bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread regulatory specificities between transcriptional corepressors and enhancers inDrosophila
Authors: Jacobs Jelle , Pagani Michaela , Wenzl Christoph , Stark Alexander 
Published: November 2022

AbstractAnimal development and homeostasis critically depend on the accurate regulation of gene transcription, which includes the silencing of genes that should not be expressed. Repression is mediated by a specific class of transcription factors (TFs) termed repressors that, via the recruitment of co-repressors (CoRs), can dominantly prevent transcription, even in the presence of activating cues. However, the relationship between specific CoRs and enhancers has remained unclear. Here, we used functional genomics to uncover regulatory specificities between CoRs and enhancers. We show that enhancers can typically be repressed by only a subset of CoRs. Enhancers classified by CoR sensitivity also show distinct biological functions and endogenous chromatin features. Moreover, enhancers that are sensitive or resistant to silencing by specific CoRs differ in TF motif content, and their sensitivity to CoRs can be predicted based on TF motif content. Finally, we identified and validated specific TF motifs that have a direct impact on enhancers sensitivity or resistance towards specific CoRs, using large scale motif mutagenesis and addition experiments.This study reveals the existence of TF motif-based regulatory rules that coordinate CoRs-enhancer compatibilities. These specificities between repressors and activators not only suggest that repression occurs via distinct mechanisms, but also provide an additional layer in transcriptional regulation that allows for differential repression at close genomic distances and offers multiple ways for de-repression.
Optimization of modularity during development to simplify walking control across strides
Authors: Hinnekens Elodie , Berret Bastien , Morard Estelle , Do Manh-Cuong , Barbu-Roth Marianne , Teulier Caroline 
Published: November 2022

AbstractWalking in adults seems to rely on a small number of modules allowing to reduce the number of degrees of freedom effectively regulated by the central nervous system (CNS). However, the extent to which modularity evolves during development remains unknown, particularly regarding the ability to generate several strides in an optimized manner. Here we compared the modular organization of toddlers and adults during several strides of walking. We recorded the electromyographic activity of 10 bilateral (lower limbs) muscles in adults (n=12) and toddlers (n=12) during 8 gait cycles, and used non-negative matrix factorization to model the underlying modular command. While the muscular activity of all strides could be factorized into a consistent low-dimensional modular organization in adults, significantly more computational modules were needed in toddlers to account for their greater stride-by-stride variability. Activations of these modules varied more across strides and was less parsimonious in toddlers than in adults, even when balances constrained were diminished. These findings suggest that the modular control of locomotion of adults evolves as the organism develops and practices. They also suggest that new walker can flexibly activate a higher number of modules and benefit from a higher space of possible action, which could serve motor exploration.
DNA origami directed virus capsid polymorphism
Authors: Seitz Iris , Kumpula Esa-Pekka , Anaya-Plaza Eduardo , Cornelissen Jeroen J. L. M. , Linko Veikko , Huiskonen Juha T. , Kostiainen Mauri A. 
Published: November 2022

AbstractMost known viruses protect their genome by encapsulating it inside a protein capsid. Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. The assembly process of native capsids is highly cooperative and governed by the protein geometry, protein-protein as well as protein-nucleic acid interactions. Importantly, the absolute control over the size and shape of virus capsids would have imminent advantages in the development of new vaccines and delivery systems. However, tools to direct the assembly process in a programmable manner are exceedingly elusive or strictly limited to specific structures. Here, we introduce a modular approach by demonstrating DNA origami directed polymorphism of single protein subunit capsids. We achieve control over the capsid shape, size, and topology by employing user-defined DNA origami nanostructures as binding and assembly platforms for the capsid proteins. Binding assays and single-particle cryo-electron microscopy reconstruction show that the DNA origami nanoshapes are efficiently encapsulated within the capsid. Further, we observe that helical arrangement of hexameric capsomers is the preferred mode of packing, while a negative curvature of the origami structure is not well tolerated. The capsid proteins assemble on DNA origami in single or double layer configurations depending on the applied stoichiometry. In addition, the obtained viral capsid coatings are able to efficiently shield the encapsulated DNA origami from nuclease degradation and prevent the structures from aggregation. Therefore, these findings may in addition find direct implementations in DNA nanotechnology-based bioengineering by paving the way for the next-generation cargo protection and targeting strategies.
Rescue of the increased susceptibility to Mild Chronic Oxidative Stress of iNeurons carrying the MAPT Chromosome 17q21.3 H1/H1 risk allele by FDA-approved compounds
Authors: Sadikoglou E , Domingo-Fernández D , Savytska N , Fernandes N , Rizzu P , Illarionova A , Strauß T , Schwarz SC , Kodamullil A , Höglinger GU , Dhingra A , Heutink P 
Published: November 2022

AbstractThe microtubule associated protein tau (MAPT) chromosome 17q21.31 locus lies within a region of high linkage disequilibrium (LD) conferring two extended haplotypes commonly referred to as H1 and H2. The major haplotype, H1 has been genetically associated with an increased risk for multiple neurodegenerative disorders, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD),APOEε4-negative Alzheimer’s disease (AD) and Parkinson’s disease (PD). The mechanism causing this increased risk is largely unknown. Here, we investigated the role of Mild Chronic Oxidative Stress (MCOS) in neurogenin 2 (NGN2) induced neurons (iNeurons) derived from iPS (induced pluripotent stem cells) from carriers of both haplotypes. We identified that iNeurons of the H1 homozygous haplotype showed an increased susceptibility to MCOS compared to homozygous H2 carriers, leading to cell death through ferroptosis. We performed a cellular screen in H1 iNeurons using a FDA-approved Drug Library and identified candidate molecules that rescued the increased susceptibility to MCOS and prevented ferroptosis in H1 iNeurons.HighlightsMild Chronic Oxidative Stress induces neurotoxicity via ferroptosis on iNGN2 neuronsAxonal degeneration, disordered microtubules, blebs precede neurotoxicityMAPT-17q21.3 locus H1/H1, risk allele for NDD is more vulnerable to MCOSFDA-approved drugs reverse MCOS induced ferroptosis on H1/H1 risk alleleAbstract Figure
Cryo-EM Structures of Amyloid-β Filaments With the Arctic Mutation (E22G) From Human and Mouse Brains
Authors: Yang Yang , Zhang Wenjuan , Murzin Alexey G. , Schweighauser Manuel , Huang Melissa , Lövestam Sofia , Peak-Chew Sew Y. , Saito Takashi , Saido Takaomi C. , Macdonald Jennifer , Lavenir Isabelle , Ghetti Bernardino , Graff Caroline , Kumar Amit , Nordberg Agneta , Goedert Michel , Scheres Sjors H.W. 
Published: November 2022

ABSTRACTThe Arctic mutation, encoding E693G in theamyloid precursor protein (APP)gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer’s disease. Here we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case (AβPParc1) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12-V40 (human Arctic fold A) and E11-G37 (human Arctic fold B). They have a substructure (residues F20-G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in lineAppNL-G-F. Most filaments are made of two identical mutant protofilaments that extend from D1-G37 (murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The murine Arctic fold differs from the human Arctic folds, but shares some substructure.
Molecular characterization of a DyP-type peroxidase from the human parasitic cestodeEchinococcus multilocularis
Authors: Ulrich Johannes , Brehm Klaus 
Published: November 2022

AbstractThe lethal zoonosis alveolar echinococcosis is caused by the metacestode larval stage of the tapewormEchinococcus multilocularis. During the chronic phase of the disease, metacestode tissue is growing infiltratively into liver tissue and provokes an immunes response of the host. Mechanisms of parasite defence against reactive oxygen species (ROS), which are produced during parasite growth and host immune responses, are incompletely understood so far. We herein describe the characterization of anEchinococcusDyp (dye decolorizing) – type peroxidase, EmDyp, family members of which are typically expressed by bacteria and fungi. EmDyp showed significant homologies to bacterial and fungal Dyp peroxidases and recombinantly expressed EmDyp displayed profound enzymatic activity towards different substrates such as 3,3’-diaminobenzidine or luminol. Furthermore, although structurally not being related to classical catalases, EmDyp showed catalase activity in respective activity gels.In situhybridization experiments showed expression of the EmDyp expressing gene,emdyp, in the germinal layer of the metacestode as well as in the posterior region of the protoscolex, both in differentiated and in germinative (stem) cells of the parasite. Interestingly, RT-qPCR experiments demonstrated thatemdypexpression is induced in the metacestode upon growth under aerobic conditions. Particularly high expression ofemdypwas observed underin vivogrowth conditions in jirds within the liver. These data indicate a role of EmDyp in the defence of the metacestode against host- and/or parasite-derived ROS during chronic alveolar echinococcosis. Since Dyp-type peroxidases are not encoded on the genomes of mammalian hosts forE. multilocularis, EmDyp might be used as a target molecule for developing novel therapeutics against the parasite.
New Zealand: Political Developments and Data in 2021
Authors: BARKER FIONA 
Published: November 2022

AbstractAfter the successful adoption of a COVID‐19 elimination strategy in 2020, in 2021 the New Zealand government introduced strategies to limit and mitigate the spread of the virus, as the elimination strategy looked increasingly unsustainable. It rolled out vaccines, imposed vaccine mandates and grappled with the complexities of the largely closed border. Despite the continuing pandemic demands, the Labour government, now with an outright majority after the General Election in late 2020, attempted to make progress on elements of its reform agenda in health, housing, water, transport and some social areas. Opposition to these reforms, which had a centralizing thrust and expanded in limited ways the scope of Māori participation in governance and decision‐making, was swift. By the end of the year, emerging debates about vaccine mandates and public weariness with lockdowns contributed to growing discontent with the government's COVID‐19 policies.
Triangulation of evidence on immigration and rates of alcohol use disorder in Sweden: Evidence of acculturation effects
Authors: Chartier Karen G. , Kendler Kenneth S. , Ohlsson Henrik , Sundquist Kristina , Sundquist Jan 
Published: November 2022

AbstractBackgroundThis study aimed to determine the robustness of the impact of immigration on risk for alcohol use disorder (AUD) using different measures, designs, and immigrant regional cohorts.MethodsThe analytic sample included all individuals born between 1950 and 1990 and registered in Sweden from 1973 to 2017. Using Cox regression models, we examined the risk for AUD from Swedish nationwide registries in immigrants to Sweden from seven geographical regions: Africa, Asia and Oceania, Eastern Europe, Finland, Latin America and the Caribbean, Middle East/North Africa, and Western countries. We assessed greater exposure to Swedish culture, which we interpreted as increasing acculturation, by (i) comparing first‐generation immigrants and their children with no and one native Swedish parent and (ii) examining age at immigration. The baseline comparison group was the native Swedish population. We also examined AUD risk in first‐generation sibling pairs discordant for their age at immigration.ResultsIn nearly all immigrant cohorts in Sweden, increasing degrees of acculturation, as assessed by both our variables, were associated with rates of AUD that approached those of the Swedish population. These findings occurred in both men and women and both regional cohorts whose first‐generation immigrants had lower and higher levels of AUD than native‐born Swedes. For most cohorts, the rates of change with acculturation were greater in women than in men. In sibling pairs from most regions, the sibling who was younger at immigration had a higher rate of AUD.ConclusionsAn examination of both sexes and two different proxies for acculturation provides consistent support for socio‐cultural influences on AUD risk. Our co‐sibling analyses suggest that a meaningful proportion of this effect is likely to be causal in nature.
The rise of robots and the fall of cost stickiness: Evidence from Chinese manufacturers
Authors: Jia Wanjiao , Yang Ting , Zhang Xin 
Published: November 2022

AbstractIndustrial robots are increasingly used to perform tasks traditionally assigned to humans. Using a sample of Chinese manufacturers, we examine the impact of robot adoption on firm cost stickiness. We find that robot adoption is associated with less sticky costs. The negative impact of robot adoption on cost stickiness is particularly meaningful for state‐owned enterprises and firms with higher labour costs, and becomes significantly stronger after the enactment of China's Labour Contract Law, which significantly increases labour adjustment costs. These findings are consistent with the conjecture that the adoption of robots allows firms to reduce their overall labour adjustment costs.
Influencing factors of meaning in life in patients with advanced lung cancer undergoing radiochemotherapy: A cross‐sectional survey
Authors: Li Yumei , Zhang Meirong , Yang Chunhong , Luo Yifan 
Published: November 2022

AbstractAimTo examine the factors that influence meaning in life (MiL) in patients with advanced lung cancer who are undergoing radiochemotherapy.MethodsA cross‐sectional, multivariate stepwise regression analysis and structural equation modeling were used to examine factors influencing MiL in 231 patients with lung cancer in an oncology department of a tertiary hospital in China. Their mood state, family care, social support, and psychological distress were measured.ResultsSex, marital status, and family income significantly affected MiL (p < .05). MiL was significantly correlated (p < .01) with psychological distress (r = −.203), and most significantly (F = 66.883, p < .01; 46.2% of MiL) with mood state (r = −.631), family care (r = .384), and social support (r = .410).ConclusionTo enhance MiL, nurses need to consider patients’ mood states and family/social support, as well as tailor patient care toward different sexes and backgrounds. Clinical staff should pay attention to the psychological changes, family care, and social support of patients with advanced lung cancer.
The analysis of two historic fired artificial stonewares: Coade stone (18th–19th centuries) and a recent discovery from Oxnead Hall, Norfolk (16th–17th centuries)
Authors: Brooke Christopher J. , Edwards Howell G. M. , Košek Filip , Jehlička Jan , Stanford Caroline , Champion Matthew J. 
Published: November 2022

AbstractCoade stone has played a significant role in architectural and ornamental design since its inception in the early 18th century. It is well known that earlier, experimental, architectural stoneware products existed, but few of these have been studied in detail scientifically, and only one major analytical study of Coade stone has appeared in the literature. This paper presents a new spectroscopic analysis of Coade stone along with that of a newly discovered sample from Oxnead Hall in Norfolk where it known that Sir Clement Paston experimented with artificial stone in the late 16th century. The results demonstrate that it is possible to differentiate between the two variants on the basis of both the raw materials used and the different phases formed in their production processes.
Rare case of a right Bochdalek hernia with retroperitoneal prolapse of organs into the thoracic cavity in infancy: A case report
Authors: Nakagawa Yoichi , Uchida Hiroo , Hinoki Akinari , Shirota Chiyoe , Sumida Wataru , Makita Satoshi , Amano Hizuru , Masamune Okamoto , Takimoto Aitaro , Ogata Seiya , Takada Shunya , Kato Daiki , Gohda Yousuke , Guo Yaohui 
Published: November 2022

AbstractWe report an extremely rare case of a right Bochdalek hernia with a sac, in which the retroperitoneal and intra‐abdominal organs prolapsed into the thoracic cavity at the same time. The patient was a 7‐month‐old female with no comorbidities. She presented with cough and fever, and chest radiography revealed a right diaphragmatic hernia. Computed tomography showed that the right kidney, intestine, colon, and liver had prolapsed into the thoracic cavity. The patient underwent thoracoscopic surgery, which showed that the abdominal and retroperitoneal organs prolapsed into the thoracic cavity through the Bochdalek hernia. The herniated organs were spontaneously reduced using thoracoscopic insufflation. The defect hole was closed with artificial mesh. We adopted a thoracoscopic approach, in terms of easy reduction of herniated organs and accurate evaluation of the hernia orifice, which was useful.
La Théorie Critique De La Race, Un Outil De Lecture Des Relations Ambiguës Entre Les Communautés Francophones En Situation Minoritaire Et Leurs Immigrants Noirs Francophones
Authors: Sall Leyla , Zellama Faiçal , Piquemal Nathalie , Huot Suzanne 
Published: November 2022

AbstractIn becoming host communities for Francophone immigrants in the early 2000s, Canada's Francophone minority communities (FMCs) are facing the test of moving away from a predominant ethnic nationalism to an inclusive civic nationalism. The reception and integration of Black and Francophone immigrants is therefore a relevant indicator of the success of this test. Drawing on critical race theory and bricolage methodology, we reconstruct the ambiguous relationship between FMCs and their Black francophone immigrants who are both invited into French society and discriminated against.
Corticosteroid nasal irrigation as early treatment of olfactory dysfunction in COVID‐19: A prospective randomised controlled trial
Authors: Tragoonrungsea Jidapa , Tangbumrungtham Navarat , Nitivanichsakul Tuleeya , Roongpuvapaht Boonsam , Tanjararak Kangsadarn 
Published: November 2022

AbstractObjectiveThis study aimed to evaluate the efficacy of corticosteroid irrigation compared to saline to no nasal irrigation in COVID‐19 patients with olfactory loss.Design and SettingA randomised controlled study was conducted at the Otolaryngology‐Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University.ParticipantsTwo hundred thirty‐seven COVID‐19 participants with a new‐onset smell loss were recruited into the study. Two hundred twenty‐two participants met the inclusion criteria and were randomised into three groups: corticosteroid irrigation, saline irrigation and no treatment.Main Outcome MeasuresThe primary outcome was the mean difference in the smell sensation score among the groups after treatment at 1, 2 and 6 weeks. The secondary outcomes measurements included (1) a self‐rating quality of life (QOL)‐related smell dysfunction score, (2) the change over time in smell sensation score and self‐rating QOL‐related smell dysfunction score and (3) the median time to complete recovery of smell loss.ResultsThe mean differences in smell sensation scores among the three groups were not statistically significant at any follow‐up period. The mean score of self‐rating QOL‐related smell dysfunction in the corticosteroid group was significantly better than the other groups at 1 week. The change of outcome scores showed significant improvement over time, regardless of the treatments. The median time to complete smell recovery was similar: 3 weeks.ConclusionThis study emphasised that corticosteroid nasal irrigation is not superior to saline or no nasal irrigation in restoring the sense of smell in COVID‐19‐associated olfactory loss.
Hierarchical Dirichlet and Pitman–Yor process mixtures of shifted‐scaled Dirichlet distributions for proportional data modeling
Authors: Baghdadi Ali , Manouchehri Narges , Patterson Zachary , Fan Wentao , Bouguila Nizar 
Published: November 2022

AbstractIn this article, first, we propose a novel unsupervised learning method based on a hierarchical Dirichlet process mixture of shifted‐scaled Dirichlet (SSD) distributions. Second, we extend it to a hierarchical Pitman–Yor process mixture of SSD distributions. The goal is to find a model that properly fits complex real‐world data. Our models are based on SSD distributions that are more flexible than Dirichlet distribution in fitting proportional data. Simultaneous data fitting (parameter estimate) and model selection (model complexity determination) are possible with the suggested methods. We applied batch and online variational inference for learning the models. The online setting allows us to feed our models with large‐scale streaming data. The effectiveness of our proposed models is evaluated by four realistic and challenging applications, namely, spam email detection, texture clustering, traffic sign detection, and vehicle detection. Experimental results demonstrate the potential of our models to fit proportional data.