bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting DNA structure using a deep learning method
Authors: Li Jinsen , Chiu Tsu-Pei , Rohs Remo 
Published: February 2024

AbstractUnderstanding the mechanisms of protein-DNA binding is critical in comprehending gene regulation. Three-dimensional DNA structure, also described as DNA shape, plays a key role in these mechanisms. In this study, we present a deep learning-based method, Deep DNAshape, that fundamentally changes the current k-mer based high-throughput prediction of DNA shape features by accurately accounting for the influence of extended flanking regions, without the need for extensive molecular simulations or structural biology experiments. By using the Deep DNAshape method, DNA structural features can be predicted for any length and number of DNA sequences in a high-throughput manner, providing an understanding of the effects of flanking regions on DNA structure in a target region of a sequence. The Deep DNAshape method provides access to the influence of distant flanking regions on a region of interest. Our findings reveal that DNA shape readout mechanisms of a core target are quantitatively affected by flanking regions, including extended flanking regions, providing valuable insights into the detailed structural readout mechanisms of protein-DNA binding. Furthermore, when incorporated in machine learning models, the features generated by Deep DNAshape improve the model prediction accuracy. Collectively, Deep DNAshape can serve as versatile and powerful tool for diverse DNA structure-related studies.
Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function
Authors: Tian Chenxi , Wang Yu , Su Miya , Huang Yuanyuan , Zhang Yuwei , Dou Jiaxiang , Zhao Changfeng , Cai Yuting , Pan Jun , Bai Shiyu , Wu Qielan , Chen Sanwei , Li Shuhang , Xie Di , Lv Rong , Chen Yusheng , Wang Yucai , Fu Sicheng , Zhang Huimin , Bai Li 
Published: February 2024

AbstractDysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.
CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes
Authors: Jilani Sameeha , Saco Justin D. , Mugarza Edurne , Pujol-Morcillo Aleida , Chokry Jeffrey , Ng Clement , Abril-Rodriguez Gabriel , Berger-Manerio David , Pant Ami , Hu Jane , Gupta Rubi , Vega-Crespo Agustin , Baselga-Carretero Ignacio , Chen Jia M. , Shin Daniel Sanghoon , Scumpia Philip , Radu Roxana A. , Chen Yvonne , Ribas Antoni , Puig-Saus Cristina 
Published: February 2024

AbstractA major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial.
Using the heme peroxidase APEX2 to probe intracellular H2O2 flux and diffusion
Authors: Eid Mohammad , Barayeu Uladzimir , Sulková Kateřina , Aranda-Vallejo Carla , Dick Tobias P. 
Published: February 2024

AbstractCurrently available genetically encoded H2O2 probes report on the thiol redox state of the probe, which means that they reflect the balance between probe thiol oxidation and reduction. Here we introduce the use of the engineered heme peroxidase APEX2 as a thiol-independent chemogenetic H2O2 probe that directly and irreversibly converts H2O2 molecules into either fluorescent or luminescent signals. We demonstrate sensitivity, specificity, and the ability to quantitate endogenous H2O2 turnover. We show how the probe can be used to detect changes in endogenous H2O2 generation and to assess the roles and relative contributions of endogenous H2O2 scavengers. Furthermore, APEX2 can be used to study H2O2 diffusion inside the cytosol. Finally, APEX2 reveals the impact of commonly used alkylating agents and cell lysis protocols on cellular H2O2 generation.
Mapping the global distribution of C4 vegetation using observations and optimality theory
Authors: Luo Xiangzhong , Zhou Haoran , Satriawan Tin W. , Tian Jiaqi , Zhao Ruiying , Keenan Trevor F. , Griffith Daniel M. , Sitch Stephen , Smith Nicholas G. , Still Christopher J. 
Published: February 2024

AbstractPlants with the C4 photosynthesis pathway typically respond to climate change differently from more common C3-type plants, due to their distinct anatomical and biochemical characteristics. These different responses are expected to drive changes in global C4 and C3 vegetation distributions. However, current C4 vegetation distribution models may not predict this response as they do not capture multiple interacting factors and often lack observational constraints. Here, we used global observations of plant photosynthetic pathways, satellite remote sensing, and photosynthetic optimality theory to produce an observation-constrained global map of C4 vegetation. We find that global C4 vegetation coverage decreased from 17.7% to 17.1% of the land surface during 2001 to 2019. This was the net result of a reduction in C4 natural grass cover due to elevated CO2 favoring C3-type photosynthesis, and an increase in C4 crop cover, mainly from corn (maize) expansion. Using an emergent constraint approach, we estimated that C4 vegetation contributed 19.5% of global photosynthetic carbon assimilation, a value within the range of previous estimates (18–23%) but higher than the ensemble mean of dynamic global vegetation models (14 ± 13%; mean ± one standard deviation). Our study sheds insight on the critical and underappreciated role of C4 plants in the contemporary global carbon cycle.
Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment
Authors: Juul-Madsen Kristian , Parbo Peter , Ismail Rola , Ovesen Peter L. , Schmidt Vanessa , Madsen Lasse S. , Thyrsted Jacob , Gierl Sarah , Breum Mihaela , Larsen Agnete , Andersen Morten N. , Romero-Ramos Marina , Holm Christian K. , Andersen Gregers R. , Zhao Huaying , Schuck Peter , Nygaard Jens V. , Sutherland Duncan S. , Eskildsen Simon F. , Willnow Thomas E. , Brooks David J. , Vorup-Jensen Thomas 
Published: February 2024

AbstractThe peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis.
Meiotic recombination dynamics in plants with repeat-based holocentromeres shed light on the primary drivers of crossover patterning
Authors: Castellani Marco , Zhang Meng , Thangavel Gokilavani , Mata-Sucre Yennifer , Lux Thomas , Campoy José A. , Marek Magdalena , Huettel Bruno , Sun Hequan , Mayer Klaus F. X. , Schneeberger Korbinian , Marques André 
Published: February 2024

AbstractCentromeres strongly affect (epi)genomic architecture and meiotic recombination dynamics, influencing the overall distribution and frequency of crossovers. Here we show how recombination is regulated and distributed in the holocentric plant Rhynchospora breviuscula, a species with diffused centromeres. Combining immunocytochemistry, chromatin analysis and high-throughput single-pollen sequencing, we discovered that crossover frequency is distally biased, in sharp contrast to the diffused distribution of hundreds of centromeric units and (epi)genomic features. Remarkably, we found that crossovers were abolished inside centromeric units but not in their proximity, indicating the absence of a canonical centromere effect. We further propose that telomere-led synapsis of homologues is the feature that best explains the observed recombination landscape. Our results hint at the primary influence of mechanistic features of meiotic pairing and synapsis rather than (epi)genomic features and centromere organization in determining the distally biased crossover distribution in R. breviuscula, whereas centromeres and (epi)genetic properties only affect crossover positioning locally.
Artificial-goosebump-driven microactuation
Authors: Zhang Mingchao , Pal Aniket , Lyu Xianglong , Wu Yingdan , Sitti Metin 
Published: February 2024

AbstractMicroactuators provide controllable driving forces for precise positioning, manipulation and operation at the microscale. Development of microactuators using active materials is often hampered by their fabrication complexity and limited motion at small scales. Here we report light-fuelled artificial goosebumps to actuate passive microstructures, inspired by the natural reaction of hair bristling (piloerection) on biological skin. We use light-responsive liquid crystal elastomers as the responsive artificial skin to move three-dimensionally printed passive polymer microstructures. When exposed to a programmable femtosecond laser, the liquid crystal elastomer skin generates localized artificial goosebumps, resulting in precise actuation of the surrounding microstructures. Such microactuation can tilt micro-mirrors for the controlled manipulation of light reflection and disassemble capillary-force-induced self-assembled microstructures globally and locally. We demonstrate the potential application of the proposed microactuation system for information storage. This methodology provides precise, localized and controllable manipulation of microstructures, opening new possibilities for the development of programmable micromachines.
Bragg glass signatures in PdxErTe3 with X-ray diffraction temperature clustering
Authors: Mallayya Krishnanand , Straquadine Joshua , Krogstad Matthew J. , Bachmann Maja D. , Singh Anisha G. , Osborn Raymond , Rosenkranz Stephan , Fisher Ian R. , Kim Eun-Ah 
Published: February 2024

AbstractThe Bragg glass phase is a nearly perfect crystal with glassy features predicted to occur in vortex lattices and charge-density-wave systems in the presence of disorder. Detecting it has been challenging, despite its sharp theoretical definition in terms of diverging correlation lengths. Here we present bulk probe evidence supporting a Bragg glass phase in the systematically disordered charge-density-wave material of PdxErTe3. We do this by using comprehensive X-ray data and a machine-learning-based analysis tool called X-ray diffraction temperature clustering (X-TEC). We establish a diverging correlation length in samples with moderate intercalation over a wide temperature range. To enable this analysis, we introduced a high-throughput measure of inverse correlation length that we call peak spread. The detection of Bragg glass order and the resulting phase diagram advance our understanding of the complex interplay between disorder and fluctuations. Moreover, the use of our analysis technique to target fluctuations through a high-throughput measure of peak spread can revolutionize the study of fluctuations in scattering experiments.
Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection
Authors: Ying Baoling , Darling Tamarand L. , Desai Pritesh , Liang Chieh-Yu , Dmitriev Igor P. , Soudani Nadia , Bricker Traci , Kashentseva Elena A. , Harastani Houda , Raju Saravanan , Liu Meizi , Schmidt Aaron G. , Curiel David T. , Boon Adrianus C. M. , Diamond Michael S. 
Published: February 2024

AbstractA nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8+ T cells before XBB.1.5 challenge resulted in loss of protection against upper and lower respiratory tract infection. Thus, nasally delivered vaccines stimulate mucosal immunity against emerging SARS-CoV-2 strains, and cross-reactive memory CD8+ T cells mediate protection against lung infection by antigenically distant strains in the setting of low serum levels of cross-reactive neutralizing antibodies.
JH-2 constitutive model of sandstone for dynamic problems
Authors: Baranowski Paweł , Kucewicz Michał , Janiszewski Jacek 
Published: February 2024

AbstractThis paper demonstrates the application of the Johnson–Holmquist II (JH-2) model with correlated and validated parameters to simulate the behavior of a sandstone. The JH-2 model is used to simulate various tests, including single-element tests, structural quasi-static uniaxial and triaxial compression tests, and the split Hopkinson pressure bar test. Additionally, the model is used to simulate drop-weight impact test using a ball bearing and two loading scenarios involving small-scale blasting and projectile impacts. Quantitative and qualitative comparisons demonstrate that the JH-2 model agrees well with both experimental and analytical results. Limitations of the model are also highlighted, particularly for quasi-static problems, as the model was originally developed for high-strain-rate simulations. Ultimately, this study demonstrates that the JH-2 rock constitutive model can obtain reasonable results for a material other than the material for which the model was originally correlated and validated. This paper provides valuable guidance for modeling and simulating sandstone and other rock materials subjected to dynamic loadings.
Pilot study on cultural and metagenomic analysis of bile and biliary stentslead to unveiling the key players in stent occlusion
Authors: Cacaci Margherita , De Maio Flavio , Matteo Maria Valeria , Posteraro Brunella , Di Vito Maura , Menchinelli Giulia , Tringali Andrea , Monzo Francesca Romana , Torelli Riccardo , Costamagna Guido , Spada Cristiano , Bugli Francesca , Sanguinetti Maurizio , Boskoski Ivo 
Published: February 2024

AbstractEndoscopic Retrograde Cholangio-Pancreatography (ERCP) with biliary stenting is a minimally invasive medical procedure employed to address both malignant and benign obstructions within the biliary tract. Benign biliary strictures (BBSs), typically arising from surgical interventions such as liver transplants and cholecystectomy, as well as chronic inflammatory conditions, present a common clinical challenge. The current gold standard for treating BBSs involves the periodic insertion of plastic stents at intervals of 3–4 months, spanning a course of approximately one year. Unfortunately, stent occlusion emerges as a prevalent issue within this treatment paradigm, leading to the recurrence of symptoms and necessitating repeated ERCPs. In response to this clinical concern, we initiated a pilot study, delving into the microbial composition present in bile and on the inner surfaces of plastic stents. This investigation encompassed 22 patients afflicted by BBSs who had previously undergone ERCP with plastic stent placement. Our preliminary findings offered promising insights into the microbial culprits behind stent occlusion, with Enterobacter and Lactobacillus spp. standing out as prominent bacterial species known for their biofilm-forming tendencies on stent surfaces. These revelations hold promise for potential interventions, including targeted antimicrobial therapies aimed at curtailing bacterial growth on stents and the development of advanced stent materials boasting anti-biofilm properties.
Demonstration of nuclear gamma-ray polarimetry based on a multi-layer CdTe Compton camera
Authors: Go S. , Tsuzuki Y. , Yoneda H. , Ichikawa Y. , Ikeda T. , Imai N. , Imamura K. , Niikura M. , Nishimura D. , Mizuno R. , Takeda S. , Ueno H. , Watanabe S. , Saito T. Y. , Shimoura S. , Sugawara S. , Takamine A. , Takahashi T. 
Published: February 2024

AbstractTo detect and track structural changes in atomic nuclei, the systematic study of nuclear levels with firm spin-parity assignments is important. While linear polarization measurements have been applied to determine the electromagnetic character of gamma-ray transitions, the applicable range is strongly limited due to the low efficiency of the detection system. The multi-layer Cadmium-Telluride (CdTe) Compton camera can be a state-of-the-art gamma-ray polarimeter for nuclear spectroscopy with the high position sensitivity and the detection efficiency. We demonstrated the capability to operate this detector as a reliable gamma-ray polarimeter by using polarized 847-keV gamma rays produced by the $$^{56}\textrm{Fe}$$

56

Fe

($${ p},{ p'}\gamma $$

p
,

p
′

γ

) reaction. By combining the experimental data and simulated calculations, the modulation curve for the gamma ray was successfully obtained. A remarkably high polarization sensitivity was achieved, compatible with a reasonable detection efficiency. Based on the obtained results, a possible future gamma-ray polarimetery is discussed.
Atmospheric formaldehyde production on early Mars leading to a potential formation of bio-important molecules
Authors: Koyama Shungo , Kamada Arihiro , Furukawa Yoshihiro , Terada Naoki , Nakamura Yuki , Yoshida Tatsuya , Kuroda Takeshi , Vandaele Ann Carine 
Published: February 2024

AbstractFormaldehyde (H2CO) is a critical precursor for the abiotic formation of biomolecules, including amino acids and sugars, which are the building blocks of proteins and RNA. Geomorphological and geochemical evidence on Mars indicates a temperate environment compatible with the existence of surface liquid water during its early history at 3.8–3.6 billion years ago (Ga), which was maintained by the warming effect of reducing gases, such as H2. However, it remains uncertain whether such a temperate and weakly reducing surface environment on early Mars was suitable for producing H2CO. In this study, we investigated the atmospheric production of H2CO on early Mars using a 1-D photochemical model assuming a thick CO2-dominated atmosphere with H2 and CO. Our results show that a continuous supply of atmospheric H2CO can be used to form various organic compounds, including amino acids and sugars. This could be a possible origin for the organic matter observed on the Martian surface. Given the previously reported conversion rate from H2CO into ribose, the calculated H2CO deposition flux suggests a continuous supply of bio-important sugars on early Mars, particularly during the Noachian and early Hesperian periods.
Resource choice during ontogeny enhances both the short- and longer-term welfare of laying hen pullets
Authors: Holt Regine Victoria , Skånberg Lena , Keeling Linda J. , Estevez Inma , Newberry Ruth C. 
Published: February 2024

AbstractWe hypothesised that resource choice during early life contributes to both current and longer-term beneficial effects on animal welfare. We investigated this hypothesis in a longitudinal cross-over experiment with laying hen pullets (Gallus gallus domesticus) reared in pens with one or four litter and perch types, respectively (n = 8 pens/treatment, all providing ample and identical litter and perch space). After 4 weeks (chick period), half the pens were modified to provide the opposite treatment (juvenile period). After 11 more weeks, all groups were moved to novel, identical laying pens (adult period; Week 16–27). In support of our hypothesis, the opportunity to choose between multiple litter and perch variants was associated with higher levels of positively-valenced behaviours, including play as chicks and dustbathing as juveniles and adults, and lower levels of negatively-valenced behaviours, including feather pecking as chicks and juveniles and aggressive pecking as adults. Resource choice in the juvenile period also led to better juvenile and adult plumage condition, and greater growth as adults. We conclude that the opportunity to choose among different litter and perch types, instead of having only one type of each, had both short- and longer-term positive effects on the birds’ affective states and physical condition.
Assessing the effects of pandemic risk on cooperation and social norms using a before-after Covid-19 comparison in two long-term experiments
Authors: Vriens Eva , Szekely Aron , Lipari Francesca , Antonioni Alberto , Sánchez Angel , Tummolini Luca , Andrighetto Giulia 
Published: February 2024

AbstractHow does threat from disease shape our cooperative actions and the social norms that guide such behaviour? To study these questions, we draw on a collective-risk social dilemma experiment that we ran before the emergence of the Covid-19 pandemic (Wave 1, 2018) and compare this to its exact replication, sampling from the same population, that we conducted during the first wave of the pandemic (Wave 2, 2020). Tightness-looseness theory predicts and evidence generally supports that both cooperation and accompanying social norms should increase, yet, we mostly did not find this. Contributions, the probability of reaching the threshold (cooperation), and the contents of the social norm (how much people should contribute) remained similar across the waves, although the strength of these social norms were slightly greater in Wave 2. We also study whether the results from Wave 1 that should not be affected by the pandemic—the relationship between social norms and cooperation and specific behavioural types—replicate in Wave 2 and find that these results generally hold. Overall, our work demonstrates that social norms are important drivers of cooperation, yet, communicable diseases, at least in the short term, have little or no effects on either.