bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Do People Generalize Causal Relations over Objects? A Non-parametric Bayesian Account
Authors: Zhao Bonan , Lucas Christopher G. , Bramley Neil R. 
Published: November 2021

AbstractHow do people decide how general a causal relationship is, in terms of the entities or situations it applies to? What features do people use to decide whether a new situation is governed by a new causal law or an old one? How can people make these difficult judgments in a fast, efficient way? We address these questions in two experiments that ask participants to generalize from one (Experiment 1) or several (Experiment 2) causal interactions between pairs of objects. In each case, participants see an agent object act on a recipient object, causing some changes to the recipient. In line with the human capacity for few-shot concept learning, we find systematic patterns of causal generalizations favoring simpler causal laws that extend over categories of similar objects. In Experiment 1, we find that participants’ inferences are shaped by the order of the generalization questions they are asked. In both experiments, we find an asymmetry in the formation of causal categories: participants preferentially identify causal laws with features of the agent objects rather than recipients. To explain this, we develop a computational model that combines program induction (about the hidden causal laws) with non-parametric category inference (about their domains of influence). We demonstrate that our modeling approach can both explain the order effect in Experiment 1 and the causal asymmetry, and outperforms a naïve Bayesian account while providing a computationally plausible mechanism for real-world causal generalization.
Genetic background in late-onset sensorineural hearing loss patients
Authors: Uehara Natsumi , Fujita Takeshi , Yamashita Daisuke , Yokoi Jun , Katsunuma Sayaka , Kakigi Akinobu , Nishio Shin-ya , Nibu Ken-ichi , Usami Shin-ichi 
Published: November 2021

AbstractGenetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.
Oxidative damage-induced hyperactive ribosome biogenesis participates in tumorigenesis of offspring by cross-interacting with the Wnt and TGF-β1 pathways in IVF embryos
Authors: Huang Yue , Li Zhiling , Lin En , He Pei , Ru Gaizhen 
Published: November 2021

AbstractIn vitro fertilization (IVF) increases the risk of tumorigenesis in offspring. The increased oxidative damage during IVF may be involved in tumor formation. However, the molecular mechanisms underlying this phenomenon remain largely unclear. Using a well-established model of oxidatively damaged IVF mouse embryos, we applied the iTRAQ method to identify proteins differentially expressed between control and oxidatively damaged zygotes and explored the possible tumorigenic mechanisms, especially with regard to the effects of oxidative damage on ribosome biogenesis closely related to tumorigenesis. The iTRAQ results revealed that ribosomal proteins were upregulated by oxidative stress through the Nucleolin/β-Catenin/n-Myc pathway, which stimulated ribosomes to synthesize an abundance of repair proteins to correct the damaged DNA/chromosomes in IVF-derived embryos. However, the increased percentages of γH2AX-positive cells and apoptotic cells in the blastocyst suggested that DNA repair was insufficient, resulting in aberrant ribosome biogenesis. Overexpression of ribosomal proteins, particularly Rpl15, which gradually increased from the 1-cell to 8-cell stages, indicated persistent hyperactivation of ribosome biogenesis, which promoted tumorigenesis in offspring derived from oxidatively damaged IVF embryos by selectively enhancing the translation of β-Catenin and TGF-β1. The antioxidant epigallocatechin-3-gallate (EGCG) was added to the in vitro culture medium to protect embryos from oxidative damage, and the expression of ribosome-/tumor-related proteins returned to normal after EGCG treatment. This study suggests that regulation of ribosome biogenesis by EGCG may be a means of preventing tumor formation in human IVF-derived offspring, providing a scientific basis for optimizing in vitro culture conditions and improving human-assisted reproductive technology.
Coordination between cell proliferation and apoptosis after DNA damage in Drosophila
Authors: Ruiz-Losada Mireya , González Raul , Peropadre Ana , Gil-Gálvez Alejandro , Tena Juan J. , Baonza Antonio , Estella Carlos 
Published: November 2021

AbstractExposure to genotoxic stress promotes cell cycle arrest and DNA repair or apoptosis. These “life” or “death” cell fate decisions often rely on the activity of the tumor suppressor gene p53. Therefore, the precise regulation of p53 is essential to maintain tissue homeostasis and to prevent cancer development. However, how cell cycle progression has an impact on p53 cell fate decision-making is mostly unknown. In this work, we demonstrate that Drosophila p53 proapoptotic activity can be impacted by the G2/M kinase Cdk1. We find that cell cycle arrested or endocycle-induced cells are refractory to ionizing radiation-induced apoptosis. We show that p53 binding to the regulatory elements of the proapoptotic genes and its ability to activate their expression is compromised in experimentally arrested cells. Our results indicate that p53 genetically and physically interacts with Cdk1 and that p53 proapoptotic role is regulated by the cell cycle status of the cell. We propose a model in which cell cycle progression and p53 proapoptotic activity are molecularly connected to coordinate the appropriate response after DNA damage.
Towards unraveling the moisture-induced shape memory effect of wood: the role of interface mechanics revealed by upscaling atomistic to composite modeling
Authors: Zhang Chi , Chen Mingyang , Keten Sinan , Derome Dominique , Carmeliet Jan 
Published: November 2021

AbstractThe moisture-induced shape memory effect (SME) is one of the most intriguing phenomena of wood, where wood can stably retain a certain deformed shape and, upon moisture sorption, can recover the original shape. Despite the long history of wood utilization, the SME is still not fully understood. Combining molecular dynamics (MD) and finite-element (FE) modeling, a possible mechanism of the SME of wood cell walls is explored, emphasizing the role of interface mechanics, a factor previously overlooked. Interface mechanics extracted from molecular simulations are implemented in different mechanical models solved by FEs, representing three configurations encountered in wood cell walls. These models incorporate moisture-dependent elastic moduli of the matrix and moisture-dependent behavior of the interface. One configuration, denoted as a mechanical hotspot with a fiber–fiber interface, is found to particularly strengthen the SME. Systematic parametric studies reveal that interface mechanics could be the source of shape memory. Notably, upon wetting, the interface is weak and soft, and the material can be easily deformed. Upon drying, the interface becomes strong and stiff, and composite deformation can be locked. When the interface is wetted again and weakened, the previously locked deformation cannot be sustained, and recovery occurs. The elastic energy and topological information stored in the cellulose fiber network is the driving force of the recovery process. This work proposes an interface behaving as a moisture-induced molecular switch.
A polygenic risk score for multiple myeloma risk prediction
Authors: Canzian Federico , Piredda Chiara , Macauda Angelica , Zawirska Daria , Andersen Niels Frost , Nagler Arnon , Zaucha Jan Maciej , Mazur Grzegorz , Dumontet Charles , Wątek Marzena , Jamroziak Krzysztof , Sainz Juan , Várkonyi Judit , Butrym Aleksandra , Beider Katia , Abildgaard Niels , Lesueur Fabienne , Dudziński Marek , Vangsted Annette Juul , Pelosini Matteo , Subocz Edyta , Petrini Mario , Buda Gabriele , Raźny Małgorzata , Gemignani Federica , Marques Herlander , Orciuolo Enrico , Kadar Katalin , Jurczyszyn Artur , Druzd-Sitek Agnieszka , Vogel Ulla , Andersen Vibeke , Reis Rui Manuel , Suska Anna , Avet-Loiseau Hervé , Kruszewski Marcin , Tomczak Waldemar , Rymko Marcin , Minvielle Stephane , Campa Daniele 
Published: November 2021

AbstractThere is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p = 3.55 × 10−15 for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p = 1.62 × 10−13 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.
Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis
Authors: Uriarte Maxime , Sen Nkwe Nadine , Tremblay Roch , Ahmed Oumaima , Messmer Clémence , Mashtalir Nazar , Barbour Haithem , Masclef Louis , Voide Marion , Viallard Claire , Daou Salima , Abdelhadi Djaileb , Ronato Daryl , Paydar Mohammadjavad , Darracq Anaïs , Boulay Karine , Desjardins-Lecavalier Nicolas , Sapieha Przemyslaw , Masson Jean-Yves , Sergeev Mikhail , Kwok Benjamin H. , Hulea Laura , Mallette Frédérick A. , Milot Eric , Larrivée Bruno , Wurtele Hugo , Affar El Bachir 
Published: November 2021

AbstractEukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions.
Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes
Authors: Abascal-Palacios Guillermo , Jochem Laura , Pla-Prats Carlos , Beuron Fabienne , Vannini Alessandro 
Published: November 2021

AbstractRetrotransposons are endogenous elements that have the ability to mobilise their DNA between different locations in the host genome. The Ty3 retrotransposon integrates with an exquisite specificity in a narrow window upstream of RNA Polymerase (Pol) III-transcribed genes, representing a paradigm for harmless targeted integration. Here we present the cryo-EM reconstruction at 4.0 Å of an active Ty3 strand transfer complex bound to TFIIIB transcription factor and a tRNA gene. The structure unravels the molecular mechanisms underlying Ty3 targeting specificity at Pol III-transcribed genes and sheds light into the architecture of retrotransposon machinery during integration. Ty3 intasome contacts a region of TBP, a subunit of TFIIIB, which is blocked by NC2 transcription regulator in RNA Pol II-transcribed genes. A newly-identified chromodomain on Ty3 integrase interacts with TFIIIB and the tRNA gene, defining with extreme precision the integration site position.
3D in vitro M2 macrophage model to mimic modulation of tissue repair
Authors: Sapudom Jiranuwat , Karaman Shaza , Mohamed Walaa K. E. , Garcia-Sabaté Anna , Quartey Brian C. , Teo Jeremy C. M. 
Published: November 2021

AbstractDistinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages, and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our cell characterization suggested that MIL-4/IL-13 and MIL-10 demonstrate M2a- and M2c-like subtypes, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 were able to promote matrix synthesis and remodeling by induction of myofibroblast differentiation via transforming growth factor beta-1 (TGF-β1). On the contrary, MIL-10 demonstrated the ability to resolve the tissue repair process by dedifferentiation of myofibroblast via IL-10 secretion. Overall, our study demonstrated the importance and the exact roles of M2a and M2c-like macrophage subtypes in coordinating tissue repair in a biomimetic model. The established model can be applied for high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.
RETRACTED ARTICLE: Performance of sustainable self-compacting fiber reinforced concrete with substitution of marble waste (MW) and coconut fibers (CFs)
Authors: Ahmad Jawad , Aslam Fahid , Martinez-Garcia Rebeca , Ouni Mohamed Hechmi El , Khedher Khalid Mohamed 
Published: November 2021

AbstractSelf compacting concrete (SCC) is special type of concrete which is highly flowable and non-segregated and by its own mass, spreads into the formwork without any external vibrators, even in the presence of thick reinforcement. But SSC is also brittle nature like conventional concrete, which results in abrupt failure without giving any deformation (warning), which is undesirable for any structural member. Thus, self-compacting concrete (SCC) needs some of tensile reinforcement to enhance tensile strength and prevent the unsuitable abrupt failure. But fiber increased tensile strength of concrete more effectively than compressive strength. Hence, it is essential to add pozzolanic materials into fiber reinforced concrete to achieve high strength, durable and ductile concrete. This study is conducted to assess the performance of SCC with substitutions of marble waste (MW) and coconut fiber (CFs) into SCC. MW utilized as cementitious (pozzolanic) materials in percentage of 5.0 to 30% in increment of 5.0% by weight of binder and concrete is reinforced with CFs in proportion of 0.5 to 3.0% in increment of 0.5% by weight of binder. Rheological characteristics were measured through its filling and passing ability by using Slump flow, Slump T50, L-Box, and V-funnel tests while mechanical characteristics were measured through compressive strength, split tensile strength, flexure strength and bond strength (pull out) tests. Experimental investigation show that MW and CFs decrease the passing ability and filling ability of SCC. Additionally, Experimental investigation show that MW up to 20% and CFs addition 2.0% by weight of binder tend to increase the mechanical performance of SCC. Furthermore, statistical analysis (RSM) was used to optimize the combined dose of MW and CFs into SCC to obtain high strength self-compacting concrete.
A repeated-measures study on emotional responses after a year in the pandemic
Authors: Mozes Maximilian , van der Vegt Isabelle , Kleinberg Bennett 
Published: November 2021

AbstractThe introduction of COVID-19 lockdown measures and an outlook on return to normality are demanding societal changes. Among the most pressing questions is how individuals adjust to the pandemic. This paper examines the emotional responses to the pandemic in a repeated-measures design. Data (n = 1698) were collected in April 2020 (during strict lockdown measures) and in April 2021 (when vaccination programmes gained traction). We asked participants to report their emotions and express these in text data. Statistical tests revealed an average trend towards better adjustment to the pandemic. However, clustering analyses suggested a more complex heterogeneous pattern with a well-coping and a resigning subgroup of participants. Linguistic computational analyses uncovered that topics and n-gram frequencies shifted towards attention to the vaccination programme and away from general worrying. Implications for public mental health efforts in identifying people at heightened risk are discussed. The dataset is made publicly available.
Quantifying the effect of genetic, environmental and individual demographic stochastic variability for population dynamics in Plantago lanceolata
Authors: Steiner Ulrich K. , Tuljapurkar Shripad , Roach Deborah A. 
Published: November 2021

AbstractSimple demographic events, the survival and reproduction of individuals, drive population dynamics. These demographic events are influenced by genetic and environmental parameters, and are the focus of many evolutionary and ecological investigations that aim to predict and understand population change. However, such a focus often neglects the stochastic events that individuals experience throughout their lives. These stochastic events also influence survival and reproduction and thereby evolutionary and ecological dynamics. Here, we illustrate the influence of such non-selective demographic variability on population dynamics using population projection models of an experimental population of Plantago lanceolata. Our analysis shows that the variability in survival and reproduction among individuals is largely due to demographic stochastic variation with only modest effects of differences in environment, genes, and their interaction. Common expectations of population growth, based on expected lifetime reproduction and generation time, can be misleading when demographic stochastic variation is large. Large demographic stochastic variation exhibited within genotypes can lower population growth and slow evolutionary adaptive dynamics. Our results accompany recent investigations that call for more focus on stochastic variation in fitness components, such as survival, reproduction, and functional traits, rather than dismissal of this variation as uninformative noise.
Disparate effects of MMP and TIMP modulation on coronary atherosclerosis and associated myocardial fibrosis
Authors: Kremastiotis Georgios , Handa Ishita , Jackson Christopher , George Sarah , Johnson Jason 
Published: November 2021

AbstractMatrix metalloproteinase (MMP) activity is tightly regulated by the endogenous tissue inhibitors (TIMPs), and dysregulated activity contributes to extracellular matrix remodelling. Accordingly, MMP/TIMP balance is associated with atherosclerotic plaque progression and instability, alongside adverse post-infarction cardiac fibrosis and subsequent heart failure. Here, we demonstrate that prolonged high-fat feeding of apolipoprotein (Apo)e-deficient mice triggered the development of unstable coronary artery atherosclerosis alongside evidence of myocardial infarction and progressive sudden death. Accordingly, the contribution of select MMPs and TIMPs to the progression of both interrelated pathologies was examined in Apoe-deficient mice with concomitant deletion of Mmp7, Mmp9, Mmp12, or Timp1 and relevant wild-type controls after 36-weeks high-fat feeding. Mmp7 deficiency increased incidence of sudden death, while Mmp12 deficiency promoted survival, whereas Mmp9 or Timp1 deficiency had no effect. While all mice harboured coronary disease, atherosclerotic burden was reduced in Mmp7-deficient and Mmp12-deficient mice and increased in Timp1-deficient animals, compared to relevant controls. Significant differences in cardiac fibrosis were only observed in Mmp-7-deficient mice and Timp1-deficient animals, which was associated with reduced capillary number. Adopting therapeutic strategies in Apoe-deficient mice, TIMP-2 adenoviral-overexpression or administration (delayed or throughout) of a non-selective MMP inhibitor (RS-130830) had no effect on coronary atherosclerotic burden or cardiac fibrosis. Taken together, our findings emphasise the divergent roles of MMPs on coronary plaque progression and associated post-MI cardiac fibrosis, highlighting the need for selective therapeutic approaches to target unstable atherosclerosis alongside adverse cardiac remodelling while negating detrimental adverse effects on either pathology, with targeting of MMP-12 seeming a suitable target.