bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroplast genome editing of Rubisco boosts photosynthesis and plant growth
Authors: Yamori Wataru , Nakazato Issei , Yuchen Qu , Sanga Yukina , Miyata Tomoko , Uehara Ryo , Noto Yuma , Namba Keiichi , Fukayama Hiroshi , Matsumura Hiroyoshi , Arimura Shin-ichi 
Published: January 2025

AbstractPhotosynthetic inefficiencies limit the productivity and sustainability of crop production and the resilience of agriculture to future societal and environmental challenges. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) has inherently low catalytic efficiency, making it a key target for photosynthesis and crop improvement. However, introducing mutations to the chloroplast-encoded Rubisco large subunit (rbcL), which contains the enzyme’s catalytic sites, is technically challenging. In this study, we successfully generated a range of chloroplast-genome-editedArabidopsis thalianaplants targetingrbcLby a targeted base editor, ptpTALECD. The M309I and D397N substitutions inrbcLresulted in an increased Rubisco catalytic rate (kcat) without any reductions of Rubisco content, thereby enhancing photosynthetic rates and plant growth under both current atmospheric CO2concentrations (i.e., 381 μmol mol−1) and projected future concentrations (i.e., 549 μmol mol−1). Cryo-electron microscopy (cryo-EM) structural analysis showed that the M309I and D397N substitutions, although located far from the catalytic site, induce structural alterations in the catalytic (60s) loops. Our findings highlight the potential of Rubisco engineering to improve plant photosynthesis and growth, and underscore the unique opportunities that chloroplast genome editing offers for enhancing photosynthesis and crop productivity and reducing atmospheric CO2levels in a non-GMO context.
Role of Cockayne Syndrome B (CSB) Protein in Genome Maintenance in Human Cells under Oxidative Stress
Authors: Low Grace Kah Mun , Ng Gavin Yong-Quan , Zeegers Dimphy , Ting Aloysius , Gopalakrishnan Kalpana , Khaw Aik Kia , Jayapal Manikandan , Hande M Prakash 
Published: January 2025

AbstractCockayne Syndrome (CS), a disorder marked by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a critical component of the transcription-coupled repair pathway of nucleotide excision repair. This study explores the role of CSB in managing oxidative DNA damage and maintaining telomere integrity under oxidative stress conditions. We subjected CSB-deficient human fibroblasts (CS-B) and control fibroblasts to acute and chronic oxidative stress through hydrogen peroxide (H₂O₂) treatment and elevated oxygen levels. Our findings reveal that CS-B fibroblasts exhibit a distinct resistance to acute oxidative stress, as evidenced by their sustained viability and minimal cell cycle arrest compared to control fibroblasts. However, chronic oxidative conditions led to accelerated senescence in CS-B fibroblasts, demonstrated by increased telomere attrition rates, senescent morphology, and upregulated senescence-associated β-galactosidase activity. Further, gene expression analysis post-H₂O₂ exposure identified the downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts, suggesting a compromised ability to respond to oxidative DNA damage. These observations underscore the multifaceted role of CSB in genomic maintenance and highlight its potential involvement in the pathology of CS through impaired response to oxidative stress and telomere instability. The study contributes to a deeper understanding of the cellular mechanisms that underlie CS symptoms and may inform potential therapeutic strategies targeting oxidative damage repair systems.
Brain Infiltrated Monocyte-Macrophages in a rat model of Temporal Lobe Epilepsy: Revisiting the Pro-Inflammatory Paradigm
Authors: Grabon Wanda , Gasmi Nadia , Lang Anatole , Ruiz Anne , Georges Béatrice , Blot Victor , Ogier Michaël , Rheims Sylvain , Navarro Fabrice P , Bezin Laurent 
Published: January 2025

ABSTRACTNeuroinflammation is central to temporal lobe epilepsy, yet the specific role of myeloid cells remains unclear. In status epilepticus (SE) models, circulating monocytes have been reported to infiltrate the brain, though distinguishing them from microglia remains challenging. Using a rat model, we traced infiltrating monocytes post-SE, to investigate their persistence, phenotypic evolution during epileptogenesis and contribution to neuroinflammation. By tracking phagocyted fluorescent nanoparticles and using CD68 immunohistochemistry, we confirmed that monocytes entered the brain in significant numbers 24 hours post-SE, after the inflammatory peak occurred (7h post-SE). Tracked up to 7 weeks, these cells adopted a microglia-like phenotype, contributed to the microglial scar and sustained low-grade inflammation during the chronic phase of epilepsy solely through their presence, as their expression of pro-inflammatory markers resembled that of non-activated microglia. Importantly, monocytes initially and transiently supported an anti-inflammatory response providing a unique opportunity to modulate neuroinflammation and potentially disrupt epilepsy progression, opening new avenues for therapeutic interventions.
Localized Reconstruction of Multimodal Distance Distribution from DEER Data of Biopolymers
Authors: Tsay Karen , Keller Timothy , Fichou Yann , Freed Jack H. , Han Song-I , Srivastava Madhur 
Published: January 2025

ABSTRACTPulsed Dipolar ESR Spectroscopy (PDS) is a uniquely powerful technique to characterize the structural property of intrinsically disordered proteins (IDPs) and polymers and the conformational evolution of IDPs and polymers, e.g. during assembly, by offering the probability distribution of segment end-to-end distances. However, it is challenging to determine distance distributionP(r) of IDPs by PDS because of the uncertain and broad shape information that is intrinsic to the distance distribution of IDPs. We demonstrate here that the Srivastava-Freed Singular Value Decomposition (SF-SVD) point-wise mathematical inversion method along with wavelet denoising (WavPDS) can aid in obtaining reliable shapes for the distance distribution,P(r), for IDPs. We show that broad regions ofP(r) as well as mixed narrow and broad features within the captured distance distribution range can be effectively resolved and differentiated withouta prioriknowledge. The advantage of SF-SVD and WavPDS is that the methods are transparent, requiring no adjustable parameters, the processing of the magnitude for the probability distribution is performed separately for each distance increment, and the outcome of the analysis is independent of the user’s judgement. We demonstrate the performance and present the application of WavPDS and SF-SVD on model ruler molecules, model polyethylene glycol polymers with end-to-end spin labeling, and IDPs with pairwise labeling spanning different segments of the protein tau to generate the transparent solutions to theP(r)’s including their uncertainties and error analysis.
Sex-specific Associations of Gene Expression with Alzheimer’s Disease Neuropathology and Ante-mortem Cognitive Performance
Authors: Seto Mabel , Clifton Michelle , Gomez Melisa Lara , Coughlan Gillian , Gifford Katherine A. , Jefferson Angela L. , De Jager Philip L. , Bennett David A , Wang Yanling , Barnes Lisa L. , Schneider Julie A , Hohman Timothy J. , Buckley Rachel F. , Dumitrescu Logan 
Published: January 2025

AbstractThe biological mechanisms underlying women’s increased Alzheimer’s disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition. Of 23,118 significant gene associations, 10% were significant in one sex and not the other (sex-specific). Most sex-specific gene associations were identified in females (73%) and associated with tau tangles and longitudinal cognition (90%). Four X-linked genes,MCF2,HDAC8,FTX, andSLC10A3, demonstrated significant sex differences in their associations with AD endophenotypes (i.e., significantsex x geneinteraction). Our results also uncovered sex-specific biological pathways, including a female-specific role of neuroinflammation and neuronal development, reinforcing the potential for sex-aware analyses to enhance precision medicine approaches in AD.
Reducing Cofilin dosage makes embryos resilient to heat stress
Authors: Biel Natalie , Rashid Faizan , Natua Subhashis , Wang Ting-Yu , Chou Tsui-Fen , Nguyen Thu Vu Phuc , Golding Ido , Kalsotra Auinash , Sokac Anna Marie 
Published: January 2025

AbstractIn addition to regulating the actin cytoskeleton, Cofilin also senses and responds to environmental stress. Cofilin can promote cell survival or death depending on context. Yet, many aspects of Cofilin’s role in survival need clarification. Here, we show that exposing earlyDrosophilaembryos to mild heat stress (32°C) induces a Cofilin-mediated Actin Stress Response and upregulation of heat- and ER-stress response genes. However, these responses do not alleviate the negative impacts of heat exposure. Instead, heat stressed embryos show downregulation of hundreds of developmental genes, including determinants of the embryonic body plan, and are less likely to hatch as larvae and adults. Remarkably, reducing Cofilin dosage blunts induction of all stress response pathways, mitigates downregulation of developmental genes, and completely rescues survival. Thus, Cofilin intersects with multiple stress response pathways, and modulates the transcriptomic response to heat stress. Strikingly, Cofilin knockdown emerges as a potent pro-survival manipulation for embryos.
Prairie management practices influence biodiversity, productivity and surface-atmosphere feedbacks
Authors: Wang Ran , Gamon John A. , Hogan Katharine F. E. , Kellar P. Roxanne , Wedin David A. 
Published: January 2025

SummaryRestoration efforts aim to reestablish grassland cover and maintain ecosystem services. However, there is a lack of systematic evaluation of the effects of grassland restoration options on integrated biodiversity, carbon, ecosystem function, and climate feedbacks.Through a multi-year grassland restoration experiment in a tallgrass prairie site in Nebraska, USA, we investigated how different management practices affected biodiversity, productivity and the surface-atmosphere feedbacks using a combination of in situ measurements and airborne hyperspectral and thermal remote sensing.Our findings suggested that certain management treatments altered species diversity, productivity and energy balance. Higher diversity plots had higher vegetation cover, albedo, canopy water content and lower surface temperature, indicating clear effects of management treatments on grassland ecosystem processes influencing surface-atmosphere feedbacks of mass and energy.The coherent responses of multiple airborne remote sensing indices illustrate clear co-benefits of grassland restoration practices that enhance ecosystem productivity and biodiversity and mitigate climate change through surface atmosphere feedbacks, offering a new strategy to address the global challenges of biodiversity loss and climate change in prairie ecosystems.
TGF-β3 Promotes Trophoblast Development via ACSS2-Dependent Permissive Lipid Metabolism
Authors: Boffa Francesca , Moncada Margherita , Sterzo Martina Lo , Palazzese Luca , Scuderi Aaurora , Domenicone Marika , Capra Emanuele , Lazzari Barbari , Gioia Luisa , Alberio Ramiro , Iuso Domenico , Loi Pasqualino , Czernik Marta 
Published: January 2025

AbstractTransforming growth factor-beta (TGF-β) supports the in vitro maintenance of embryonic and trophoblast stem cells. Here, we demonstrated that, in a sheep embryo model, the transition from morula to blastocyst is positively regulated by TGF-β3, primarily through its promotion of trophoblast development. Our results indicate that morulae treated with TGF-β3 develop at a higher rate into blastocysts, characterized by an expanded trophoblast layer marked by CDX-2 expression. In blastocysts, TGF-β3 mediates transcriptional activation of genes involved in cell adhesion and lipid metabolism pathways, leading to remarkable in vitro outgrowth expansion and a substantial increase in trophoblast lipid droplet content. Functional analysis reveal that the positive effects of TGF-β3 are mitigated by inhibition of Acetyl-CoA Synthetase Short-Chain Family Member 2 (ACSS2), a key enzyme upregulated by TGF-β3 and a promoter of de novo lipgenensis. These findings suggest that TGF-β3 modulates lipid metabolism during blastocyst formation and may play a potential role in regulating implantation and placental development.
Niche construction: the case of industrial vinegar production
Authors: Smith Reginald D. 
Published: January 2025

AbstractNiche construction is the process by which changes made to an environment by organisms also in turn drive their own evolution. While many examples of niche construction in the wild or human societies have been described, it is rare that a clear example of niche construction in an environment under human control can be demonstrated. Industrial vinegar production is a fermentation conducted by acetic acid bacteria. Importantly, the acetic acid bacteria produce acetic acid whose increasing acidity selects out acetic acid bacteria with lower tolerances for acidity. The remaining acetic acid bacteria continue to produce higher levels of acidity causing a directional selection that drives the acidity tolerance of the overall population higher while reducing the population’s genetic diversity. This niche construction will be described and modeled and its implications for the probable self-limiting constraints of niche construction in wild populations is discussed.
Ancient DNA reveals diverse community organizations in the 5th millennium BCE Carpathian Basin
Authors: Szécsényi-Nagy Anna , Virag Cristian , Jakab Kristóf , Rohland Nadin , Ringbauer Harald , Anders Alexandra , Raczky Pál , Hajdu Tamás , Kiss Krisztián , Szeniczey Tamás , Évinger Sándor , Keszi Tamás , Virág Zsuzsanna M. , Cheronet Olivia , Mallick Swapan , Akbari Ali , Pinhasi Ron , Reich David , Siklósi Zsuzsanna 
Published: January 2025

AbstractWe present a comprehensive genetic investigation of Late Neolithic (LN) and Early Copper Age (ECA) populations living in the Carpathian Basin, leveraging whole genome data from 125 previously unreported individuals. Using population genetics, kinship analyses and the study of networks of identity-by-descent haplotype segment sharing, we elucidate the social and genetic dynamics of these communities between 4800-3900 cal BCE. Despite changes in settlement patterns, burial practices, and material culture, we document a high degree of genetic continuity. While one set of individuals we analyzed from a large community cemetery was genetically diverse, another site was more homogenous and closed, with numerous consanguineous relationships and evidence of patrilineality and patrilocality. These results document radically different kinship systems in contemporaneous ECA communities using similar material culture and living only about 100 km apart.
Changing Pattern of Paediatric Endocrinology Referrals over two decades: A Retrospective Study from a Tertiary Centre in Western India
Authors: Vaman Khadilkar , Bhade Karishma K. , Wagle-Patki Sonali , Khadilkar Anuradha V. 
Published: January 2025

AbstractIntroductionUnderstanding the paediatric endocrinology referral pattern is important for primary care clinicians and paediatric endocrinologists to optimise patient care, facilitate continuous medical education and to upgrade resources. This study analysed the pattern of these referrals over a year, the change in referral trends 2 decades apart and the discrepancy between the referral reasons and final diagnoses.MethodsA retrospective analysis was conducted on demographic details and referral reasons to paediatric endocrine clinic in a tertiary care hospital in Western India at 2-time intervals 2 decades apart (2002-03 and 2022-23). The referral reasons were categorised into 14 classes as per International classification of paediatric endocrinology diagnoses (ICPED) 2016.ResultsData of 2595 patients (920 from 2002-03 and 1675 from 2022-23) was studied. The commonest reason for referral was Short Stature with no gender bias. Disorders of Puberty and Obesity were the 2nd and 3rd commonest reasons for referral. There was almost a 2-fold rise in the total number of referrals over 2 decades with a significant rise in females referred for Short Stature and Disorders of Puberty. There was a discrepancy between the final diagnosis and referral reason, predominantly in patients referred for Micropenis, Gynaecomastia and ObesityConclusionWe report paediatric endocrine referral pattern over two decades, revealing a shift in the number of referrals but not a major shift in the referral reasons. A gap exists in recognizing symptoms and possible cause at the primary care level. These findings highlight the need for focused medical education and awareness among primary care clinicians.
Modeling tumor dynamics and predicting response to chemo-, targeted-, and immune-therapies in a murine model of pancreatic cancer
Authors: Vishwanath Krithik , Choi Hoon , Gupta Mamta , Zhou Rong , Sorace Anna G. , Yankeelov Thomas E. , Lima Ernesto A.B.F. 
Published: January 2025

AbstractWe seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of the response of pancreatic cancer to the NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, and cisplatin), stromal-targeting drugs (calcipotriol and losartan), and an immune checkpoint inhibitor (anti-PD-L1). We developed a set of ordinary differential equations describing changes in tumor size (growth and regression) under the influence of five cocktails of treatments. Model calibration relies on three tumor volume measurements obtained over a 14-day period in a genetically engineered pancreatic cancer model (KrasLSLG12D-Trp53LSLR172H-Pdx1-Cre). Our model reproduces tumor growth in the control and treatment scenarios with an average concordance correlation coefficient (CCC) of 0.99±0.01. We conduct leave-one-out predictions (average CCC=0.74±0.06), mouse-specific predictions (average CCC=0.75±0.02), and hybrid, group-informed, mouse-specific predictions (average CCC=0.85±0.04). The developed mathematical model demonstrates high accuracy in fitting the experimental tumor data and a robust ability to predict tumor response to treatment. This approach has important implications for optimizing combination NGC treatment strategies.
Embodiment of a functionally altered virtual arm in children and adults
Authors: Johannsen Leif , Pi Claire Yuke , Thurlbeck Simon , Gilles Marco , Pan Sylvia Xueni , Cowie Dorothy 
Published: January 2025

AbstractThis study aimed to investigate whether human embodiment is dependent on the sensorimotor functions of one’s body. We hypothesised that body function constrains both the sense of ownership and sensorimotor control of the body movements. We studied these relationships in the context of control of unilateral goal-directed forward arm reaching movements made with a virtual arm. In addition, we expected that children possess more adaptable body representations compared to adults, facilitating greater acceptance of virtual bodies with altered sensorimotor contingencies. We tested 5-7 and 8-10-year-old children, and young adults. Participants took part in an animal feeding game within a Virtual Reality environment. At each age, we manipulated the visual gain of hand movements to alter reaching functionality in three groups: compared to a normal (100%) gain, reaching arm length was slightly reduced (80%); slightly increased (120%); or greatly increased (400%). Parameters representing reach kinematics, subjective perception of arm length, and subjective limb embodiment were assessed during and after reaching with normal and altered control gain. In addition to changes in their reach kinematics, changes in subjective embodiment and reaching affordance were recorded compared to baseline reaching without altered visual gain. We found that the altered reaching functionality reduced Subjective ratings of limb ownership during exposure to the 400% visual gain modification in the group of adults only. In contrast, changes in reach kinematics occurred in all the age groups of children and adults, with age group-specific adjustments in the motor control strategy, characterised by altered magnitude and spatiotemporal placement of peak velocity as well as smoothness of reaching. Finally, at all ages subjective reaching affordance estimates were enhanced following exposure to the two functionality conditions with increased arm length. Our results indicate that the sense of ownership, accuracy of body representations, and characteristics of sensorimotor control are related to bodily function. In addition, it appears that these relationships might be more plastic, or perhaps more tolerant to functional alterations in terms of perceived ownership, in children compared to adults.
Nucleus softens during herpesvirus infection
Authors: Tervonen Aapo , Leclerc Simon , Ruokolainen Visa , Tieu Katie , Lyonnais Sébastien , Niskanen Henri , Chen Jian-Hua , Gupta Alka , Kaikkonen Minna U , Larabell Carolyn A , Muriaux Delphine , Mattola Salla , Conway Daniel E , Ihalainen Teemu O , Aho Vesa , Vihinen-Ranta Maija 
Published: January 2025

ABSTRACTMechanical properties of the nucleus are remodeled not only by extracellular forces transmitted to the nucleus but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the viral regulation of essential nuclear functions and growth of the nuclear viral replication compartments are known to reorganize nuclear structures. However, little is known about how this infection-induced nuclear deformation changes nuclear mechanobiology. Our analyses showed that the nucleus softens during the infection. To understand why this happens, we used microscopy and computational methods to study how the mechanical components of the nucleus are modified during the infection. We discovered that the viral replication compartment occupying the nuclear center has a low biomolecular density compared to the centrally located euchromatin in noninfected cells. The nuclear lamina was also modified such that in the infection the amount of lamin proteins increased and the nuclear envelope had more outward curved regions and moved less in infection compared to noninfected cells. The computational modeling of virus-induced changes in cellular forces showed that the most probable cause for the decreasing nuclear stiffness is the removal of lamina-associated domains or the decrease in outward forces, such as reduced intranuclear osmotic pressure and cytoskeletal pull. The simulations showed that an increase in the nuclear envelope tension can occur with a decrease in nuclear stiffness. Based on these findings, we propose a mechanical model that explains mechanistic coordination between the nuclear deformation in infection and decreased nuclear stiffness.