bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection
Authors: Jaiswal Rishi Kumar , Lei Kai-Hang , Chastain Megan , Wang Yuan , Shiva Olga , Li Shan , You Zhongsheng , Chi Peter , Chai Weihang 
Published: November 2023

AbstractKeeping replication fork stable is essential for safeguarding genome integrity; hence, its protection is highly regulated. The CTC1-STN1-TEN1 (CST) complex protects stalled forks from aberrant MRE11-mediated nascent strand DNA degradation (NSD). However, the activation mechanism for CST at forks is unknown. Here, we report that STN1 is phosphorylated in its intrinsic disordered region. Loss of STN1 phosphorylation reduces the replication stress-induced STN1 localization to stalled forks, elevates NSD, increases MRE11 access to stalled forks, and decreases RAD51 localization at forks, leading to increased genome instability under perturbed DNA replication condition. STN1 is phosphorylated by both the ATR-CHK1 and the calcium-sensing kinase CaMKK2 in response to hydroxyurea/aphidicolin treatment or elevated cytosolic calcium concentration. Cancer-associated STN1 variants impair STN1 phosphorylation, conferring inability of fork protection. Collectively, our study uncovers that CaMKK2 and ATR-CHK1 target STN1 to enable its fork protective function, and suggests an important role of STN1 phosphorylation in cancer development.
Long-range atmospheric transport of microplastics across the southern hemisphere
Authors: Chen Qiqing , Shi Guitao , Revell Laura E. , Zhang Jun , Zuo Chencheng , Wang Danhe , Le Ru Eric C. , Wu Guangmei , Mitrano Denise M. 
Published: November 2023

AbstractAirborne microplastics (MPs) can undergo long range transport to remote regions. Yet there is a large knowledge gap regarding the occurrence and burden of MPs in the marine boundary layer, which hampers comprehensive modelling of their global atmospheric transport. In particular, the transport efficiency of MPs with different sizes and morphologies remains uncertain. Here we show a hemispheric-scale analysis of airborne MPs along a cruise path from the mid-Northern Hemisphere to Antarctica. We present the inaugural measurements of MPs concentrations over the Southern Ocean and interior Antarctica and find that MPs fibers are transported more efficiently than MPs fragments along the transect, with the transport dynamics of MPs generally similar to those of non-plastic particles. Morphology is found to be the dominant factor influencing the hemispheric transport of MPs to remote Antarctic regions. This study underlines the importance of long-range atmospheric transport in MPs cycling dynamics in the environment.
Design for improving corrosion resistance of duplex stainless steels by wrapping inclusions with niobium armour
Authors: Zhang Shucai , Feng Hao , Li Huabing , Jiang Zhouhua , Zhang Tao , Zhu Hongchun , Lin Yue , Zhang Wei , Li Guoping 
Published: November 2023

AbstractUnavoidable nonmetallic inclusions generated in the steelmaking process are fatal defects that often cause serious corrosion failure of steel, leading to catastrophic accidents and huge economic losses. Over the past decades, extensive efforts have been made to address this difficult issue, but none of them have succeeded. Here, we propose a strategy of wrapping deleterious inclusions with corrosion-resistant niobium armour (Z phase). After systematic theoretical screening, we introduce minor Nb into duplex stainless steels (DSSs) to form inclusion@Z core-shell structures, thus isolating the inclusions from corrosive environments. Additionally, both the Z phase and its surrounding matrix possess excellent corrosion resistance. Thus, this strategy effectively prevents corrosion caused by inclusions, thereby doubly improving the corrosion resistance of DSSs. Our strategy overcomes the long-standing problem of “corrosion failure caused by inclusions”, and it is verified as a universal technique in a series of DSSs and industrial production.
A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains
Authors: Sziraki Andras , Lu Ziyu , Lee Jasper , Banyai Gabor , Anderson Sonya , Abdulraouf Abdulraouf , Metzner Eli , Liao Andrew , Banfelder Jason , Epstein Alexander , Schaefer Chloe , Xu Zihan , Zhang Zehao , Gan Li , Nelson Peter T. , Zhou Wei , Cao Junyue 
Published: November 2023

AbstractConventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular dynamics in the mammalian brain. Profiling approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles across diverse mouse brains, we identified over 300 cell subtypes, uncovering their molecular characteristics and spatial locations. This comprehensive view elucidates rare cell types expanded or depleted upon aging. We also investigated cell-type-specific responses to genetic alterations linked to Alzheimer’s disease, identifying associated rare cell types. Additionally, by profiling 118,240 human brain single-cell transcriptomes, we discerned cell- and region-specific transcriptomic changes tied to Alzheimer’s pathogenesis. In conclusion, this research offers a valuable resource for probing cell-type-specific dynamics in both normal and pathological aging.
The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells
Authors: Koh Gene Ching Chiek , Boushaki Soraya , Zhao Salome Jingchen , Pregnall Andrew Marcel , Sadiyah Firas , Badja Cherif , Memari Yasin , Georgakopoulos-Soares Ilias , Nik-Zainal Serena 
Published: November 2023

AbstractThe chemotherapeutic agent CX-5461, or pidnarulex, has been fast-tracked by the United States Food and Drug Administration for early-stage clinical studies of BRCA1-, BRCA2- and PALB2-mutated cancers. It is under investigation in phase I and II trials. Here, we find that, although CX-5461 exhibits synthetic lethality in BRCA1-/BRCA2-deficient cells, it also causes extensive, nonselective, collateral mutagenesis in all three cell lines tested, to magnitudes that exceed known environmental carcinogens.
StayGold variants for molecular fusion and membrane-targeting applications
Authors: Ando Ryoko , Shimozono Satoshi , Ago Hideo , Takagi Masatoshi , Sugiyama Mayu , Kurokawa Hiroshi , Hirano Masahiko , Niino Yusuke , Ueno Go , Ishidate Fumiyoshi , Fujiwara Takahiro , Okada Yasushi , Yamamoto Masaki , Miyawaki Atsushi 
Published: November 2023

AbstractAlthough StayGold is a bright and highly photostable fluorescent protein, its propensity for obligate dimer formation may hinder applications in molecular fusion and membrane targeting. To attain monovalent as well as bright and photostable labeling, we engineered tandem dimers of StayGold to promote dispersibility. On the basis of the crystal structure of this fluorescent protein, we disrupted the dimerization to generate a monomeric variant that offers improved photostability and brightness compared to StayGold. We applied the new monovalent StayGold tools to live-cell imaging experiments using spinning-disk laser-scanning confocal microscopy or structured illumination microscopy. We achieved cell-wide, high-spatiotemporal resolution and sustained imaging of dynamic subcellular events, including the targeting of endogenous condensin I to mitotic chromosomes, the movement of the Golgi apparatus and its membranous derivatives along microtubule networks, the distribution of cortical filamentous actin and the remolding of cristae membranes within mobile mitochondria.
System-wide analysis of RNA and protein subcellular localization dynamics
Authors: Villanueva Eneko , Smith Tom , Pizzinga Mariavittoria , Elzek Mohamed , Queiroz Rayner M. L. , Harvey Robert F. , Breckels Lisa M. , Crook Oliver M. , Monti Mie , Dezi Veronica , Willis Anne E. , Lilley Kathryn S. 
Published: November 2023

AbstractAlthough the subcellular dynamics of RNA and proteins are key determinants of cell homeostasis, their characterization is still challenging. Here we present an integrative framework to simultaneously interrogate the dynamics of the transcriptome and proteome at subcellular resolution by combining two methods: localization of RNA (LoRNA) and a streamlined density-based localization of proteins by isotope tagging (dLOPIT) to map RNA and protein to organelles (nucleus, endoplasmic reticulum and mitochondria) and membraneless compartments (cytosol, nucleolus and cytosolic granules). Interrogating all RNA subcellular locations at once enables system-wide quantification of the proportional distribution of RNA. We obtain a cell-wide overview of localization dynamics for 31,839 transcripts and 5,314 proteins during the unfolded protein response, revealing that endoplasmic reticulum-localized transcripts are more efficiently recruited to cytosolic granules than cytosolic RNAs, and that the translation initiation factor eIF3d is key to sustaining cytoskeletal function. Overall, we provide the most comprehensive overview so far of RNA and protein subcellular localization dynamics.
Relationship between klotho and physical function in healthy aging
Authors: Arroyo Eliott , Leber Cecilia A. , Burney Heather N. , Narayanan Gayatri , Moorthi Ranjani , Avin Keith G. , Warden Stuart J. , Moe Sharon M. , Lim Kenneth 
Published: November 2023

AbstractEpidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.
Understanding the impact of acne vulgaris and associated psychological distress on self-esteem and quality of life via regression modeling with CADI, DLQI, and WHOQoL
Authors: Morshed A. S. M. , Noor Towhida , Uddin Ahmed Md Ashraf , Mili Fahmida Sultana , Ikram Shuma , Rahman Mashiqur , Ahmed Shamim , Uddin Mohammad Borhan 
Published: November 2023

AbstractAcne vulgaris (AV) is a psychosomatic disorder and can negatively affect individuals, especially in terms of psychological well-being, self-esteem, and quality of life (QoL). The current study aimed to investigate the association between AV and psychological health, as well as the influence of acne and psychological distress in predicting patients' self-esteem and QoL. This cross-sectional study included 150 patients clinically diagnosed with AV. The severity of acne was measured using GAGS, and following that, patients were instructed to complete the following forms: DASS-21, RSES, CADI, DLQI, and WHOQoL. Female AV patients had significantly higher depression (p = 0.003, t = 3.025) and anxiety (p < 0.001, t = 3.683). Pearson's correlation analysis indicated a strong, positive, and significant correlation between having acne and experiencing depression (r = 0.630), anxiety (r = 0.661), and stress (r = 0.758) (p < 0.001). Multiple regression analysis suggested acne and associated psychological distress had a significant and negative impact on the patient's self-esteem and quality of life. This study highlights the multifaceted consequences of AV and the need to manage its psychological distress. It emphasizes the need for holistic patient care that addresses acne's physical and emotional aspects, with the ultimate goal of enhancing well-being and QoL.
A machine learning-assisted system to predict thyrotoxicosis using patients’ heart rate monitoring data: a retrospective cohort study
Authors: Shin Kyubo , Kim Jongchan , Park Jaemin , Oh Tae Jung , Kong Sung Hye , Ahn Chang Ho , Moon Joon Ho , Kim Min Joo , Moon Jae Hoon 
Published: November 2023

AbstractPrevious studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)-assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients. HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with thyroid dysfunction. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML-assisted system predicted thyrotoxicosis of a patient at a given time point based on HR data and their HR-TFT data pair at another time point. Our ML-assisted system divided the 662 cases into either thyrotoxicosis and non-thyrotoxicosis and the performance was calculated based on the TFT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 86.14%, 85.92%, 52.41%, and 97.18%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 86.14%, 98.28%, 94.57%, and 95.32%, respectively. Our ML-assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen–Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis. Our ML-assisted system has demonstrated reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction, and the accuracy could be further improved by gathering more data. This predictive system has the potential to monitor the thyroid function status of patients with thyroid dysfunction by collecting heart rate data, and to determine the optimal timing for blood tests and treatment intervention.
The effects of exposure to O2- and HOCl-nanobubble water on human salivary microbiota
Authors: Sagara Ken , Kataoka Shota , Yoshida Akihiro , Ansai Toshihiro 
Published: November 2023

AbstractNanobubbles of gas remain dissolved in water for longer periods than ordinary bubbles, and exhibit unique physicochemical and biological properties. As a result, nanobubble water (NBW) is finding widespread use many applications, such as cleaning in the industry and purification of lake water. The ozone NBW (O3-NBW), in particular, has been used in clinical dentistry; however, it has several disadvantages, including the instability of ozone, which is spontaneously converted to molecular oxygen (O3 to O2), and its broad range of antibacterial activity, which can disrupt the oral microbiota. Therefore, the use of NBW in dental medicine requires greater evaluation. Here, we examined the effects of oxygen and hypochlorite NBW (O2-NBW and HOCl-NBW, respectively) on the microbiota in human saliva in 16 male patients (35–75 years old; median: 53.5 years) using multiple assays, including next generation sequencing analysis. 16S rRNA gene sequencing revealed no significant changes in both alpha-diversity and beta-diversity. Principal Coordinate Analysis (PCoA) revealed two subclusters in both unweighted and weighted UniFrac distances. Overall, the results revealed that HOCl-NBW exposure of saliva may lead to inhibition or delay in oral biofilm formation while maintaining the balance of the oral microbiome. These results can lead to the development of a novel type of mouthrinse for prevention of oral infectious diseases.
Heterogeneous slab thermal dehydration driving warm subduction zone earthquakes
Authors: Zhu Ye , Ji Yingfeng , Liu Lijun , Zhu Weiling , Qu Rui , Xie Chaodi , Faheem Haris , Yoshioka Shoichi , Ding Lin 
Published: November 2023

AbstractChanging thermal regime is one of the key mechanisms driving seismogenic behaviors at cold megathrusts, but it is difficult to interpret warm subduction zones such as Vanuatu for the temperatures are higher than that accommodates shallow brittle failures. We construct a 3-D thermomechanical model to clarify the thermal structure that controls tectonic seismicity in Vanuatu and predict a warm circumstance associated with abundant seismicity. Results reveal a heterogeneous slab ranging from 300 °C to over 900 °C from the Moho to subvolcanic depth. The subduction seismicity corresponds well to the plate interface where dynamic thermal dehydration is focused. The transformation from hydrated basalts to eclogites along the slab facilitates the occurrence of intense earthquakes and slips. Multistage mineralogical metamorphism affects the dynamic stability of megathrusts and favors the generation of active interplate large events. Therefore, slab thermal dehydration plays a greater role than slab temperature condition in influencing the subduction earthquake distribution in warm subduction systems.
Leptin antagonism attenuates hypertension and renal injury in an experimental model of autoimmune disease
Authors: Kalusche William J. , Case Clinton T. , Taylor Erin B. 
Published: November 2023

Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by B- and T-lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin. Leptin has various immunomodulatory properties, including promoting the expansion of proinflammatory T lymphocytes and the proliferation and survival of B cells. In the present study, we hypothesized that leptin antagonism would improve B- and T-cell dysfunction and attenuate hypertension in an experimental model of SLE, the NZBWF1 mouse. To test this hypothesis, 28-week-old female control and SLE mice were administered 5 mg/kg of murine leptin superantagonist (LA) or vehicle via ip injection every other day for four weeks. Analysis of peripheral blood immune cell populations showed no changes in total CD45R+ B and CD3+ T cell percentages after treatment with LA. However, SLE mice treated with LA had an improved CD4/CD8 ratio and decreased CD3+CD4−CD8− double negative (DN) T cells. Blood pressure was higher in SLE than in control, and treatment with LA decreased blood pressure in SLE mice. Treatment with LA also delayed the onset of albuminuria and decreased glomerulosclerosis in SLE mice. Renal immune cell infiltration was significantly higher in SLE mice as compared with control, but LA treatment was associated with decreased levels of renal CD4+ T cells. In conclusion, these data suggest that leptin plays a pathogenic role in the development of hypertension in SLE, in part, by promoting the expansion of inflammatory DN T cells and the infiltration of T cells into the kidneys.
Exploring the nature of ultra-luminous X-ray sources across stellar population ages using detailed binary evolution calculations
Authors: Misra Devina , Kovlakas Konstantinos , Fragos Tassos , Andrews Jeff J. , Bavera Simone S. , Zapartas Emmanouil , Xing Zepei , Dotter Aaron , Rocha Kyle Akira , Srivastava Philipp M. , Sun Meng 
Published: November 2023

Context. Ultra-luminous X-ray sources (ULXs) are sources observed to have extreme X-ray luminosities exceeding the Eddington limit of a stellar-mass black hole (BH). A fraction of ULXs show X-ray pulsations, which are evidence for accreting neutron stars (NSs). Theoretical studies have suggested that NSs, rather than BHs, dominate the compact objects of intrinsic ULX populations, even though the majority of the observed sample is non-pulsating, implying that X-ray pulses from many NS ULXs are unobservable.
Aims. We simulate populations of X-ray binaries covering a range of starburst ages spanning from 5 to 1000 Myr with the aim of comparing the properties of observed ULXs at the different ages. Additionally, we compare two models describing different assumptions for the physical processes governing binary evolution.
Methods. We used the new population synthesis code POSYDON to generate multiple populations of ULXs spanning multiple burst ages. We employed a model for geometrically beamed emission from a super-Eddington accretion disk in order to estimate the luminosities of ULXs. Following theoretical predictions for the alignment of the spin axis of an NS with the accretion disk due to mass transfer, we estimated the required mass to be accreted by the NSs in the ULX populations so that the alignment suppresses observable X-ray pulses.
Results. While we find that the properties of ULX populations are sensitive to model assumptions, there are certain trends that the populations follow. Generally, young and old stellar populations are dominated by BH and NS accretors, respectively. The donor stars go from being massive H-rich main-sequence stars in young populations (< 100 Myr) to low-mass post-main sequence H-rich stars in older populations (> 100 Myr), with stripped He-rich giant donors dominating the populations at around 100 Myr. In addition, we find that NS ULXs exhibit stronger geometrical beaming than BH ULXs, leading to an underrepresentation of NS accretors in observed populations. Coupled with our finding that X-ray pulses are suppressed in at least 60% of the NS ULXs, we suggest that the observed fraction of ULXs with detectable X-ray pulses is very small, in agreement with observations.
Conclusions. We show that geometrical beaming and the mass-accretion phase are critical aspects of understanding ULX observations. Our results suggest that even though most ULXs have accreting NSs, those with observable X-ray pulses would be very few.
Methodology for obtaining the relative orbit and individual masses of Gaia astrometric binaries
Authors: Pérez-Couto X. , Docobo J. Á. , Campo P. P. 
Published: November 2023

Context. The recent Gaia Data Release 3 has revealed a catalogue of more than eight hundred thousand binary systems. The release provides orbital solutions for half of the systems, with the majority of them being unresolved astrometric binaries. However, some astrophysical parameters are still unknown for most of them, such as the spectral type and the mass of each companion, since they can only be derived from the relative orbit and spectroscopic data.
Aims. The purpose of this work is to develop a methodology that would allow us to obtain those fundamental stellar parameters, along with those related to the geometry and the ephemeris of the system, to find out whether it can be optically resolved.
Methods. To obtain precise values for each component, we proposed an analytic algorithm to estimate the only two possible relative orbits and pairs of masses of main sequence (MS) astrometric binaries using all the available astrometric, photometric, and spectro-scopic data from Gaia DR3. In some cases, it is possible to select the solution that is more aligned with the rest of the data.
Results. We deduced two possible values for the individual absolute magnitudes, masses, and effective temperatures for each binary, as well as the size of the telescope necessary to resolve their components. We present the workflow of our algorithm applied to the Ephemeris, Stellar Masses, and relative ORbits from GAia (ESMORGA) catalogue, along with the individual masses, absolute magnitudes, and effective temperatures derived for 49 530 binaries.