requires binding together disparate elements that co-occur in a single experience. One model of this process is that neurons representing different components of a memory bind to an “index” — a subset of neurons unique to that memory. Evidence for this model has recently been found in chickadees, which use hippocampal memory to store and recall locations of cached food. Chickadee hippocampus produces sparse, high-dimensional patterns (“barcodes”) that uniquely specify each caching event. Unexpectedly, the same neurons that participate in barcodes also exhibit conventional place tuning. It is unknown how barcode activity is generated, and what role it plays in memory formation and retrieval. It is also unclear how a memory index (e.g. barcodes) could function in the same neural population that represents memory content (e.g. place). Here, we design a biologically plausible model that generates barcodes and uses them to bind experiential content. Our model generates barcodes from place inputs through the chaotic dynamics of a recurrent neural network and uses Hebbian plasticity to store barcodes as attractor states. The model matches experimental observations that memory indices (barcodes) and content signals (place tuning) are randomly intermixed in the activity of single neurons. We demonstrate that barcodes reduce memory interference between correlated experiences. We also show that place tuning plays a complementary role to barcodes, enabling flexible, contextually-appropriate memory retrieval. Finally, our model is compatible with previous models of the hippocampus as generating a predictive map. Distinct predictive and indexing functions of the network are achieved via an adjustment of global recurrent gain. Our results suggest how the hippocampus may use barcodes to resolve fundamental tensions between memory specificity (pattern separation) and flexible recall (pattern completion) in general memory systems.