bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of Cellular Senescence in Ciliates
Authors: Mitteldorf Josh 
Published: September 2024

AbstractMixing and sharing of genes is essential for population diversity, which contributes to the resilience and, ultimately, the survival of animal and plant communities. However, sharing of genes is antithetical to individual fitness; hence gene mixing is threatened with extinction if selection rewards selfish (clonal) reproduction. To address this dilemma, mechanisms have evolved to enforce a mandate for gene sharing. In most metazoa, the functions of sex and reproduction are tightly entwined, presumably for the purpose of compelling the sharing of genes. In protists, the functions of sex (conjugation) and reproduction (amitosis) are separate. The mandate for gene sharing is enforced, instead, by a form of cellular senescence. Ciliates can reproduce clonally a few hundred times before they senesce and die. Conjugation resets their biological clock, restarting the cycle of clonal reproduction. The question how reproduction in metazoa came to be linked to sex has been explored in the past, but a fully satisfying account in terms of evolutionary ecology is lacking. The question how senescence in protozoa came to be linked to sex has not been addressed, and is the topic of the current study. I present herein two numerical simulations (IBMs) for the evolution of cellular senescence in ciliates. The results shed light not only on the evolution of senescence in higher life forms, but on more general questions concerning the plausibility of group selection.
The coevolution of encephalization and manual dexterity in hominins and other primates
Authors: Baker Joanna , Barton Robert A. , Venditti Chris 
Published: September 2024

AbstractThe human hand is one of our most remarkable features. We have long, opposable thumbs and a suite of other features argued to be adaptations for interacting with and manipulating our environment, literally extending the reach of our cognitive powers. Consequently, enhanced manipulative dexterity, tool use and increased brain size are considered key features of how our ancestors evolved. This hypothesis predicts that anatomical dexterity and brain size co-evolved, and that this should be evident in the morphology of the hand. To test this hypothesis and to understand how hominin evolution may have deviated from any general primate trend, we collected a dataset of finger length, thumb length, and brain size across 94 extinct and extant species of primates. Using phylogenetic comparative methods, we reveal a strong primate-wide association between brain size and relative thumb length. We further demonstrate that this general association accurately predicts the co-evolution of these traits in hominins. Whilst hominins have significantly long thumbs compared to other primates, we infer that they have arisen from the same underlying evolutionary process acting across the whole primate order: increasing manipulative ability associated with specialized neural control processes. The relationships we recover are consistent with positive feedback between manipulation, tool use and cognition and therefore may go some way towards explaining evolutionary trends towards larger brain sizes among primates, and particularly in hominins. Our results emphasize the role of manipulative abilities in cognitive evolution and emphasize how neural and bodily adaptations are interconnected.
The MAASWERP study: An international, comparative case study on measuring biomechanics of the aged murine aorta
Authors: Neutel Cédric H.G. , van der Laan Koen W.F. , Wesley Callan D. , Krüger Dustin N. , Pencheva Margarita G. , Schalkwijk Casper G. , De Meyer Guido R.Y. , Martinet Wim , Delhaas Tammo , Reesink Koen D. , Giudici Alessandro , Guns Pieter-Jan , Spronck Bart 
Published: September 2024

AbstractArterial stiffening is a hallmark of vascular ageing, and unravelling its underlying mechanisms has become a central theme in the field of cardiovascular disease. While various techniques and experimental setups are accessible for investigating biomechanics of blood vessels bothin vivoandex vivo, comparing findings across diverse methodologies is challenging. In the present study, we aimed to compare arterial stiffness measurements of two distinctex vivosetups for measuring aortic mechanics. First, we measured arterial stiffness in the aorta of adult (5 months) and aged (24 months) wild-type C57Bl/6J micein vivo, after whichex vivobiomechanical evaluation was performed using the Rodent Oscillatory Tension Setup to study Arterial Compliance (ROTSAC; University of Antwerp, Belgium) and the DynamX setup (Maastricht University, The Netherlands). Measurements in both setups were conducted in parallel with matched protocols and identical buffers and chemicals. Overall, both methods revealed age-related increased stiffness, although parameters of aortic mechanics showed different numerical values, suggesting that results are not directly interchangeable between methods. Surprisingly, smooth muscle cell contraction had opposing effects between the setups. Indeed, smooth muscle cell contraction increased arterial stiffness in the ROTSAC but decreased stiffness in the DynamX. These opposing effects could be attributed to how the two setups differentially load the collagen fibres in the arterial wall,ex vivo. In conclusion, the observed differences between the twoex vivosetups highlight the necessity to report findings on (altered) aortic mechanics in the context of the used methodology.
Physiologically based demographic model/GIS analyses of thirteen invasive species in Africa: why the biology matters
Authors: Gutierrez Andrew Paul , Ponti Luigi , Neteler Markus , Cure Jose Ricardo , Kenmore Peter E. , Simmons George 
Published: September 2024

AbstractGlobally, research and policy groups often lack the expertise to develop appropriate models to analyze agroecological and invasive species problems holistically to inform management and quarantine policy development under extant and climate change over wide geographic landscapes. Off-the-shelf species distribution models (SDM) correlate weather and other variables to records of species presence and have become the mainstay for predicting the geographic distribution and favorability of invasive species (Elith 2017). However, SDM analyses lack the capacity to examine the underpinning dynamics of agroecosystems required to inform policy and develop management strategies. We propose that age-structured physiologically based demographic models (PBDMs) can solve important aspects of this challenge as they can be used to examine prospectively species dynamics locally as well as their potential geographic distribution and relative abundance across vast areas independent of presence records. PBDMs fall under the ambit of time-varying life tables (TVLTs; cf. Gilbertet al. 1976) and capture the weather driven biology, dynamics, and interactions of species, and can be used to examine the system from the perspective of any of the interacting species. Here, we use the PBDM structure to examine the dynamics across Africa of thirteen invasive species from various taxa having diverse biology and trophic interactions (see Gutierrez 1996, Gutierrez and Ponti 2013a). PBDMs are perceived to be difficult to develop, hence theraison d’êtreis to show this is not the case and illustrate their utility invasive and endemic agricultural and medical/veterinary pest species at the local and the large geographic scale of Africa. We note that PBDMs provide a structure for continued model improvements.The development of open access software is proposed to facilitate PBDM development by non-experts emphasizing the crucial role of sound biological data on species responses to weather and to other species in a multi-trophic, interactions, and provide a guide for collecting the appropriate biological data. While the emphasis is on plant/arthropod interactions, models of diseases can be accommodated. The Supplemental Materials summarizes a large array of heritage PBDMs reported in the literature based on the methods outline herein, noting that the same model structure can be used to analyze and manage non pest species.
DIFFERENTIAL ANTIPROLIFERATIVE EFFECTS OF CANNABIDIOL (CBD) IN THE CORE AND INFILTRATIVE BOUNDARY OF HUMAN GLIOBLASTOMA CELLS
Authors: Abassi-Rana Ghazala , Calle-Patino Yolanda , Molina-Holgado Francisco 
Published: September 2024

AbstractBackgroundWe have previously reported that the brain cannabinoid signalling pathways regulates in the isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core and infiltrative boundary tumor cell proliferation. To uncover the mechanism behind these effects we have investigated the possible antitumoral actions of cannabidiol (CBD) in the tumour core cells (U87) and the Glioma Invasive Margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease.MethodsMonolayer of GBM cells cultures were treated with increasing concentrations of CBD, Temozolomide (TMZ), Carmustine (BCUN), Fluoxetine, Doxorubicine (DOX) or vehicle. After treatment, cell viability was assessed using an MTT kit assay to evaluate mitochondrial activity/cell proliferation, cytotoxicity was evaluated by LDH release. In addition, we have investigated the effects of the CBD alone or in combination with the above drugs on the autophagic cell death, unfold protein response (UPR) mitochondrial response and release of proinflammatory cytokines.SummaryThis study highlights the potential therapeutic relevance of CBD in combination with other FDA-approved drugs against glioblastoma. We observed strong synergism between CBD and TMZ, FX, and DOXO in reducing U87-MG cell viability in vitro, with even stronger synergy between CBD and TMZ in GIN-8 cells. Our preliminary data identify CBD as a potential anti-neoplastic drug in both core and invasive margin cells. Given the heterogeneity of glioblastoma, further studies will elucidate the molecular mechanisms underlying CBD observed anti-tumoral actions and determine whether it can potentially be used in the future as an addition to current therapies.
CDK4 inactivation balances resistance to apoptosis with heightened metabolic sensitivity in triple negative breast cancer cells
Authors: Ziegler Dorian V. , Leal-Esteban Lucia , Parashar Kanishka , Castro Wilson , Zanou Nadège , Huber Katharina , López-Alcalá Jaime , Berney Xavier Pascal , Malagón María M , Roger Catherine , Berger Marie-Agnès , Paone Giulia , Gallart-Ayala Hector , Ivanisevic Julijana , Rieusset Jennifer , Irving Melita , Fajas Lluis 
Published: September 2024

SummaryThe shift in the energetic demands of proliferating cells during tumorigenesis requires intense crosstalk between the cell cycle and metabolism. Beyond their role in cell proliferation, cell cycle regulators also modulate intracellular metabolism in normal tissues. However, in the context of cancer, where CDK4 is upregulated or stabilized, the metabolic role of CDK4 is barely understood. Using both genetic and pharmacological approaches, we aimed to determine the metabolic role of CDK4 in TNBC cells. Unexpectedly, deletion of CDK4 only slightly reduced triple-negative breast cancer (TNBC) cell proliferation and allowed tumor formationin vivo. Furthermore, proapoptotic stimuli failed to induce appropriate cell death in TNBC cells with CDK4 depletion or long-term CDK4/6 inhibitor treatment. Mechanistically, CDK4 enhances mitochondria-ER contact (MERC) formation, thus promoting mitochondrial fission and ER-mitochondrial calcium signaling. Phosphoproteomic analysis also revealed a role for CDK4 in regulating PKA activity at MERCs to sustain ER-mitochondrial calcium signaling. This proper CDK4-mediated mitochondrial calcium signaling is then required for metabolic flexibility of TNBC cells. Taken together, these results demonstrate that CDK4 inhibition leads to cell death resistance, inhibiting mitochondrial apoptosis and functions through attenuated MERCs formation and ER-mitochondrial calcium signaling in TNBC. Overall, this study provides new insights into the mechanisms of TNBC resistance to CDK4/6i therapy and paves the way to explore potential synergistic therapeutic targeting MERCs-associated metabolic shifts.Graphical Abstract
Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis
Authors: Chew Lindsey A. , Grigsby Daniel , Hester C. Garren , Amason Joshua , McPherson W. Kyle , Flynn Edward J. , Visel Meike , Flannery John G. , Rickman Catherine Bowes 
Published: September 2024

AbstractPatients with both age-related macular degeneration (AMD) and C3 glomerulonephritis (C3G) are challenged by the absence of effective therapies to reverse and eliminate their disease burden. Capitalizing on complement dysregulation as both a significant risk factor for AMD and the known pathophysiology of C3G, we investigated the potential for adeno-associated virus (AAV) delivery of complement factor H (CFH) to rescue C3G in aCfh-/-mouse model of C3G. While past efforts to treat C3G using exogenous human CFH resulted in limited success before immune rejection led to a foreign protein response, our findings demonstrate the capacity for long-term AAV-mediated delivery of truncated CFH (tCFH) to restore inhibition of the alternative pathway of complement and ultimately reverse C3G without immune rejection. Comparing results from the administration of several tCFH vectors also revealed significant differences in their relative efficiency and efficacy. These discoveries pave the way for subsequent development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for a parallel AAV-mediated tCFH gene augmentation therapy for patients with AMD.
Identification and structural characterization of pseudogenes inFusarium graminearum
Authors: Rau Domenico , Posadinu Chiara Maria , Murgia Maria Leonarda , Fois Davide , Porceddu Andrea 
Published: September 2024

ABSTRACTPseudogenes provide valuable insight into the evolutionary history of genomes which can be challenging to ascertain through the examination of functional loci alone. This study presents the findings of a comprehensive, two-step genome-wide survey for the identification and characterization of pseudogenes inFusarium graminearum,the primary causal agent of wheat head blight.By analysing the sequence homology between non-coding regions of the genome and predicted protein sequences, we identified regions with homology to putative paralogous functional sequences. These regions were characterised in terms of their matching sequence structure and position. Most identified pseudogenes were mapped within the fast-evolving genomic compartment and were derived from transposition events. The number of processed and putatively retroposed pseudogenes was found to be comparable. The number of identified pseudogenes was low, which is consistent with the low number of gene duplicates inF. graminearum. No compelling evidence was found to suggest that pseudogene formation can be explained by evolutionary accidents during gene family expansion or as caused by RIP-associated mutagenic events. Notably, about one-third (144/436) of the pseudogenes were found to overlap with untranslated or intron sequences of functional loci, indicating the potential to be transcribed. UsingFusariumcomparative genomics, we identified genomic regions with homology to genes lacking functional orthologs inF. graminearum. These were investigated as putative unitary pseudogenes and, in some cases, their original functions were completely lost after the radiation ofF. graminearum.Interestingly, the paters of 18 loss-of-function pseudogenes showed homology to domains previously identified in proteins involved in pathogenesis.
Quantitative proteomics reveals differential extracellular vesicle cargo from M1 and M2 monocyte-derived human macrophages
Authors: Pantazi Paschalia , Clements Toby , Parsons Harriet T , Kaforou Myrsini , Heesom Kate J , Bennett Phillip R , Guller Seth , Abrahams Vikki M , Holder Beth 
Published: September 2024

AbstractExtracellular vesicles (EVs) mediate intercellular communication by carrying molecular cargo that facilitate diverse physiological processes. Macrophages, playing central roles in immune responses, release EVs that modulate various cellular functions. Given the distinct roles of M1 and M2 macrophage states, understanding the proteomic profiles of their EVs is important for elucidation of EV-mediated signalling and identifying potential biomarkers for diseases involving macrophage polarisation. We employed quantitative proteomics combined with bioinformatics to characterise the proteomic profile of EVs released by M1 and M2 monocyte-derived macrophages. We identified 1,731 proteins in M1/M2 EVs, 132 of which were significantly differentially between M1 and M2. Proteomic data, together with pathway analysis, found that M1/M2 macrophage EV cargo relate to cellular source, and may play roles in shaping immune responses, with M1 EV cargo associated with promotion of pro-inflammatory and antiviral functions, while M2 EV cargo associated with immune regulation and tissue repair. M1 EV cargo was associated with cytokine/chemokine signalling pathways, DNA damage, methylation, and oxidative stress. M2 EV cargo were associated with macrophage alternative-activation signalling pathways, antigen presentation, and lipid metabolism. We also report that macrophage EVs carry metallothioneins, and other related proteins involved in response to metals and oxidative stress.
Bovine dendritic-cell subsets in lymphoid and non-lymphoid tissues: work in progress
Authors: Talker SC , Barut GT , Summerfield A 
Published: September 2024

AbstractBovine dendritic-cell subsets can be readily identified in flow cytometry by staining for Flt3, CD4 and CD13. While this gating strategy could be confirmed by bulk RNA-seq of subsets sorted from peripheral blood mononuclear cells, it remains to be determined if the same gating strategy can be applied to gate on cDC1, cDC2 and pDC within lymphoid and non-lymphoid tissues. With this preprint we aim to inform on the current status of phenotyping experiments performed on Flt3+cells in mesenteric lymph nodes, spleen and lung of cattle. Distinct DC subsets can be gated in all tissues based on CD4 and CD13, with high frequencies of Flt3+CD13+cells (putative cDC1) detected in the lung. Further phenotyping performed on lymph node cells (in particular CADM1, CD26 and CD123) support the subset classification analogous to blood, with pDC being Flt3+CD4+CD13-and cDC1 being Flt3+CD4-CD13+. Heterogeneous expression of CADM1 and CD26 on Flt3+CD4-CD13-putative cDC2 warrants further investigations.
Longitudinal analysis of glioblastoma response to oncolytic HSV1 guides PLX3397 combination for enhanced viral permissiveness
Authors: Ito Hirotaka , Shono Naoyuki , Zagami Claudia , Kim Min J , Quazim Alayo A. , McLaughlin Eric , Goins William F. , Fernandez Soledad , Chiocca E. Antonio , Nakashima Hiroshi 
Published: September 2024

AbstractClinical trial data underscores the need to improve oncolytic virus (OV) distribution within tumors, a challenge compounded by the lack of predictive biomarkers and limited opportunities for post-treatment analysis. To decipher the factors influencing treatment outcomes, we employed multimodal bioluminescence imaging (MM-BLI) in conjunction with magnetic resonance imaging (MRI) to monitor OV infection, replication, and tumor viability in orthotopic brain glioma mouse models. This approach revealed two distinct therapeutic responses: “Responders” with tumor regression and “Non-Responders” with tumor progression. In-depth analysis of individual brains from both groups uncovered dynamic interactions between the OV and the tumor microenvironment, highlighting the involvement of Iba-1+ microglia and tumor necrosis in hindering OV distribution within the tumor. To address this, we incorporated a CSF-1 receptor inhibitor (PLX3397), which improved tumor control by enhancing OV’s direct cytopathic effects and reducing microglial interference. Our findings highlight microglia as a significant barrier to effective OV therapy, suggesting that targeting brain-resident immune cells could enhance the therapeutic efficacy of OVs in resistant brain tumors.
Varying recombination landscapes between individuals are driven by polymorphic transposable elements
Authors: Huang Yuheng , Gao Yi , Ly Kayla , Lin Leila , Lambooij Jan Paul , King Elizabeth G. , Janssen Aniek , Wei Kevin H.-C. , Lee Yuh Chwen G. 
Published: September 2024

AbstractsMeiotic recombination is a prominent force shaping genome evolution, and understanding the causes for varying recombination landscapes within and between species has remained a central, though challenging, question. Recombination rates are widely observed to negatively associate with the abundance of transposable elements (TEs), selfish genetic elements that move between genomic locations. While such associations are usually interpreted as recombination influencing the efficacy of selection at removing TEs, accumulating findings suggest that TEs could instead be the cause rather than the consequence. To test this prediction, we formally investigated the influence of polymorphic, putatively active TEs on recombination rates. We developed and benchmarked a novel approach that uses PacBio long-read sequencing to efficiently, accurately, and cost-effectively identify crossovers (COs), a key recombination product, among large numbers of pooled recombinant individuals. By applying this approach to Drosophila strains with distinct TE insertion profiles, we found that polymorphic TEs, especially RNA-based TEs and TEs with local enrichment of repressive marks, reduce the occurrence of COs. Such an effect leads to different CO frequencies between homologous sequences with and without TEs, contributing to varying CO maps between individuals. The suppressive effect of TEs on CO is further supported by two orthogonal approaches–analyzing the distributions of COs in panels of recombinant inbred lines in relation to TE polymorphism and applying marker-assisted estimations of CO frequencies to isogenic strains with and without transgenically inserted TEs. Our investigations reveal how the constantly changing mobilome can actively modify recombination landscapes, shaping genome evolution within and between species.