bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products
Authors: Castenmiller Suzanne M. , Kanagasabesan Nandhini , Guislain Aurélie , Nicolet Benoît P. , van Loenen Marleen M. , Monkhorst Kim , Veenhof Alexander A.F.A. , Smit Egbert F. , Hartemink Koen J. , Haanen John B.A.G. , de Groot Rosa , Wolkers Monika C. 
Published: February 2024

AbstractAdoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has shown great potential for the treatment of solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy, and the parameters that define the likelihood of TIL products to be tumor reactive are to date unknown. Defining prognostic markers that correlate with high level of tumor-reactivity is key for achieving better tailored immunotherapies.To determine whether the composition of immune cell infiltrates correlates with the tumor-reactivity of expanded TIL products, we employed multi-parameter flow cytometry to characterize the immune cell infiltrates from 26 early-stage, and 20 late-stage NSCLC tumor lesions. Unbiased flow cytometry analysis with Cytotree and Spearman’s Rank Correlation was used to correlate immune infiltrates with the expansion rate, immune cell activation and T cell differentiation state, and the anti-tumor response of TIL products generated from the same lesions.The composition of tumor immune infiltrates was highly variable between patients, irrespective of the disease stage. High percentages of B cell infiltrates positively correlated with the presence of conventional CD4+T cells, and an overall increase of naïve T cell infiltrates. In contrast, high B cell infiltrates negatively correlated with the tumor-reactivity of expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. Tumors with high B cell infiltrates contained IgD+BCL6+B cells and CXCR5+BLC6+CD4+T cell infiltrates and an increased percentage of naïve CD8+T cells, indicative of the presence of tertiary lymphoid structures (TLS) in tumors with high B cell infiltrates.This study reveals that the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of expanded TIL products from NSCLC tumor lesions. Importantly, the tumor-responsiveness of TIL products negatively correlated with the presence of TLS-associated immune infiltrates in tumors. Our finding may thus help improve patient selection for TIL therapy.
Environmental factors and host sex influence the skin microbiome structure of Hong Kong newt (Paramesotriton hongkongensis) in a coldspot of chytridiomycosis in subtropical East Asia
Authors: Wan Bowen , Chen Guoling , Poon Emily Shui Kei , Fung Hon Shing , Lau Anthony , Sin Simon Yung Wa 
Published: February 2024

AbstractChytridiomycosis, an infectious skin disease caused by the chytrid fungi,Batrachochytrium dendrobatidisandB. salamandrivorans, has been threatening global amphibian biodiversity. On the skin of chytrid-resistant amphibians, some antifungal bacteria likely defend them against chytridiomycosis, reducing the mortality of resistant amphibians. The Hong Kong newt (Paramesotriton hongkongensis) inhabits East Asia which is a suspected origin of chytrids. Asymptomatic infection in the newts suggests their long-term coexistence with chytrids. Thus, the skin microbiomes of this resistant species warrant investigation, along with other factors that can affect the microbiome. Among the 149 newts sampled in their natural habitats in Hong Kong, putative antifungal bacteria were found on all newts. There were 314 amplicon sequence variants distributed over 25 genera of putative antifungal bacteria, abundant ones includedAcinetobacter,Flavobacterium, andNovosphingobiumspp. The skin microbiome compositions were strongly influenced by the inter-site geographical distances. Despite inter-site differences, we identified some core skin microbes across sites, which could be vital toP. hongkongensis. The dominant cores included family Comamonadaceae, family Chitinophagaceae, and class Betaproteobacteria. Moreover, habitat elevation and host sex also exhibited significant effects on skin microbiome compositions. The antifungal bacteria found on these newts offer an important resource for conservation against chytridiomycosis, such as probiotic treatments for susceptible species.
Genetic barcodes for ash (Fraxinus) species and generation of new wide hybrids
Authors: Plumb William J. , Kelly Laura J. , Mullender Joe , Powell Robyn F. , Csiba Laszlo , Nemesio-Gorriz Miguel , Carey David , Mason Mary E. , Crowther William , Koch Jennifer , Douglas Gerry C. , Buggs Richard J. A. 
Published: February 2024

AbstractNative ash tree species in Europe and North America are being devastated by ash dieback and the emerald ash borer, respectively. As worldwide ash species differ in their level of susceptibility to these threats, hybrid breeding may allow resistance to be transferred among species. However, we do not know the extent to which distantly related ash species can be crossed, and many ash species are difficult to identify from morphology alone leading to some mislabelling in living collections. Here, we develop a genetic barcode system for the identification ofFraxinusspecies based on three low-copy-number protein coding genes. We also conduct experimental crosses among ash species in different sections.Our barcodes are effective in identifying ash samples to sectional level and in some cases to species level, and can also identify hybrids. They highlight thatF. mandshurica, F. platypodaandF. chiisanensismay be frequently mistaken for one another in living collections. We succeeded in generating ten wide hybrid plants: two of sectionMelioides(species:F. pennsylvanica) □ sectionFraxinus(species:F. excelsior) and eight of sectionOrnus(species unclear) □ sectionFraxinus(species:F. excelsior). One hybrid from each of our crosses has survived natural infection with the ash dieback pathogen in Ireland. We also discovered a hybrid between sectionMelioides(species:F. latifolia) □ sectionFraxinus(species:F. excelsior) formed spontaneously in the ash collection at Kew. Our findings facilitate the deployment of global ash species diversity in response to alien pests and pathogens.Societal impact statementThe world-wide diversity of ash trees includes genetic information encoding resistance to the ash dieback fungus and the emerald ash borer beetle, which are currently devastating ash populations in Europe and North America. In order to mobilise this genetic diversity in conventional breeding programmes we need to be able to accurately identify ash species from around the world, and cross them with one another. Here, we present a genetic barcoding system for ash species, and a series of hybridisation experiments between European ash and other species. Two of the hybrids show early promise against ash dieback.
Evidence of sensory error threshold in triggering locomotor adaptations in humans
Authors: Herrick E. , Yakovenko S. 
Published: February 2024

ABSTRACTChanging body biomechanics or external conditions trigger neural adaptations to optimize motor behavior. While the adaptations appear continuous to minimize movement errors, not all errors necessarily initiate sensorimotor adaptations. The locomotor system exhibits resilience to change and rehabilitation. This suggests the presence of an error threshold to trigger the adaptation mechanism. Here, we imposed kinematic and kinetic constraints of stepping using a passive orthosis and real-time feedback about limb loading. We aimed to manipulate stepping asymmetry and explore the interplay between adaptation and locomotor error magnitude. Uninjured healthy adults were tested in three locomotor conditions: unconstrained, constrained, and washout unconstrained walking. Surprisingly, kinematic asymmetry alone did not induce persistent adaptation. However, the addition of asymmetric interlimb loading triggered the expected adaptation. Our finding suggests that uninjured locomotor systems can cope with a specific range of kinematic asymmetries without initiating persistent adaptations that lead to aftereffects, and that loading may be a key variable for evoking the adaptation. The presence of an error threshold may mitigate possible disruption of vital motor functions and contribute to locomotor adaptation during walking. These insights elucidate the mechanism of neural plasticity and have implications for rehabilitation.
Multiparameter Quantitative Analyses of Diagnostic Cells in Brain Tissues from Tuberous Sclerosis Complex
Authors: Arceneaux Jerome S. , Brockman Asa A. , Khurana Rohit , Chalkley Mary-Bronwen L. , Geben Laura C. , Vestal Matthew , Zafar Muhammad , Weatherspoon Sarah , Mobley Bret C. , Ess Kevin C. , Ihrie Rebecca A. 
Published: February 2024

AbstractThe advent of high-dimensional imaging approaches offers innovative opportunities to molecularly characterize diagnostic cells in disorders that have previously relied on histopathological definitions. One example of such disorders is tuberous sclerosis complex (TSC), a developmental disorder characterized by systemic growth of benign tumors. Within resected brain tissues from patients with TSC, detection of abnormally enlarged balloon cells (BCs) is pathognomonic for this disorder. Though BCs can be identified by an expert neuropathologist, little is known about the specificity and broad applicability of protein markers for these cells, complicating classification of proposed BCs identified in experimental models of this disorder. Here, we report the development of a customized machine-learning workflow (BalloonIdentifier; BAIDEN) that was trained to prospectively identify BCs in tissue sections using a histological stain compatible with high-dimensional cytometry. This approach was coupled to a custom antibody panel and 36-parameter imaging mass cytometry (IMC) to explore the expression of multiple previously proposed BC markers and develop a descriptor of BC features conserved across multiple tissue samples from patients with TSC. These findings comprise a toolbox and dataset for understanding the abundance, structure, and signaling activity of these histopathologically abnormal cells, and an example case of how such tools can be developed and applied within human tissues.
Gene expression signatures of response to fluoxetine treatment: systematic review and meta-analyses
Authors: Cooper David G. , Cowden J. Paige , Stanley Parker A. , Karbowski Jack T. , Gaertig Victoria S. , Lukan Caiden J. , Vo Patrick M. , Worthington Ariel D. , Class Caleb A. 
Published: February 2024

ABSTRACTBackgroundSelecting the best antidepressant for a patient with major depressive disorder (MDD) remains a challenge, and some have turned to genomic (and other ‘omic) data to identify an optimal therapy. In this work, we synthesized gene expression data for fluoxetine treatment in both human patients and rodent models, to better understand biological pathways affected by treatment, as well as those that may distinguish clinical or behavioral response.MethodsFollowing the PRISMA guidelines, we searched the Gene Expression Omnibus (GEO) for studies profiling humans or rodent models with treatment of the antidepressant fluoxetine, excluding those not done in the context of depression or anxiety, in an irrelevant tissue type, or with fewer than three samples per group. Included studies were systematically reanalyzed by differential expression analysis and Gene Set Enrichment Analysis (GSEA). Individual pathway and gene statistics were synthesized across studies by three p-value combination methods, and then corrected for false discovery.ResultsOf the 74 data sets that were screened, 20 were included: 18 in rodents, and two in tissue from human patients. Studies were highly heterogeneous in the comparisons of both treated vs. control samples and responders vs. non-responders, with 737 and 356 pathways, respectively, identified as significantly different between groups in at least one study. However, 19 pathways were identified as consistently different in responders vs. non-responders, including toll-like receptor (TLR) and other immune pathways. Signal transduction pathways were identified as consistently affected by fluoxetine treatment in depressed patients and rodent models.DiscussionThese meta-analyses confirm known pathways and provide new hints toward antidepressant resistance, but more work is needed. Most included studies involved rodent models, and both patient studies had small cohorts. Additional large-cohort studies applying additional ‘omics technologies are necessary to understand the intricacies and heterogeneity of antidepressant response.
The sperm hook in house mice: a functional adaptation for migration and self-organised behaviour
Authors: Ryu Heungjin , Nam Kibum , Lee Byeong Eun , Jeong Yundon , Lee Seunghun , Kim Jeongmo , Hyun Young-Min , Kim Jae-Ick , Park Jung-Hoon 
Published: February 2024

AbstractIn most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract inMus musculus(C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronised sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.
Sniffing can be initiated by dopamine’s actions on ventral striatum neurons
Authors: Johnson Natalie L. , Cotelo-Larrea Anamaria , Stetzik Lucas A. , Akkaya Umit M. , Zhang Zihao , Gadziola Marie A. , Varga Adrienn G. , Ma Minghong , Wesson Daniel W. 
Published: February 2024

AbstractSniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The neuromodulatory systems which influence the display of sniffing are unclear. Here, we report that dopamine release into the ventral striatum is coupled with bouts of sniffing and that stimulation of dopaminergic terminals in these regions drives increases in respiratory rate to initiate sniffing whereas inhibition of these terminals reduces respiratory rate. Both the firing of individual neurons and the activity of post-synaptic D1 and D2 receptor-expressing neurons in the ventral striatum are also coupled with sniffing and local antagonism of D1 and D2 receptors squelches sniffing. Together, these results support a model whereby sniffing can be initiated by dopamine’s actions upon ventral striatum neurons. The nature of sniffing being integral to both olfaction and motivated behaviors implicates this circuit in a wide array of functions.
Altered NRG1/ErbB4 signaling and cholesterol metabolism dysregulation are key pathomechanisms in VRK1-related motor neuropathies and motor neuron diseases
Authors: Hamzé Zeinab , Humbert Camille , Rihan Khalil , Roeckel-Trévisiol Nathalie , Castro Christel , Lenfant Nicolas , Aubert Catherine , Bertaux Karine , Jabbour Rosette , Bernard-Marissal Nathalie , Mégarbané André , Delague Valérie 
Published: February 2024

AbstractHereditary Motor and Sensory Neuropathy (HMSN), or Charcot-Marie-Tooth disease (CMT), are the most common group of Inherited peripheral neuropathies (IPN), characterized by a strong clinical and genetic heterogeneity. Among them, distal Hereditary Motor Neuropathy (dHMN), also known as neuronopathy, is a subgroup, where only motor nerves are affected. This subgroup is also genetically heterogeneous, with 25 genes described to date, of which VRK1, that we have recently described as responsible for dHMN, associated to upper motor neuron signs. There are now more than thirty mutations in VRK1, which cause a range of neurological diseases affecting motor neurons (mainly lower, but also upper) or their axons in the peripheral nervous system, that we design as VRK1-related motor neuron diseases.In two previous studies, we have demonstrated that dHMN due to VRK1 mutations lead to reduced levels of VRK1 in the nucleus, and that this depletion alters the dynamics of coilin, a phosphorylation target of VRK1. hiPSC-derived Motor Neurons (hiPSC-MN) from these patients, display Cajal Bodies (CBs) disassembly and defects in neurite outgrowth and branching, altered Action Potential (AP) waveform and decreased Axonal Initial Segment (AIS) length.In this study, we have further studied the link between the loss of VRK1 function and the defects observed in hiPSC-MNs, by realizing bulk mRNA-Seq sequencing in this in vitro model of the disease. Our results evidenced altered NRG1/ERBB4 signaling, leading to cholesterol metabolism dysregulation and deregulation of genes encoding the glutamate receptors AMPAR and NMDAR, which role in the Axonal Initial Segment and abnormal AP initiation in hiPSC-MNs remains to be investigated.
Pathogenic tau induces an adaptive elevation in mRNA translation rate at early stages of disease
Authors: Zuniga Gabrielle , Katsumura Sakie , Mange Jasmine De , Ramirez Paulino , Atrian Farzaneh , Morita Masahiro , Frost Bess 
Published: February 2024

ABSTRACTAlterations in the rate and accuracy of messenger RNA (mRNA) translation are associated with aging and several neurodegenerative disorders, including Alzheimer’s disease and related tauopathies. We previously reported that error-containing RNA that are normally cleared via nonsense-mediated mRNA decay (NMD), a key RNA surveillance mechanism, are translated in the adult brain of aDrosophilamodel of tauopathy. In the current study, we find that newly-synthesized peptides and translation machinery accumulate within nuclear envelope invaginations that occur as a consequence of tau pathology, and that the rate of mRNA translation is globally elevated in early stages of disease in adult brains ofDrosophilamodels of tauopathy. Polysome profiling from adult heads of tau transgenicDrosophilareveals the preferential translation of specific mRNA that have been previously linked to neurodegeneration. Unexpectedly, we find that panneuronal elevation of NMD further elevates the global translation rate in tau transgenicDrosophila, as does treatment with rapamycin. As NMD activation and rapamycin both suppress tau-induced neurodegeneration, their shared effect on translation suggests that elevated rates of mRNA translation are an early adaptive mechanism to limit neurodegeneration. Our work provides compelling evidence that tau-induced deficits in NMD reshape the tau translatome by increasing translation of RNA that are normally repressed in healthy cells.
The genomic and cultural diversity of the Inka Qhapaq hucha ceremony in Chile and Argentina
Authors: de la Fuente Castro Constanza , Cortés Constanza , Raghavan Maanasa , Castillo Daniela , Castro Mario , Verdugo Ricardo , Moraga Mauricio 
Published: February 2024

AbstractThe South American archaeological record has ample evidence of the socio-cultural dynamism of human populations in the past. This has also been supported through the analysis of ancient genomes, by showing evidence of gene flow across the region. While the extent of these signals is yet to be tested, the growing number of ancient genomes allows for more fine-scaled hypotheses to be evaluated. In this study, we assessed the genetic diversity of individuals associated with the Inka ritual, Qhapaq hucha. As part of this ceremony, one or more individuals were buried with Inka and local-style offerings on mountain summits along the Andes, leaving a very distinctive record. Using paleogenomic tools, we analyzed three individuals: two newly-generated genomes from El Plomo Mountain (Chile) and El Toro Mountain (Argentina), and a previously published genome from Argentina (Aconcagua Mountain). Our results reveal a complex demographic scenario with each of the individuals showing different genetic affinities. Furthermore, while two individuals showed genetic similarities with present-day and ancient populations from the southern region of the Inka empire, the third individual may have undertaken long-distance movement. The genetic diversity we observed between individuals from similar cultural contexts supports the highly diverse strategies the Inka implemented while incorporating new territories. More broadly, this research contributes to our growing understanding of the population dynamics in the Andes by discussing the implications and temporality of population movements in the region.
Retention of the full visual opsin repertoire in Australia’s cryptozoic lizards
Authors: Ford Matthew J.R. , Ludington Alastair J. , Bradford Tessa , Sanders Kate L. , Hutchinson Mark N. , Simões Bruno F. 
Published: February 2024

AbstractAustralian scincid lizards in the sister-generaLeristaandCtenotusare a prominent system for understanding adaptation in the transition from surface to fossorial life. The approximately 205 species in this group exhibit extreme diversity in morphology and ecology.LeristaandCtenotusboth include diurnal and surface-active species that are fully pentadactyl, andLeristaalso contains many specialised limb-reduced and limbless sand-swimmers. To understand how the visual systems of these lizards have responded to their varied photic environments, we examined the five opsin genes encoding the pigments that mediate colour and dim-light vision. These genes were sequenced for 59 species ofLeristaandCtenotusand analysed for variation in selection pressures among amino acid sites and across branches in the species tree. All five opsins are present and intact in all species ofLeristaandCtenotusexamined, and we identified signals of positively selected substitutions in all five opsin genes –RH1, which mediates scotopic vision, and four cone opsins associated with photopic vision (SWS1, SWS2, RH2, LWS). Most comparisons of selection pressures did not show significant differences according to broad ecological divisions. Only LWS showed a signal of relaxed selection in sand-swimming (limb reduced) versus less fossorial (fully limbed)Lerista. These results suggest that photopic abilities are retained across both clades, even in the most fossorial species, highlighting a need for studies of visual ecology of Australian skinks, and prompts caution with regards to generalisations about degenerate vision in fossorial squamates.