bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation
Authors: Kobaisi Farah , Sulpice Eric , Nasrallah Ali , Obeïd Patricia , Fayyad-Kazan Hussein , Rachidi Walid , Gidrol Xavier 
Published: November 2024

AbstractXeroderma Pigmentosum C is a dermal hereditary disease caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients display heightened sensitivity to light and an inability to mend DNA damage caused by UV radiation, resulting in the accumulation of lesions that can transform into mutations and eventually lead to cancer. To address this issue, we conducted a screening of siRNAs targeting human kinases, given their involvement in various DNA repair pathways, aiming to restore normal cellular behavior. We introduced this siRNA library into both normal and XPC patient-derived fibroblasts, followed by UVB exposure to induce DNA damage. We assessed the reversal of the XPC phenotype by measuring reduced photosensitivity and enhanced DNA repair. Among the 1292 kinase-targeting siRNAs screened, twenty-eight showed significant improvement in cellular survival compared to cells transfected with non-targeting siRNA after UV exposure in XPC cells. From these candidates, PIK3C3 and LATS1 were identified as particularly effective, promoting over 20% repair of 6-4 photoproduct (6-4PP) DNA lesions. Specifically targeting the autophagy-related protein PIK3C3 alone demonstrated remarkable photoprotective effects in XPC-affected cells, which were validated in primary XPC patient fibroblasts and CRISPR-Cas9 engineered XPC knockout keratinocytes. PIK3C3 knock down in XP-C cells ameliorated in UVB dose response analysis, decreased apoptosis with no effect on proliferation. More importantly, PIK3C3 knock down was found to induce an increase in UVRAG expression, a previously reported cDNA conveying lower photosensitivity in XP-C cells. Thus, attempts to improve the XPC photosensitive and deficient repair phenotype using PIK3C3 inhibitors could pave a way for new therapeutic approaches delaying or preventing tumor initiation.
G12/13-mediated signaling stimulates hepatic glucose production and has a major impact on whole body glucose homeostasis
Authors: Pittala Srinivas , Haspula Dhanush , Cui Yinghong , Yang Won-Mo , Kim Young-Bum , Davis Roger J. , Wing Allison , Rotman Yaron , McGuinness Owen P. , Inoue Asuka , Wess Jürgen 
Published: November 2024

AbstractAltered hepatic glucose fluxes are critical during the pathogenesis of type 2 diabetes. G protein-coupled receptors represent important regulators of hepatic glucose production. Recent studies have shown that hepatocytes express GPCRs that can couple to G12/13, a subfamily of heterotrimeric G proteins that has attracted relatively little attention in the past. Here we show, by analyzing several mutant mouse strains, that selective activation of hepatocyte G12/13 signaling leads to pronounced hyperglycemia and that this effect involves the stimulation of the ROCK1-JNK signaling cascade. Using both mouse and human hepatocytes, we also show that activation of endogenous sphingosine-1-phosphate type 1 receptors strongly promotes glucose release in a G12/13-dependent fashion. Studies with human liver samples indicate that hepatic GNA12 (encoding Gα12) expression levels positively correlate with indices of insulin resistance and impaired glucose homeostasis, consistent with a potential pathophysiological role of enhanced hepatic G12/13 signaling.
A Huluwa phosphorylation switch regulates embryonic axis induction
Authors: Li Yao , Yan Yun , Gong Bo , Zheng Qianwen , Zhou Haiyan , Sun Jiarui , Li Mingpeng , Wang Zhao , Li Yaohui , Wan Yunjing , Chen Weixi , Qi Shiqian , Mo Xianming , Meng Anming , Xiang Bo , Chen Jing 
Published: November 2024

AbstractEmbryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa protein remains unclear. Through candidate screening we identified a mutation at Ser168 in the PPNSP motif of Hwa that dramatically abolishes its axis-inducing activity. Mechanistically, mutating the Ser168 residue reduced its binding affinity to Tankyrase 1/2 and the degradation of the Axin protein, weakening β-catenin signaling activation. We confirmed that Ser168 is phosphorylated and that phosphorylation increases Hwa activity in β-catenin signaling and axis induction. Several kinases including Cdk16, Cdk2, and GSK3β, were found to enhance Ser168 phosphorylation in vitro and in vivo. Both dominant-negative Cdk16 expression and pHwa (Ser168) antibody treatment reduce Hwa function. Lastly, a knock-in allele mutating Ser168 to alanine resulted in embryos lacking body axes, demonstrating that Ser168 is essential to axis formation. In summary, Ser168 acts as a phosphorylation switch in Hwa/β-catenin signaling for embryonic axis induction, regulated by multiple kinases.
Understanding frustration triggers and emotional responses in driving situations
Authors: Yazdi Hannaneh , Wickman Casper , Ljung Aust Mikael , Selbing Ida , Kowalski Leo , Axelsson John 
Published: November 2024

AbstractFrustration is a complex emotional phenomenon subject to various triggers and manifested through multifaceted behavioral and affective responses. This study investigates the relationship between distinct frustration-inducing situations encountered during driving and the corresponding affective responses, focusing on the mediating role of behavioral dimensions. A total of 2244 participants answered a questionnaire on driving behavior, the likelihood of experiencing frustration in various driving situations, and affective responses in frustrating situations. Latent factors and triggers of frustration were determined using Exploratory Factor Analysis, and their relationship to driving behavior was assessed using Multiple Regression Analysis. We identified four primary clusters of situations that could trigger frustration in drivers: Unpredictable Experiences, Achievement Obstacles, Distress Elicitors and External Distractions. The emotions accompanying driver frustration clustered into four distinct dimensions: Irritation, Anxiety, Boredom, and Embarrassment. While anxiety-related emotions were central in all frustrating responses (i.e., all four clusters), the other emotion dimensions were specifically related to some of the frustration clusters. Additionally, different types of frustrating situations were characterized by different emotional responses. Furthermore, having more lapses was related to heightened frustration levels. Unraveling the complexities of frustration may aid in the further further development of traffic safety by attempting to eliminate frequent frustration triggers in driving situations.
Healthy food diversity and the risk of major chronic diseases in the EPIC-Potsdam study
Authors: Nickel Daniela V. , Jannasch Franziska , Inan-Eroglu Elif , Kuxhaus Olga , Schulze Matthias B. 
Published: November 2024

AbstractPracticing a diverse diet may reduce chronic disease risk, but clear evidence is scarce and previous diet diversity measures rarely captured diet quality. We investigated the effect of the Healthy Food Diversity (HFD)-Index on incident type 2 diabetes (T2D), myocardial infarction (MI) and stroke among a middle-aged German population. The EPIC-Potsdam study recruited 27,548 participants from 1994 to 1998. Semiquantitative food frequency questionnaire was used to calculate the HFD-Index. Longitudinal associations of HFD-Index and verified incident diseases were investigated by multiple-adjusted Cox proportional hazards regression models. Among 26,591 participants (mean age 50.5 years, 60% women), 1537, 376 and 412 developed T2D, MI and stroke, respectively, over an average follow-up of 10.6 years. There was no association between HFD-Index and incident T2D or MI. Higher compared to lower HFD-Index was inversely associated with incident stroke in men [HR (95% CI): 0.80 (0.70, 0.92)], but positively associated with incident stroke in women [1.20 (1.01, 1.42)]. Although there was no clear association between HFD-Index and T2D or MI incidence, we found a beneficial association in men and a harmful association in women for incident stroke. We emphasised the need for further investigations on combining diet diversity and diet quality in relation to health outcomes.
Myostatin as a plausible biomarker for early stage of sarcopenic obesity
Authors: Ishibashi Chisaki , Nakanishi Kaori , Nishida Makoto , Shinomiya Haruki , Shinzawa Maki , Kanayama Daisuke , Yamamoto Ryohei , Kudo Takashi , Nagatomo Izumi , Yamauchi-Takihara Keiko 
Published: November 2024

AbstractSince sarcopenic obesity (SO) impacts negatively on our health, early detection of SO is essential. However, prevalence of SO in an apparently healthy population has not been well examined. This study aimed to elucidate the prevalence and related factors of SO in middle-aged women, and to investigate useful diagnostic criteria for SO. Body component analyses were conducted on 432 female Osaka University employees aged 30–59 during their health checkups. Healthy (H) and SO groups were defined using cutoff values of 5.7 kg/m2 for skeletal muscle mass index and 30% for percent body fat. Serum myostatin and insulin levels were additionally measured. Among 432 participants, the prevalence of SO was 6.3%. Grip strength (P < 0.0001) was lower and triglyceride (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0105) levels, and Homeostatic Model Assessment of Insulin Resistance (P = 0.0262) were higher in the SO group than in the H group. Serum myostatin levels in the SO group were lower than in the H group (3,107 pg/mL vs. 3,957 pg/mL, P = 0.0003). Myostatin levels may be suppressed in individuals with SO without any pre-existing conditions. Our diagnostic criteria for SO could reveal the risks for metabolic-related diseases and may be useful for the early detection of SO.
Validation of SSR markers for identification of high-yielding and Phytophthora Capsici root rot resistant chilli genotypes
Authors: Bukhari Tazien , Rana Rashid Mehmood , Khan Azeem Iqbal , Khan Muhammad Azam , Ullah Atta , Naseem Misbah , Rizwana Humaira , Elshikh Mohamed S. , Rizwan Muhammad , Iqbal Rashid 
Published: November 2024

AbstractThe study was designed to validate the previously reported 34 SSR markers using 78 chilli genotypes to detect significant trait specific markers as well as superior genotypes resistant to Phytophthora capsici root rot (PcRR). In this context, the identification of germplasm with higher yield per plant (YPP) leads to hype in stress tolerance index (STI) in genotypes, Chakwal3 (11.98), Greenfire (10.14), Advanta5017 (9.94) and Chakwal4 (7.8). The identified genotypes were also found as resistant and moderately resistant due to existence of below 50% of disease incidence. Moreover, biplot showed the interrelation of STI with YPP through the formation of acute angle by their respective vectors. In the current study, the markers Hpms1172 and CAMS177 was found significant for STI. However, the marker CAMS066 was found associated with relative cell injury, CA06g27450 with disease incidence and CAMS173 with relative leaf damage. The bright bands on gel pictures of significant markers showed the association of these markers with resistant genotypes i.e. Chakwal3, Advanta-5017 and Chakwal4 as well as with a single moderately resistant genotype i.e. Greenfire. The markerstudes confirmed the phenotypic data by showing association of markers i.e. Hpms1172 and CAMS177, r with stress tolerance index. The principal coordinate analysis aligned with the results obtained from marker-assisted selection. Thus, currently practiced marker assisted selection detected high yielding genotypes in PcRR disease stress condition that will be helpful in progressing breeding programs in chilli.
Quantifying spontaneous infant movements using state-space models
Authors: Passmore E. , Kwong A. K. L. , Olsen J. E. , Eeles A. L. , Cheong J. L. Y. , Spittle A. J. , Ball G. 
Published: November 2024

AbstractOver the first few months after birth, the typical emergence of spontaneous, fidgety general movements is associated with later developmental outcomes. In contrast, the absence of fidgety movements is a core feature of several neurodevelopmental and cognitive disorders. Currently, manual assessment of early infant movement patterns is time consuming and labour intensive, limiting its wider use. Recent advances in computer vision and deep learning have led to the emergence of pose estimation techniques, computational methods designed to locate and track body points from video without specialised equipment or markers, for movement tracking. In this study, we use automated markerless tracking of infant body parts to build statistical models of early movements. Using a dataset of infant movement videos (n = 486) from 330 infants we demonstrate that infant movement can be modelled as a sequence of eight motor states using autoregressive, state-space models. Each, motor state Is characterised by specific body part movements, the expression of which varies with age and differs in infants at high-risk of poor neurodevelopmental outcome.
Efficient rare event sampling with unsupervised normalizing flows
Authors: Asghar Solomon , Pei Qing-Xiang , Volpe Giorgio , Ni Ran 
Published: November 2024

AbstractFrom physics and biology to seismology and economics, the behaviour of countless systems is determined by impactful yet unlikely transitions between metastable states known as rare events, the study of which is essential for understanding and controlling the properties of these systems. Classical computational methods to sample rare events remain prohibitively inefficient and are bottlenecks for enhanced samplers that require prior data. Here we introduce a physics-informed machine learning framework, normalizing Flow enhanced Rare Event Sampler (FlowRES), which uses unsupervised normalizing flow neural networks to enhance Monte Carlo sampling of rare events by generating high-quality non-local Monte Carlo proposals. We validated FlowRES by sampling the transition path ensembles of equilibrium and non-equilibrium systems of Brownian particles, exploring increasingly complex potentials. Beyond eliminating the requirements for prior data, FlowRES features key advantages over established samplers: no collective variables need to be defined, efficiency remains constant even as events become increasingly rare and systems with multiple routes between states can be straightforwardly simulated.
Demagnetisation fault analysis and diagnosis based on different methods in permanent magnet machines ‐ An overview
Authors: Faiz Jawad , Bazrafshan Mohammad Amin , Tabarniarami Zabihollah 
Published: November 2024

AbstractThe expansion of permanent magnet (PM) machines due to functional advantages such as power density and low losses (high efficiency) and better controllability in industrial applications has led to an increased need for research on possible faults in this type of machine and the development of effective methods to diagnose faults in different operational conditions. The performance characteristics of PM machines are strongly influenced by the PMs used in their structure. Accordingly, one of the most important PM machine faults is the demagnetisation fault which arises due to the physical, operational, and environmental conditions or their combination. This can result in damage to the functional characteristics of the machine. In this paper, the main topologies of PM machines, including the PM synchronous machines, the brushless DC motors, and the flux modulation machines, are first reviewed. Subsequently, the techniques for detecting demagnetisation faults in PM machines are then reviewed and summarised. This paper discusses the factors that cause faults in PM machines and their effects on machine performance. It also examines conventional modelling methods used to study demagnetisation faults. Finally, it presents a general structure for techniques developed for demagnetisation faults in different operating conditions (stationary and non‐stationary) and based on intelligent methods. It also compares the proposed methods and highlights their strengths and weaknesses.
Kilogauss magnetic field and jet dynamics in the quasar NRAO 530
Authors: Lisakov Mikhail , Jorstad Svetlana , Wielgus Maciek , Kravchenko Evgeniya V. , Nikonov Aleksei S. , Cho Ilje , Issaoun Sara , Algaba Juan-Carlos , Krichbaum Thomas P. , Bach Uwe , Ros Eduardo , Rottmann Helge , Sánchez Salvador , Wagner Jan , Zensus Anton 
Published: November 2024

Context. The advancement of the Event Horizon Telescope has enabled the study of relativistic jets in active galactic nuclei down to sub-parsec linear scales even at high redshift. Quasi-simultaneous multifrequency observations provide insights into the physical conditions in compact regions and allow accretion theories to be tested.
Aims. Initially, we aimed to measure the magnetic field strength close to the central supermassive black hole in NRAO 530 (1730−130) by studying the frequency-dependent opacity of the jet matter, Faraday rotation, and the spectral index in the millimeter-radio bands.
Methods. NRAO 530 was observed quasi-simultaneously at 15, 22, 43, 86, and 227 GHz at four different very long baseline interferometer (VLBI) networks. By means of imaging and model-fitting, we aligned the images, taken at different frequencies. We explored opacity along the jet and the distribution of the linearly polarized emission in it.
Results. Our findings reveal that the jet of NRAO 530 at 86 and 227 GHz is transparent down to its origin, with 70 mJy emission detected at 227 GHz potentially originating from the accretion disk. The magnetic field strength near the black hole, estimated at 5rg, is 3 × 103 − 3 × 104 G (depending on the central black hole mass). These values represent some of the highest magnetic field strengths reported for active galaxies. We also report the first ever VLBI measurement of the Faraday rotation at 43−227 GHz, which reveals rotation measure values as high as −48 000 rad/m2, consistent with higher particle density and stronger magnetic fields at the jet’s outset. The complex shape of the jet in NRAO 530 is in line with the expected behavior of a precessing jet, with a period estimated to be around 6 ± 4 years.
Active galactic nucleus time-variability analysis and its caveats
Authors: Kankkunen S. , Tornikoski M. , Hovatta T. 
Published: November 2024

Aims. In this study, we demonstrate some of the caveats in common statistical methods used for analysing astronomical variability timescales. We consider these issues specifically in the context of active galactic nuclei (AGNs) and use a more practical approach compared to mathematics literature, where the number of formulae may sometimes be overwhelming.
Methods. We conducted a thorough literature review both on the statistical properties of light-curve data, specifically in the context of sampling effects, as well as on the methods used to analyse them. We simulated a wide range of data to test some of the known issues in AGN variability analysis as well as to investigate previously unknown or undocumented caveats.
Results. We discovered problems with some commonly used methods and confirmed how challenging it is to identify timescales from observed data. We find that interpolation of a light curve with biased sampling, specifically with bias towards flaring events, affects its measured power spectral density in a different manner than those of simulated light curves. We also find that an algorithm aiming to match the probability density function of a light curve has often been used incorrectly. These new issues appear to have been mostly overlooked and not necessarily addressed before, especially in astronomy literature.
Estimating the early propagation direction of the coronal mass ejection with DIRECD during the severe event on May 8 and for the follow-up event on June 8, 2024
Authors: Jain Shantanu , Podladchikova Tatiana , Veronig Astrid M. , Chikunova Galina , Dissauer Karin , Dumbovic Mateja , Razquin Amaia 
Published: November 2024

Context. On May 8, 2024, the solar active region 13664 produced an X-class flare, several M-class flares, and multiple coronal mass ejections (CMEs) directed towards Earth. The initial CME resulted in coronal dimmings, which are characterized by localized reductions in extreme-ultraviolet (EUV) emissions and are indicative of mass loss and expansion during the eruption. On June 8, 2024, after one solar rotation, the same active region produced another eruptive M-class flare that was followed by coronal dimmings that were observed by the Solar Dynamics Observatory (SDO) and the Solar Terrestrial Relations Observatory (STEREO) spacecraft.
Aims. We analyzed the early CME evolution and propagation direction from the expansion of the coronal dimming observed low in the corona using the method called dimming inferred estimation of the CME direction (DIRECD).
Methods. DIRECD derived the key parameters of the early CME propagation from the expansion behavior of the associated coronal dimming at the end of its impulsive phase by generating a 3D CME cone model whose orthogonal projection on the solar sphere matches the dimming geometry. To validate the resulting 3D CME cone, we compared the CME properties derived in the low corona with white-light coronagraph data.
Results. Using DIRECD, we find that the CME on May 8, 2024 expands close to radially, with an inclination angle of 7.7°, an angular width of 70°, and a cone height of 0.81 Rsun, which was derived at the end of the impulsive dimming phase, and for which the CME showed connections to the dimming and still left footprints in the low corona. It was inclined 7.6° north in the meridional plane and 1.1° east in the equatorial plane. The CME on June 8, 2024, after one solar rotation, was inclined by 15.7° from the radial direction, had an angular width of 81°, and had a cone height of 0.89 Rsun. The CME was inclined 6.9° south in the meridional plane and 14.9° west in the equatorial plane. A validation with white-light coronagraph data confirmed the accuracy of the 3D cone by matching the CME characteristics and projections with STEREO-A COR2 observations.
Conclusions. Our study demonstrates that by tracking low coronal signatures such as the coronal dimming expansion in 2D for the May and June 2024 CMEs, we can estimate the 3D CME direction early in the CME evolution. This provides early lead times for mitigating adverse space weather impacts.