bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiment-based computational model predicts that IL-6 classic and trans-signaling exhibit similar potency in inducing downstream signaling in endothelial cells
Authors: Song Min , Wang Youli , Annex Brian H. , Popel Aleksander S. 
Published: September 2023

AbstractInflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as cardiovascular diseases and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, and muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and ERK (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 classic and trans-signaling showed similar potency in inducing downstream signaling; however, trans-signaling induces stronger downstream responses and plays a dominant role in the overall effects from IL-6 due to the in vitro experimental setting of abundant sIL-6R. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the downstream inflammatory and/or angiogenic signals, pSTAT3, pAkt, and pERK responses. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify potential targets that influence IL-6 mediated signaling in endothelial cells and to study their effects quantitatively in modulating STAT3, Akt, and ERK activation.
Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation
Authors: Bernabé-Rubio Miguel , Ali Shahnawaz , Bhosale Priyanka G. , Goss Georgina , Mobasseri Seyedeh Atefeh , Tapia-Rojo Rafael , Zhu Tong , Hiratsuka Toru , Battilocchi Matteo , Tomás Inês M. , Ganier Clarisse , Garcia-Manyes Sergi , Watt Fiona M. 
Published: September 2023

AbstractDedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing to uncover the underlying mechanism. Gata6-lineage positive and negative epidermal stem cells in wounds are transcriptionally indistinguishable. Furthermore, in contrast to reprogramming of induced pluripotent stem cells, the same genes are expressed in the epidermal dedifferentiation and differentiation trajectories, indicating that dedifferentiation does not involve adoption of a new cell state. We demonstrate that dedifferentiation is not only induced by wounding, but also by retinoic acid treatment or mechanical expansion of the epidermis. In all three cases, dedifferentiation is dependent on the master transcription factor c-Myc. Mechanotransduction and actin-cytoskeleton remodelling are key features of dedifferentiation. Our study elucidates the molecular basis of epidermal dedifferentiation, which may be generally applicable to adult tissues.
Warming beneath an East Antarctic ice shelf due to increased subpolar westerlies and reduced sea ice
Authors: Lauber Julius , Hattermann Tore , de Steur Laura , Darelius Elin , Auger Matthis , Nøst Ole Anders , Moholdt Geir 
Published: September 2023

AbstractUnderstanding how climate change influences ocean-driven melting of the Antarctic ice shelves is one of the greatest challenges for projecting future sea level rise. The East Antarctic ice shelf cavities host cold water masses that limit melting, and only a few short-term observational studies exist on what drives warm water intrusions into these cavities. We analyse nine years of continuous oceanographic records from below Fimbulisen and relate them to oceanic and atmospheric forcing. On monthly time scales, warm inflow events are associated with weakened coastal easterlies reducing downwelling in front of the ice shelf. Since 2016, however, we observe sustained warming, with inflowing Warm Deep Water temperatures reaching above 0 °C. This is concurrent with an increase in satellite-derived basal melt rates of 0.62 m yr−1, which nearly doubles the basal mass loss at this relatively cold ice shelf cavity. We find that this transition is linked to a reduction in coastal sea ice cover through an increase in atmosphere–ocean momentum transfer and to a strengthening of remote subpolar westerlies. These results imply that East Antarctic ice shelves may become more exposed to warmer waters with a projected increase of circum-Antarctic westerlies, increasing this region’s relevance for sea level rise projections.
APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer
Authors: McCann Jennifer L. , Cristini Agnese , Law Emily K. , Lee Seo Yun , Tellier Michael , Carpenter Michael A. , Beghè Chiara , Kim Jae Jin , Sanchez Anthony , Jarvis Matthew C. , Stefanovska Bojana , Temiz Nuri A. , Bergstrom Erik N. , Salamango Daniel J. , Brown Margaret R. , Murphy Shona , Alexandrov Ludmil B. , Miller Kyle M. , Gromak Natalia , Harris Reuben S. 
Published: September 2023

AbstractThe single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.
Modeling policy interventions for slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda
Authors: Zupko Robert J. , Nguyen Tran Dang , Ngabonziza J. Claude S. , Kabera Michee , Li Haojun , Tran Thu Nguyen-Anh , Tran Kien Trung , Uwimana Aline , Boni Maciej F. 
Published: September 2023

AbstractArtemisinin combination therapies (ACTs) are highly effective at treating uncomplicated Plasmodium falciparum malaria, but the emergence of the new pfkelch13 R561H mutation in Rwanda, associated with delayed parasite clearance, suggests that interventions are needed to slow its spread. Using a Rwanda-specific spatial calibration of an individual-based malaria model, we evaluate 26 strategies aimed at minimizing treatment failures and delaying the spread of R561H after 3, 5 and 10 years. Lengthening ACT courses and deploying multiple first-line therapies (MFTs) reduced treatment failures after 5 years when compared to the current approach of a 3-d course of artemether–lumefantrine. The best among these options (an MFT policy) resulted in median treatment failure counts that were 49% lower and a median R561H allele frequency that was 0.15 lower than under baseline. New approaches to resistance management, such as triple ACTs or sequential courses of two different ACTs, were projected to have a larger impact than longer ACT courses or MFT; these were associated with median treatment failure counts in 5 years that were 81–92% lower than the current approach. A policy response to currently circulating artemisinin-resistant genotypes in Africa is urgently needed to prevent a population-wide rise in treatment failures.
Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus
Authors: Tossell Kyoko , Yu Xiao , Giannos Panagiotis , Anuncibay Soto Berta , Nollet Mathieu , Yustos Raquel , Miracca Giulia , Vicente Mikal , Miao Andawei , Hsieh Bryan , Ma Ying , Vyssotski Alexei L. , Constandinou Tim , Franks Nicholas P. , Wisden William 
Published: September 2023

AbstractThe prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be ‘tiredness’. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFCSst-GABA) cells that responded to sleep deprivation. These cells projected to the lateral preoptic (LPO) hypothalamus and the lateral hypothalamus (LH). Stimulating PFCSst-GABA terminals in the LPO hypothalamus caused sleep-preparatory behavior (nesting, elevated theta power and elevated temperature), and stimulating PFCSst-GABA terminals in the LH mimicked recovery sleep (non-rapid eye-movement sleep with higher delta power and lower body temperature). PFCSst-GABA terminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse cells in the LPO hypothalamus and the LH. The PFC also might feature in deciding sleep location in the absence of excessive fatigue. These findings suggest that the PFC instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.
Organ-oriented proteogenomics functional atlas of three aquatic invertebrate sentinel species
Authors: Leprêtre Maxime , Degli Esposti Davide , Sugier Kevin , Espeyte Anabelle , Gaillard Jean-Charles , Delorme Nicolas , Duflot Aurélie , Bonnard Isabelle , Coulaud Romain , Boulangé-Lecomte Céline , Xuereb Benoît , Palos Ladeiro Mélissa , Geffard Alain , Geffard Olivier , Armengaud Jean , Chaumot Arnaud 
Published: September 2023

AbstractProteogenomic methodologies have enabled the identification of protein sequences in wild species without annotated genomes, shedding light on molecular mechanisms affected by pollution. However, proteomic resources for sentinel species are limited, and organ-level investigations are necessary to expand our understanding of their molecular biology. This study presents proteomic resources obtained from proteogenomic analyses of key organs (hepatopancreas, gills, hemolymph) from three established aquatic sentinel invertebrate species of interest in ecotoxicological/ecological research and environmental monitoring: Gammarus fossarum, Dreissena polymorpha, and Palaemon serratus. Proteogenomic analyses identified thousands of proteins for each species, with over 90% of them being annotated to putative function. Functional analysis validated the relevance of the proteomic atlases by revealing similarities in functional annotation of catalogues of proteins across analogous organs in the three species, while deep contrasts between functional profiles are delimited across different organs in the same organism. These organ-level proteomic atlases are crucial for future research on these sentinel animals, aiding in the evaluation of aquatic environmental risks and providing a valuable resource for ecotoxicological studies.
The difference between two brachycephalic and one mesocephalic dog breeds’ problem-solving performance suggests evidence for paedomorphism in behaviour
Authors: Ujfalussy Dorottya Júlia , Bognár Zsófia , Molnár Marianna , Miklósi Ádám , Kubinyi Enikő 
Published: September 2023

AbstractDespite serious health and longevity problems, small brachycephalic breeds are becoming increasingly popular among pet owners. Motivations for choosing short-nosed breeds have been extensively investigated in recent years; however, this issue has been addressed mainly by relying on owner reports, resulting in explanations of “cute looks”, referring to the baby-schema phenomenon and “behaviour well suited for companionship”. We aimed to compare the behaviour of two brachycephalic (English and French bulldogs) and one mesocephalic (Mudi) breed in a problem-solving context. The dogs were given the task of opening boxes containing food rewards. We investigated human-directed behaviour elements over success and latency (indicators of motivation and ability). We found that both English and French bulldogs were significantly less successful in solving the problem than mudis. Both brachycephalic breeds had longer opening latencies than the mesocephalic breed. Brachycephalic breeds oriented less at the problem box and more at humans present. In summary, the short-headed breeds were less successful but oriented much more toward humans than mesocephalic dogs. Owners might interpret these behaviours as “helplessness” and dependence. The results support the hypothesis that infant-like traits may be present not only in appearance but also in behaviour in brachycephalic breeds, eliciting caring behaviour in owners.
Effects of lactotripeptide ingestion and physical activity intervention on the fatigue status of middle-aged and older adults: a randomized controlled trial
Authors: Yoshioka Masaki , Kaneko Tomoko , Yoneko Karen , Matsui Masahiro , Mori Shoya , Nishitani Natsumi , Wenxing Qin , Ouchi Kei , Yasuda Risa , Namatame Hayate , Sato Tomohito , Park Jiyeon , Nakata Yoshio , Maeda Seiji , Kosaki Keisei 
Published: September 2023

AbstractThis randomized controlled trial aimed to investigate the effects of eight weeks of lactotripeptide (LTP) ingestion, physical activity (PA) intervention, and combined intervention on the fatigue status of middle-aged and older adults. A total of 78 middle-aged and older adults (63 ± 8 years of age) were randomly assigned to four groups: placebo, LTP, placebo with PA intervention (placebo + PA), and LTP with PA intervention (LTP + PA). All participants ingested the placebo or LTP tablets daily (three tablets/day). The placebo + PA and LTP + PA groups participated in a weekly supervised exercise class and were instructed to increase their moderate- to vigorous-intensity PA at home. The visual analog scale, Brief Fatigue Inventory, Profile of Mood States second edition (POMS2), and Beck Depression Inventory second edition (BDI-II) were administered before and after the intervention. No significant interactions or main effects were observed between LTP ingestion and PA intervention on any of the fatigue scales. The main-effect analyses revealed that the PA intervention improved the total mood disturbance score of the POMS2 (F = 5.22, P = 0.03) and BDI-II score (F = 4.81, P = 0.03). After the post hoc paired comparisons, the total mood disturbance and BDI-II scores improved more with the combined intervention than with the PA intervention alone (percentage difference between the effect of combined intervention and PA intervention alone was 3.7% for total mood disturbance score and 13.7% for BDI-II score). The present study suggests that eight weeks of LTP ingestion and PA intervention did not have a significant effect on fatigue status. However, the PA intervention improved mood status and depressive symptoms, and these effects were enhanced by LTP ingestion.
Ankle stiffness asymmetry is associated with balance function in individuals with chronic stroke
Authors: Kim Hogene , Cho Jieun , Cho Sangwoo , Shin Joon-Ho 
Published: September 2023

AbstractAnkle joint is one of important contributors on balance in stroke survivors. This study aimed to investigate the relationships of ankle stiffness symmetry ratios along the talocrural and subtalar axes with clinical balance measures and weight distribution during quiet standing in ambulatory chronic post-stroke survivors. The clinical trials involved 15 ambulatory elderly with chronic post-stroke hemiparesis and 15 healthy controls. Ankle stiffness was evaluated during non-weight-bearing isokinetic passive biaxial ankle movements, and ankle stiffness symmetry ratios between paretic and non-paretic ankle stiffness (SR: Inversion/Eversion SRIE& Dorsi-/Plantarflexion SRDP) were measured. A certified physiotherapist evaluated the Berg Balance Scale (BBS) and weight-distribution ratio (WDR) on bilateral force plates during quiet standing. Correlation coefficients, the factor analysis, and Pearson linear multiple regression were assessed with measured parameters. Correlation coefficients showed significances in-betweens; BBS and SRDP(r = −0.543, p = 0.022), WDR and SRIE(r = −0.667, p = 0.004), SRIEand SRDP(r = −0.604, p = 0.011). The exploratory factor analysis suggested four extracted factors; (1) Balance & Gait, (2) Stroke, (3) Symmetry and (4) Dimension. The first and second factors include general and pathological characteristics in stoke participants respectively. The third factor is associated with symmetrical characteristics explaining up to 99.9% of the variance. Multiple regression analysis showed ankle stiffness ratios predict BBS up to 60% of variance. The biaxial ankle stiffness ratio is a useful clinical variable that assesses balance function, in ambulatory chronic stroke survivors.
Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis
Authors: He Xianghua , Yang Jian , Feng Jiaming , Huang Hongyan , Dong Xiaolin , Zhao Quanzhen , Shen Qiuyan , Hu Caiyou , Xu Yanming 
Published: September 2023

AbstractThis study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.
Multi-isotope analysis of bone collagen of Late Pleistocene ungulates reveals niche partitioning and behavioural plasticity of reindeer during MIS 3
Authors: Britton Kate , Jimenez Elodie-Laure , Le Corre Mael , Renou Sylvain , Rendu William , Richards Michael P. , Hublin Jean-Jacques , Soressi Marie 
Published: September 2023

AbstractHere we present stable carbon, nitrogen and sulfur isotope ratios of collagen extracted from Rangifer, Equus and Bison bone (n = 128) from different stratigraphic levels at the chronologically well-constrained Middle and Upper Palaeolithic site of Les Cottés, France. Samples were taken from five phases of site use (US08, US06, US04 [upper and lower], and US02; ~ 45.8–35.3 ka cal BP) to explore the dietary and spatial palaeoecology of these ungulate species during MIS 3, and the contemporary climate. Temporal trends in δ15N values of all species broadly align with other climatic indicators at the site and the lowest values in US04 correspond to the Heinrich 4 cooling event, reflecting changes in the composition of soil/plant nitrogen at this time. Rangifer collagen is 13C-enriched compared to the other species throughout, consistent with lichen consumption. However, this isotopic niche partitioning between Rangifer and Equus/Bison is most extensive during US04, indicating plasticity in reindeer feeding behaviour, and potentially overall increased lichen biomass during this cooler/more arid phase. Rangifer δ34S values are consistently lower than Equus and Bison, which could be indicative of their more extensive spatial ranges incorporating greater inland areas. Equus and Bison demonstrate a significant decrease in δ34S values through time, which may be linked to contemporary climatic decline.
Neuromas cause severe residual problems at long-term despite surgery
Authors: Dahlin Emma , Gudinge Hanna , Dahlin Lars B. , Nyman Erika 
Published: September 2023

AbstractPain, and disabilities after neuroma surgery, using patient reported outcome measurements (PROMs), were evaluated by QuickDASH and a specific Hand Questionnaire (HQ-8). The 69 responding individuals (response rate 61%; 59% women; 41% men; median follow up 51 months) reported high QuickDASH score, pain on load, cold sensitivity, ability to perform daily activities and sleeping difficulties. Individuals reporting impaired ability to perform daily activities and sleeping problems had higher scores for pain, stiffness, weakness, numbness/tingling, cold sensitivity and QuickDASH. Only 17% of individuals reported no limitations at all. No differences were observed between sexes. Surgical methods did not influence outcome. Symptoms and disabilities correlated moderately-strongly to each other and to ability to perform regular daily activities as well as to sleeping difficulties. Pain, cold sensitivity, sleeping difficulties and limitation to perform daily activities were associated to higher QuickDASH. A weak association was found between follow up time and QuickDASH score as well as pain on load, but not cold sensitivity. A major nerve injury was frequent among those with limitations during work/performing other regular daily activities. Despite surgical treatment, neuromas cause residual problems, which affect the capacity to perform daily activities and ability to sleep with limited improvement in long-term.