bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continent-wide genomic analysis of the African buffalo (Syncerus caffer)
Authors: Talenti Andrea , Wilkinson Toby , Cook Elizabeth A. , Hemmink Johanneke D. , Paxton Edith , Mutinda Matthew , Ngulu Stephen D. , Jayaraman Siddharth , Bishop Richard P. , Obara Isaiah , Hourlier Thibaut , Giron Carlos Garcia , Martin Fergal J. , Labuschagne Michel , Atimnedi Patrick , Nanteza Anne , Keyyu Julius D. , Mramba Furaha , Caron Alexandre , Cornelis Daniel , Chardonnet Philippe , Fyumagwa Robert , Lembo Tiziana , Auty Harriet K. , Michaux Johan , Smitz Nathalie , Toye Philip , Robert Christelle , Prendergast James G.D. , Morrison Liam J. 
Published: November 2023

AbstractThe African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest qualityde novogenome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.
DONOR VARIABILITY IN HUMAN MESENCHYMAL STEM CELL OSTEOGENIC RESPONSE AS A FUNCTION OF PASSAGE CONDITIONS AND DONOR SEX
Authors: Kolliopoulos Vasiliki , Tiffany Aleczandria , Polanek Maxwell , Harley Brendan A.C. 
Published: November 2023

ABSTRACTContemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their potential to differentiate to various tissue-specific cells and generate a pro-regenerative secretome. While MSC differentiation and therapeutic potential can differ as a function of matrix environment, it may also be widely influenced as a function of donor-to-donor variability. Further, effects of passage number and donor sex may further convolute the identification of clinically effective MSC-mediated regeneration technologies. We report efforts to adapt a well-defined mineralized collagen scaffold platform to study the influence of MSC proliferation and osteogenic potential as a function of passage number and donor sex. Mineralized collagen scaffolds broadly support MSC osteogenic differentiation and regenerative potency in the absence of traditional osteogenic supplements for a wide range of MSCs (rabbit, rat, porcine, human). We obtained a library of bone marrow and adipose tissue derived stem cells to examine donor-variability of regenerative potency in mineralized collagen scaffolds. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex-based differences. Notably, MSCs from male donors displayed significantly higher metabolic activity and proliferation while MSCs from female donor displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. Our study highlights the essentiality of considering MSC donor sex and culture expansion in future studies of biomaterial regenerative potential.
Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth
Authors: Hernández Luis Cruz , Montero María Teresa Sánchez , Rivera-Ramos Alberto , García-Revilla Juan , Talaverón Rocío , Mulero-Acevedo Marta , Venero José Luis , Soto Manuel Sarmiento 
Published: November 2023

ABSTRACTThe glycoprotein Galectin-3 (Gal-3) is a multifunctional molecule that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain’s immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, assume critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.
Theta activity discriminates high-level, species-specific body processes
Authors: Chesley Jane , Riecke Lars , Lu Juanzhi , Vogels Rufin , de Gelder Beatrice 
Published: November 2023

AbstractAmong social stimuli that trigger rapid reactions, body images occupy a prominent place. Given that bodies carry information about other agents’ intentions, actions and emotional expressions, a foundational question concerns the neural basis of body processing. Previous fMRI studies have investigated this but were not yet able to clarify the time course and its functional significance. The present EEG study investigated the role of slow oscillatory cortical activity in body processing and species-specificity. Human participants viewed naturalistic images of human and monkey bodies, faces, and objects, along with mosaic-scrambled versions to control for low-level visual features. Analysis of event-related theta power (4 – 7 Hz) combined with data-driven methods revealed a strong, body-evoked neural response that is specific to human bodies and likely originates from a widespread cortical region during a time window of 150 – 550 ms after the onset of the body image. Our results corroborate recent research proposing a widespread, species-specific cortical network of human body processing. We submit that this network may play an essential role in linking body processes to movement intentions.
Frontal oscillatory beta bursts have rhythmically distinct regimes with differing functional relevance
Authors: Langford Zachary D , Procyk Emmanuel , Wilson Charles R E 
Published: November 2023

AbstractThe importance of studying the transient burst-like nature of beta- and gamma-band oscillations has become increasingly clear. This approach challenges accepted interpretations of oscillatory behavior and emphasizes the importance of examining phenomena at appropriate temporal scales, as opposed to trial averages. Diversity in the detailed temporal form of these real-time phenomena has been under-considered, yet it should provide important information about function. Here we studied such bursts at beta frequencies, and explicitly distinguished transient bursts characterized by high power (BoP) and those marked by consistent cycles (BoC) using methods tailored to capture each characteristic. Analysis of neural recordings from mice and macaques revealed two distinct and largely independent beta burst categories within the same temporal content. BoP bursts were true transients featuring a substantial amplitude peak and minimal rhythmicity, while BoC bursts were much more rhythmic, seemingly meeting a more classic definition of an oscillation. Importantly, these two classes of beta burst showed differing functional relevance within the same signal. In a search-repeat task, BoC bursts occurred more often in the search phase, whereas BoP bursts dominated the repeat phase. As such, beta frequency neural signals encompass at least two transient phenomena, each with potentially distinct functional roles.
Bacterial community characterization by deep learning aided image analysis in soil chips
Authors: Zou Hanbang , Sopasakis Alexandros , Maillard François , Karlsson Erik , Duljas Julia , Silwer Simon , Ohlsson Pelle , Hammer Edith C. 
Published: November 2023

AbstractSoil microbes play an important role in governing global processes such as carbon cycling, but it is challenging to study them embedded in their natural environment and at the single cell level due to the opaque nature of the soil. Nonetheless, progress has been achieved in recent years towards visualizing microbial activities and organo-mineral interaction at the pore scale, especially thanks to the development of microfluidic ‘soil chips’ creating transparent soil model habitats. Image-based analyses come with new challenges as manual counting of bacteria in thousands of digital images taken from the soil chips is excessively time-consuming, while simple thresholding cannot be applied due to the background of soil minerals and debris. Here, we adopt the well-developed deep learning algorithm Mask-RCNN to quantitatively analyse the bacterial communities in soil samples from different locations in the world. This work demonstrates analysis of bacterial abundance from three contrasting locations (Greenland, Sweden and Kenya) using deep learning in microfluidic soil chips in order to characterize population and community dynamics. We additionally quantified cell- and colony morphology including cell size, shape and the cell aggregation level via calculation of the distance to the nearest neighbor. This approach allows for the first time an automated visual investigation of soil bacterial communities, and a crude biodiversity measure based on phenotypic cell morphology, which could become a valuable complement to molecular studies.
Age-Related Differences in Affective Behaviors in Mice: Possible Role of Prefrontal Cortical-Hippocampal Functional Connectivity and Metabolomic Profiles
Authors: Febo Marcelo , Mahar Rohit , Rodriguez Nicholas A. , Buraima Joy , Pompilus Marjory , Pinto Aeja M. , Grudny Matteo M. , Bruijnzeel Adriaan W. , Merritt Matthew E. 
Published: November 2023

AbstractThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation. We assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics. Our results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and with re-testing with a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups. The results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.
Darwin’s “neuters” and the evolution of the sex continuum in a superorganism
Authors: Oettler J , Wallner T , Dofka B , Heinze J , Eichner N , Meister G , Errbii M , Rehli M , Gebhard C , Schultner E 
Published: November 2023

AbstractAnt castes are an amazing example of phenotypic plasticity. In worker-destined embryos of the antCardiocondyla obscurior, the default female developmental trajectory is interrupted even before the gonadal precursor cells acquire a sexual identity. miRNA and mRNA expression in embryos reveal three distinct phenotypic entities: males, females, and “neuters”, as Darwin coined the worker caste in “On the Origin of Species”. Based on these results we propose that haplodiploidy, in conjunction with insect sex determination, allows for the expression of a third dimension on the sex continuum, thus facilitating the evolution of individuals which develop traits their parents do not have.One sentence summarySex and caste differentiation begin during the same embryonic developmental window in the antCardiocondyla obscurior.
GAUSS-EM: Guided accumulation of ultrathin serial sections with a static magnetic field for volume electron microscopy
Authors: Fulton Kara A , Watkins Paul V , Briggman Kevin L 
Published: November 2023

AbstractSerial sectioning electron microscopy of millimeter-scale 3D anatomical volumes requires the collection of thousands of ultrathin sections. Here we report a high-throughput automated approach, GAUSS-EM, utilizing a static magnetic field to collect and densely pack thousands of sections onto individual silicon wafers. The method is capable of sectioning hundreds of microns of tissue per day at section thicknesses down to 35 nm. Relative to other automated volume electron microscopy approaches, GAUSS-EM democratizes the ability to collect large 3D EM volumes because it is simple and inexpensive to implement. We present two exemplar EM volumes of a zebrafish eye and mouse olfactory bulb collected with the method.
UNSEG: unsupervised segmentation of cells and their nuclei in complex tissue samples
Authors: Kochetov Bogdan , Bell Phoenix , Garcia Paulo S. , Shalaby Akram S. , Raphael Rebecca , Raymond Benjamin , Leibowitz Brian J. , Schoedel Karen , Brand Rhonda M. , Brand Randall E. , Yu Jian , Zhang Lin , Diergaarde Brenda , Schoen Robert E. , Singhi Aatur , Uttam Shikhar 
Published: November 2023

ABSTRACTMultiplexed imaging technologies have made it possible to interrogate complex tumor microenvironments at sub-cellular resolution within their native spatial context. However, proper quantification of this complexity requires the ability to easily and accurately segment cells into their sub-cellular compartments. Within the supervised learning paradigm, deep learning based segmentation methods demonstrating human level performance have emerged. However, limited work has been done in developing such generalist methods within the label-free unsupervised context. Here we present an unsupervised segmentation (UNSEG) method that achieves deep learning level performance without requiring any training data. UNSEG leverages a Bayesian-like framework and the specificity of nucleus and cell membrane markers to construct ana posterioriprobability estimate of each pixel belonging to the nucleus, cell membrane, or background. It uses this estimate to segment each cell into its nuclear and cell-membrane compartments. We show that UNSEG is more internally consistent and better at generalizing to the complexity of tissue morphology than current deep learning methods. This allows UNSEG to unambiguously identify the cytoplasmic compartment of a cell, which we employ to demonstrate its use in an exemplar biological scenario. Within the UNSEG framework, we also introduce a new perturbed watershed algorithm capable of stably and automatically segmenting a cluster of cell nuclei into individual cell nuclei that increases the accuracy of classical watershed. Perturbed watershed can also be used as a standalone algorithm that researchers can incorporate within their supervised or unsupervised learning approaches to extend classical watershed, particularly in the multiplexed imaging context. Finally, as part of developing UNSEG, we have generated a high-quality annotated gastrointestinal tissue (GIT) dataset, which we anticipate will be useful for the broader research community. We demonstrate the efficacy of UNSEG on the GIT dataset, publicly available datasets, and on a range of practical scenarios. In these contexts, we also discuss the possibility of bias inherent in quantification of segmentation accuracy based onF1score. Segmentation, despite its long antecedents, remains a challenging problem, particularly in the context of tissue samples. UNSEG, an easy-to-use algorithm, provides an unsupervised approach to overcome this bottleneck, and as we discuss, can help improve deep learning based segmentation methods by providing a bridge between unsupervised and supervised learning paradigms.
Gait speed is a biomarker of cancer-associated cachexia decline and recovery
Authors: Roy Ishan , Binder-Markey Ben , Sychowski Danielle , Willbanks Amber , Phipps Tenisha , McAllister Donna , Bhakta Akash , Marquez Emily , D’Andrea Dominic , Franz Colin , Pichika Rajeswari , Dwinell Michael B. , Jayabalan Prakash , Lieber Richard L. 
Published: November 2023

AbstractBackgroundProgressive functional decline is a key element of cancer-associated cachexia. No therapies have successfully translated to the clinic due to an inability to measure and improve physical function in cachectic patients. Major barriers to translating pre-clinical therapies to the clinic include lack of cancer models that accurately mimic functional decline and use of non-specific outcome measures of function, like grip strength. New approaches are needed to investigate cachexia-related function at both the basic and clinical science levels.MethodsSurvival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were then assessed for muscle wasting, inflammation, and functional decline using a battery of biochemical, physiologic, and behavioral techniques. In parallel, we analyzed a 156-subject cohort of cancer patients with a range of cachexia severity, and who required rehabilitation, to determine the relationship between gait speed via six-minute walk test (6MWT), grip strength (hGS), and functional independence measures (FIM). Cachectic patients were identified using the Weight Loss Grading Scale (WLGS), Fearon consensus criteria, and the Prognostic Nutritional Index (PNI).ResultsUsing a 100-cell dose of DT10022 KPC cells, we extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation compared to higher doses used (p<0.001). In this Low-dose Orthotopic (LO) model, both progressive skeletal and cardiac muscle wasting were detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2 week post-implantation whereas grip strength change was a late event and related to end of life. Principle component analysis (PCA) revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). These data paralleled our observations in cancer patients with cachexia who required rehabilitation. In cachectic patients (identified by WLGS, Fearon criteria, or PNI, change in 6MWT correlated with motor FIM score changes while hGS did not (r2=0.18, p<0.001). This relationship between 6MWT and FIM in cachectic patients was further confirmed through multivariate regression (r2=0.30, p<0.001) controlling for age and cancer burden.ConclusionOutcome measures linked to gait are better associated with cachexia related function and preferred for future pre-clinical and clinical cachexia studies.
Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity
Authors: Appios Anna , Davies James , Sirvent Sofia , Henderson Stephen , Trzebanski Sébastien , Schroth Johannes , Law Morven L. , Boal Carvalho Inês , Yuan-Hao Kan Howard , Lovlekar Shreya , Major Christina , Vallejo Andres , Hall Nigel J. , Ardern-Jones Michael , Henson Sian M. , Emmerson Elaine , Jung Steffen , Polak Marta E. , Bennett Clare L. 
Published: November 2023

AbstractLangerhans cells (LCs) maintain tissue and immunological homeostasis at the epidermal barrier site. They are unique among phagocytes in functioning both as embryo-derived, tissue-resident macrophages that influence skin innervation and repair, and as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DCs). Here we report the mechanisms that determine this dual identity. Using ablation of embryo-derived LCs in murine adult skin and tracked differentiation of incoming monocyte-derived replacements, we reveal intrinsic intra-epidermal heterogeneity. We demonstrate that monocyte-dendritic cell progenitor (MDP)-derived monocytes are selected for survival in the skin environment. Within the epidermis, the hair follicle niche subsequently provides an initial site of LC commitment, likely via Notch signaling, prior to metabolic adaptation and survival of differentiated monocyte-derived LCs. In human skin, we show that embryo-derived (e)LCs in newborns retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after post-natal expansion of eLCs. Thus, intrinsic and extrinsic adaptations to adult skin niches replicate conditioning of eLC at birth, permitting repair of the unique LC network.
Manual gestures facilitate learning lexical stress by modulating auditory neural responses
Authors: Zhan Tianqi , Yang Danfeng , Wu Ruoyu , Tian Xing 
Published: November 2023

AbstractGestures accompany speech and facilitate communication and learning. Most previous studies have demonstrated the effects of gestures on learning semantics, yet how gestures facilitate learning low- and intermediate-level speech features is unclear. The present study investigated the effects of manual gestures on learning lexical stress, a phonological-lexical feature that is foreign to native Mandarin speakers. Across a series of experiments, we demonstrated that the gestures with representational relations to auditory stimuli in terms of covaried amplitude modulation facilitated the learning of lexical stress for both familiar (English) and unknown (Russian) languages, but not for pseudowords that lack phonotactic properties. Interestingly, gestures with amplitude trajectory matching the stress benefited the learning of trained words, whereas gestures that only matched the timing of syllable segments but not amplitude variation generalized the learning effects to untrained stimuli. Furthermore, in the EEG experiment, we found that gesture-accompanied learning was associated with power increase and inter-trial phase coherence (ITC) decrease in the theta band at the time windows corresponding to the stress positions. These results suggest that the facilitatory effects of gestures on lexical stress learning depend on the specificity of cross-modal feature mapping at the phonological level, mediated by the neural modulation in early perceptual responses.