bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG
Authors: Ali Aamir , Vineethakumari Chithran , Lacasa Cristina , Lüders Jens 
Published: January 2023

AbstractOrganization of microtubule arrays requires spatio-temporal regulation of the microtubule nucleator γ-tubulin ring complex (γTuRC) at microtubule organizing centers (MTOCs). MTOC-localized adapter proteins are thought to recruit and activate γTuRC, but the molecular underpinnings remain obscure. Here we show that at interphase centrosomes, rather than adapters, the microtubule polymerase ch-TOG (also named chTOG or CKAP5) ultimately controls γTuRC recruitment and activation. ch-TOG co-assembles with γTuRC to stimulate nucleation around centrioles. In the absence of ch-TOG, γTuRC fails to localize to these sites, but not the centriole lumen. However, whereas some ch-TOG is stably bound at subdistal appendages, it only transiently associates with PCM. ch-TOG’s dynamic behavior requires its tubulin-binding TOG domains and a C-terminal region involved in localization. In addition, ch-TOG also promotes nucleation from the Golgi. Thus, at interphase centrosomes stimulation of nucleation and γTuRC attachment are mechanistically coupled through transient recruitment of ch-TOG, and ch-TOG’s nucleation-promoting activity is not restricted to centrosomes.
TadA reprogramming to generate potent miniature base editors with high precision
Authors: Zhang Shuqian , Song Liting , Yuan Bo , Zhang Cheng , Cao Jixin , Chen Jinlong , Qiu Jiayi , Tai Yilin , Chen Jingqi , Qiu Zilong , Zhao Xing-Ming , Cheng Tian-Lin 
Published: January 2023

AbstractAlthough miniature CRISPR-Cas12f systems were recently developed, the editing efficacy and targeting range of derived miniature cytosine and adenine base editors (miniCBEs and miniABEs) have not been comprehensively addressed. Moreover, functional miniCBEs have not yet be established. Here we generate various Cas12f-derived miniCBEs and miniABEs with improved editing activities and diversified targeting scopes. We reveal that miniCBEs generated with traditional cytidine deaminases exhibit wide editing windows and high off-targeting effects. To improve the editing signatures of classical CBEs and derived miniCBEs, we engineer TadA deaminase with mutagenesis screening to generate potent miniCBEs with high precision and minimized off-target effects. We show that newly designed miniCBEs and miniABEs are able to correct pathogenic mutations in cell lines and introduce genetic mutations efficiently via adeno-associated virus delivery in the brain in vivo. Together, this study provides alternative strategies for CBE development, expands the toolkits of miniCBEs and miniABEs and offers promising therapeutic tools for clinical applications.
Biomolecular condensates formed by designer minimalistic peptides
Authors: Baruch Leshem Avigail , Sloan-Dennison Sian , Massarano Tlalit , Ben-David Shavit , Graham Duncan , Faulds Karen , Gottlieb Hugo E. , Chill Jordan H. , Lampel Ayala 
Published: January 2023

AbstractInspired by the role of intracellular liquid-liquid phase separation (LLPS) in formation of membraneless organelles, there is great interest in developing dynamic compartments formed by LLPS of intrinsically disordered proteins (IDPs) or short peptides. However, the molecular mechanisms underlying the formation of biomolecular condensates have not been fully elucidated, rendering on-demand design of synthetic condensates with tailored physico-chemical functionalities a significant challenge. To address this need, here we design a library of LLPS-promoting peptide building blocks composed of various assembly domains. We show that the LLPS propensity, dynamics, and encapsulation efficiency of compartments can be tuned by changes to the peptide composition. Specifically, with the aid of Raman and NMR spectroscopy, we show that interactions between arginine and aromatic amino acids underlie droplet formation, and that both intra- and intermolecular interactions dictate droplet dynamics. The resulting sequence-structure-function correlation could support the future development of compartments for a variety of applications.
Variable temperature thresholds of melt pond formation on Antarctic ice shelves
Authors: van Wessem J. Melchior , van den Broeke Michiel R. , Wouters Bert , Lhermitte Stef 
Published: January 2023

AbstractIt has been argued that the −5 °C annual mean 2 m air temperature isotherm defines a limit of ice shelf viability on the Antarctic Peninsula as melt ponding increases at higher temperatures. It is, however, presently unknown whether this threshold can also be applied to other Antarctic ice shelves. Here we use two present-day and three future high-resolution Antarctic climate simulations to predict warming thresholds for Antarctic ice shelf melt pond formation on the basis of the melt-over-accumulation ratio. The associated warming thresholds match well with observed melt pond volumes and are found to be spatially highly variable and controlled by snow accumulation. For relatively wet ice shelves, the −5 °C temperature threshold was confirmed; but cold and dry ice shelves such as Amery, Ross and Filchner-Ronne are more vulnerable than previously thought, with threshold temperatures well below −15 °C. Coupled Model Intercomparison Project Phase 6 models predict that towards the end of this century these thresholds can be reached on many ice shelves, even on cold ice shelves and under moderate warming scenarios.
Genetic assimilation of ancestral plasticity during parallel adaptation to zinc contamination in Silene uniflora
Authors: Wood Daniel P. , Holmberg Jon A. , Osborne Owen G. , Helmstetter Andrew J. , Dunning Luke T. , Ellison Amy R. , Smith Rhian J. , Lighten Jackie , Papadopulos Alexander S. T. 
Published: January 2023

AbstractPhenotypic plasticity in ancestral populations is hypothesized to facilitate adaptation, but evidence is piecemeal and often contradictory. Further, whether ancestral plasticity increases the probability of parallel adaptive changes has not been explored. The most general finding is that ancestral responses to a new environment are reversed following adaptation (known as reversion). We investigated the contribution of ancestral plasticity to adaptive evolution of gene expression in two independently evolved lineages of zinc-tolerant Silene uniflora. We found that the general pattern of reversion is driven by the absence of a widespread stress response in zinc-adapted plants compared with zinc-sensitive plants. We show that ancestral plasticity that moves expression closer to the optimum value in the new environment influences the evolution of gene expression among genes that are likely to be involved in adaptation and increases the chance that genes are recruited repeatedly during adaptation. However, despite convergence in gene expression levels between independently adapted lineages, ancestral plasticity does not influence how similar expression values of adaptive genes become. Surprisingly, we also observed that ancestral plasticity that increases fitness often becomes genetically determined and fixed, that is, genetically assimilated. These results emphasize the important role of ancestral plasticity in parallel adaptation.
Evidence for lunar tide effects in Earth’s plasmasphere
Authors: Xiao Chao , He Fei , Shi Quanqi , Liu Wenlong , Tian Anmin , Guo Ruilong , Yue Chao , Zhou Xuzhi , Wei Yong , Rae I. Jonathan , Degeling Alexander W. , Angelopoulos Vassilis , Masongsong Emmanuel V. , Liu Ji , Zong Qiugang , Fu Suiyan , Pu Zuyin , Zhang Xiaoxin , Wang Tieyan , Wang Huizi , Zhang Zhao 
Published: January 2023

AbstractTides are universal and affect spatially distributed systems, ranging from planetary to galactic scales. In the Earth–Moon system, effects caused by lunar tides were reported in the Earth’s crust, oceans, neutral gas-dominated atmosphere (including the ionosphere) and near-ground geomagnetic field. However, whether a lunar tide effect exists in the plasma-dominated regions has not been explored yet. Here we show evidence of a lunar tide-induced signal in the plasmasphere, the inner region of the magnetosphere, which is filled with cold plasma. We obtain these results by analysing variations in the plasmasphere’s boundary location over the past four decades from multisatellite observations. The signal possesses distinct diurnal (and monthly) periodicities, which are different from the semidiurnal (and semimonthly) variations dominant in the previously observed lunar tide effects in other regions. These results demonstrate the importance of lunar tidal effects in plasma-dominated regions, influencing understanding of the coupling between the Moon, atmosphere and magnetosphere system through gravity and electromagnetic forces. Furthermore, these findings may have implications for tidal interactions in other two-body celestial systems.
In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice
Authors: Bouffi Carine , Wikenheiser-Brokamp Kathryn A. , Chaturvedi Praneet , Sundaram Nambirajan , Goddard Gillian R. , Wunderlich Mark , Brown Nicole E. , Staab Janet F. , Latanich Rachel , Zachos Nicholas C. , Holloway Emily M. , Mahe Maxime M. , Poling Holly M. , Vales Simon , Fisher Garrett W. , Spence Jason R. , Mulloy James C. , Zorn Aaron M. , Wells James M. , Helmrath Michael A. 
Published: January 2023

AbstractHuman intestinal organoids (HIOs) derived from pluripotent stem cells provide a valuable model for investigating human intestinal organogenesis and physiology, but they lack the immune components required to fully recapitulate the complexity of human intestinal biology and diseases. To address this issue and to begin to decipher human intestinal–immune crosstalk during development, we generated HIOs containing immune cells by transplanting HIOs under the kidney capsule of mice with a humanized immune system. We found that human immune cells temporally migrate to the mucosa and form cellular aggregates that resemble human intestinal lymphoid follicles. Moreover, after microbial exposure, epithelial microfold cells are increased in number, leading to immune cell activation determined by the secretion of IgA antibodies in the HIO lumen. This in vivo HIO system with human immune cells provides a framework for future studies on infection- or allergen-driven intestinal diseases.
Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25–Nrf2 pathway
Authors: Tanaka Tatsuhide , Okuda Hiroaki , Isonishi Ayami , Terada Yuki , Kitabatake Masahiro , Shinjo Takeaki , Nishimura Kazuya , Takemura Shoko , Furue Hidemasa , Ito Toshihiro , Tatsumi Kouko , Wanaka Akio 
Published: January 2023

AbstractCross-talk between peripheral neurons and immune cells is important in pain sensation. We identifiedSnx25as a pain-modulating gene in a transgenic mouse line with reduced pain sensitivity. Conditional deletion ofSnx25in monocytes and macrophages, but not in peripheral sensory neurons, in mice (Snx25cKOmice) reduced pain responses in both normal and neuropathic conditions. Bone marrow transplantation usingSnx25cKOand wild-type mice indicated that macrophages modulated pain sensitivity. Expression of sorting nexin (SNX)25 in dermal macrophages enhanced expression of the neurotrophic factor NGF through the inhibition of ubiquitin-mediated degradation of Nrf2, a transcription factor that activates transcription ofNgf. As such, dermal macrophages set the threshold for pain sensitivity through the production and secretion of NGF into the dermis, and they may cooperate with dorsal root ganglion macrophages in pain perception.
Persistent mutation burden drives sustained anti-tumor immune responses
Authors: Niknafs Noushin , Balan Archana , Cherry Christopher , Hummelink Karlijn , Monkhorst Kim , Shao Xiaoshan M. , Belcaid Zineb , Marrone Kristen A. , Murray Joseph , Smith Kellie N. , Levy Benjamin , Feliciano Josephine , Hann Christine L. , Lam Vincent , Pardoll Drew M. , Karchin Rachel , Seiwert Tanguy Y. , Brahmer Julie R. , Forde Patrick M. , Velculescu Victor E. , Anagnostou Valsamo 
Published: January 2023

AbstractTumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss in a pan-cancer analysis across 31 tumor types (n = 9,242) and eight immunotherapy-treated cohorts of patients with non-small-cell lung cancer, melanoma, mesothelioma, and head and neck cancer (n = 524). We discovered that mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) which is linked with therapeutic response to immune checkpoint blockade. Persistent mutations were retained in the context of tumor evolution under selective pressure of immunotherapy and tumors with a high pTMB content were characterized by a more inflamed tumor microenvironment. pTMB imposes an evolutionary bottleneck that cancer cells cannot overcome and may thus drive sustained immunologic tumor control in the context of immunotherapy.
A large dataset of scientific text reuse in Open-Access publications
Authors: Gienapp Lukas , Kircheis Wolfgang , Sievers Bjarne , Stein Benno , Potthast Martin 
Published: January 2023

AbstractWe present the Webis-STEREO-21 dataset, a massive collection of Scientific Text Reuse in Open-access publications. It contains 91 million cases of reused text passages found in 4.2 million unique open-access publications. Cases range from overlap of as few as eight words to near-duplicate publications and include a variety of reuse types, ranging from boilerplate text to verbatim copying to quotations and paraphrases. Featuring a high coverage of scientific disciplines and varieties of reuse, as well as comprehensive metadata to contextualize each case, our dataset addresses the most salient shortcomings of previous ones on scientific writing. The Webis-STEREO-21 does not indicate if a reuse case is legitimate or not, as its focus is on the general study of text reuse in science, which is legitimate in the vast majority of cases. It allows for tackling a wide range of research questions from different scientific backgrounds, facilitating both qualitative and quantitative analysis of the phenomenon as well as a first-time grounding on the base rate of text reuse in scientific publications.
Metabolic profiles and fingerprints for the investigation of the influence of nitisinone on the metabolism of the yeast Saccharomyces cerevisiae
Authors: Barchanska Hanna , Płonka Joanna , Nowak Paulina , Kostina-Bednarz Marianna 
Published: January 2023

AbstractNitisinone (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, NTBC) is considered a potentially effective drug for the treatment of various metabolic diseases associated with disorders of l-tyrosine metabolism however, side-effects impede its widespread use. This work aimed to broaden the knowledge of the influence of NTBC and its metabolites 2-amino-4-(trifluoromethyl)benzoic acid (ATFA), 2-nitro-4-(trifluoromethyl)benzoic acid (NTFA), and cyclohexane-1,3-dione (CHD) on the catabolism of l-tyrosine and other endogenous compounds in Saccharomyces cerevisiae. Based on a targeted analysis performed by LC–ESI–MS/MS, based on multiple reaction monitoring, it was found that the dissipation kinetics of the parent compound and its metabolites are compatible with a first-order reaction mechanism. Moreover, it has been proven that formed NTBC metabolites, such as CHD, cause a decrease in l-tyrosine, l-tryptophan, and l-phenylalanine concentrations by about 34%, 59% and 51%, respectively, compared to the untreated model organism. The overall changes in the metabolism of yeast exposed to NTBC or its derivatives were evaluated by non-targeted analysis via LC–ESI–MS/MS in the ion trap scanning mode. Based on principal components analysis, a statistically significant similarity between metabolic responses of yeast treated with ATFA or NTFA was observed. These findings facilitate further studies investigating the influence of NTBC on the human body and the mechanism of its action.
Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
Authors: Spoutil Frantisek , Aranaz-Novaliches Goretti , Prochazkova Michaela , Wald Tomas , Novosadova Vendula , Kasparek Petr , Osicka Radim , Reseland Janne E. , Lyngstadaas Staale P. , Tiainen Hanna , Bousova Kristyna , Vondrasek Jiri , Sedlacek Radislav , Prochazka Jan 
Published: January 2023

AbstractHighly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.
Genetic determinants and absence of breast cancer in Xavante Indians in Sangradouro Reserve, Brazil
Authors: Zhou Yan , Russo Jose , Rueff José , Pires Marcelo A. M. , de Castro Guilherme Bezerra 
Published: January 2023

AbstractGenetic compositions of distinct human populations are different. How genomic variants influence many common and rare genetic diseases is always of great medical and anthropological interest, and understanding of genetic architectures of population groups in relation to diseases can advance our knowledge of medicine. Here, we have studied the genomic architecture of a group of Xavante Indians, an indigenous population in Brazil, and compared them with normal populations from the 1000 Genomes Projects. Principal component analysis (PCA) indicates that the Xavante Indians are genetically distinctive when compared to other ethnic groups. No incidence of breast cancer cases has ever been reported in the population, and polygenic risk analysis indicates extremely low breast cancer risk in this population when compared with germline TCGA (The Cancer Genome Atlas) breast cancer normal control samples. Low germinal mutation burden among this population is also observed. Our findings will help to deepen the understanding of breast cancer and might also provide new approaches to study the disease.
In situ diffraction monitoring of nanocrystals structure evolving during catalytic reaction at their surface
Authors: Zieliński Maciej , Kaszkur Zbigniew , Juszczyk Wojciech , Sobczak Janusz 
Published: January 2023

AbstractWith decreasing size of crystals the number of their surface atoms becomes comparable to the number of bulk atoms and their powder diffraction pattern becomes sensitive to a changing surface structure. On the example of nanocrystalline gold supported on also nanocrystalline $${\text{CeO}}_2$$

CeO
2

we show evolution of (a) the background pattern due to chemisorption phenomena, (b) peak positions due to adsorption on nonstoichiometric $${\text{CeO}}_{2-x}$$

CeO

2
-
x

particles, (c) Au peaks intensity. The results of the measurements, complemented with mass spectrometry gas analysis, point to (1) a multiply twinned structure of gold, (2) high mobility of Au atoms enabling transport phenomena of Au atoms to the surface of ceria while varying the amount of Au in the crystalline form, and (3) reversible $${\text{CeO}}_2$$

CeO
2

peaks position shifts on exposure to He–X–He where X is O2, H2, CO or CO oxidation reaction mixture, suggesting solely internal alternations of the $${\text{CeO}}_2$$

CeO
2

crystal structure. We found no evidence of ceria lattice oxygen being consumed/supplied at any stage of the process. The work shows possibility of structurally interpreting different contributions to the multi-phase powder diffraction pattern during a complex physico-chemical process, including effects of physi-, chemisorption and surface evolution. It shows a way to structurally interpret heterogeneous catalytic reactions even if no bulk phase transition is involved.
Deep-learning-based precise characterization of microwave transistors using fully-automated regression surrogates
Authors: Calik Nurullah , Güneş Filiz , Koziel Slawomir , Pietrenko-Dabrowska Anna , Belen Mehmet A. , Mahouti Peyman 
Published: January 2023

AbstractAccurate models of scattering and noise parameters of transistors are instrumental in facilitating design procedures of microwave devices such as low-noise amplifiers. Yet, data-driven modeling of transistors is a challenging endeavor due to complex relationships between transistor characteristics and its designable parameters, biasing conditions, and frequency. Artificial neural network (ANN)-based methods, including deep learning (DL), have been found suitable for this task by capitalizing on their flexibility and generality. Yet, rendering reliable transistor surrogates is hindered by a number of issues such as the need for finding good match between the input data and the network architecture and hyperparameters (number and sizes of layers, activation functions, data pre-processing methods), possible overtraining, etc. This work proposes a novel methodology, referred to as Fully Adaptive Regression Model (FARM), where all network components and processing functions are automatically determined through Tree Parzen Estimator. Our technique is comprehensively validated using three examples of microwave transistors and demonstrated to offer a competitive edge over the state-of-the-art methods in terms of modeling accuracy and handling the aforementioned issues pertinent to standard ANN-based surrogates.