bluuebunny/crossref_metadata_2025 huggingface dataset:
Negotiating the norms of an international science: standardization work at the International Geological Congress, 1878–1891
Authors: Mougey Thomas
Published: September 2023

In the second half of the nineteenth century, geologists created the International Geological Congress (IGC) to achieve the methodological and terminological uniformity that they thought their science lacked. Their desire to standardize their practice and their use of the conference to do so was neither new nor unique. Although late nineteenth-century international conferences have been recognized as important arenas of standardization, relatively little is known of the ways in which conferences organized standardization negotiations. This article aims to fill this gap by exploring how the IGC practically and socially organized standardization work. It appears that the session hall was not the sole and not even the main stage of geological standard-setting. The standardization process was also enacted through comparative study and informal exchanges that regular visits to purpose-built comparative geological exhibitions made possible. Relying on a sophisticated apparatus of commissions and subcommittees, the IGC also socially organized standards negotiation beyond the space and time of the triennial sessions. By tracing the material, spatial and social practices engineered through the IGC to serve geological standardization, this article unboxes the conference process and in so doing enriches our understanding of the period's wave of standardization.
A fluke encounter: first record of the blue whale (Balaenoptera musculus) within the central North Sea, United Kingdom
Authors: Lavallin Edward , Øien Nils , Sears Richard
Published: September 2023

Despite holding the accolade as the largest animal ever to live on planet earth and ubiquitously inhabiting the world's major oceans, an acute paucity of information surrounds the geographical distribution and migration phenology of the endangered blue whale (Balaenoptera musculus) in the northeast Atlantic. Current migration and distribution information derived from robust scientific studies is required to ensure the formulation and implementation of successful conservation measures with a vision to support the ongoing recovery of the northeast Atlantic population. At 10:21 (UTC) on the 9th of November 2020, two blue whales were observed at position 55°13.99′N, 01°13.62′W, 18 km off the coast of the UK in the central North Sea just north of Newcastle at a water depth of 76 m. This is the first paper that has confirmed an account of live blue whales frequenting shallow waters of the central North Sea and represents a new area of occurrence within the accepted range of the northeast Atlantic population, an area in which sightings are extremely rare and may provide insight into the intricacies of migration routes and behaviour.
Reasoning with reasons: Lewis on common knowledge
Authors: Vromen Huub
Published: September 2023

David Lewis is widely regarded as the philosopher who introduced the concept of common knowledge. His account of common knowledge differs greatly from most later accounts in philosophy and economy, with the central notion of his theory being ‘having reason to believe’ rather than ‘knowledge’. Unfortunately, Lewis’s account is rather informal, and the argument has a few gaps. This paper assesses two major attempts to formalise Lewis’s account and argues that these formalisations are missing a crucial aspect of this account. Therefore, a new reconstruction is proposed, which explicitly discusses ‘reasons’ and uses a logic inspired by justification logic.
Re-assessing the role of peri-operative nutritional therapy in patients with pancreatic cancer undergoing surgery: a narrative review
Authors: Bouloubasi Zoi , Karayiannis Dimitrios , Pafili Zoe , Almperti Avra , Nikolakopoulou Konstantina , Lakiotis Grigoris , Stylianidis George , Vougas Vasilios
Published: September 2023

Pancreatic cancer is the most common medical condition that requires pancreatic resection. Over the last three decades, significant improvements have been made in the conditions and procedures related to pancreatic surgery, resulting in mortality rates lower than 5%. However, it is important to note that the morbidity in pancreatic surgery remains r latively high, with a percentage range of 30–60%. Pre-operative malnutrition is considered to be an independent risk factor for post-operative complications in pancreatic surgery, such as impaired wound healing, higher infection rates, prolonged hospital stay, hospital readmission, poor prognosis, and increased morbidity and mortality. Regarding the post-operative period, it is crucial to provide the best possible management of gastrointestinal dysfunction and to handle the consequences of alterations in food digestion and nutrient absorption for those undergoing pancreatic surgery. The European Society for Clinical Nutrition and Metabolism (ESPEN) suggests that early oral feeding should be the preferred way to initiate nourishing surgical patients as it is associated with lower rates of complications. However, there is ongoing debate about the optimal post-operative feeding approach. Several studies have shown that enteral nutrition is associated with a shorter time to recovery, superior clinical outcomes and biomarkers. On the other hand, recent data suggest that nutritional goals are better achieved with parenteral feeding, either exclusively or as a supplement. The current review highlights recommendations from existing evidence, including nutritional screening and assessment and pre/post-operative nutrition support fundamentals to improve patient outcomes. Key areas for improvement and opportunities to enhance guideline implementation are also highlighted.
The Prevalence of Suicidal Behavior in Autism Spectrum Disorder
Authors: Huntjens Anne , Landlust Annemiek , Wissenburg Sophie , van der Gaag Mark
Published: September 2023

Abstract: Background: Suicidal ideation (SI) and suicide attempts (SA) are common in autistic individuals, but prevalence rates have not yet been estimated with meta-analysis. Aims: This meta-analysis aims to estimate SI and SA prevalence rates in autistic individuals and identify subgroup differences based on sample characteristics and study quality. Methods: A systematic search identified 52 studies with 88,509 autistic participants reporting SI and SA. Pooled prevalence estimates were calculated using a random-effects model. Results: Pooled prevalence estimates of lifetime SI and SA were 37.2% [95% CI 25.3–50.8] and 15.3% [95% CI 9.5–23.6], respectively. For 12-month prevalence, this was 25.4% [95% CI 19.0–33.2] and 14.1% [95% CI 7.4–25.2], respectively. Subgroup analyses revealed significant differences based on age (SI), region (SI), data collection (SI), measurement scales used to define autism and suicidality (SA), and representation of the study sample (SI and SA). Heterogeneity measures were high for all outcomes ( I2 = 60.3–99.1%). Limitations: The heterogeneity of the included studies may limit the generalizability of our findings. Conclusion: The high rates of suicidal problems in autistic individuals call for a systematic evaluation of suicidality in clinical practice and adequate therapeutic interventions to improve this condition.
Thermal Moonquake Characterization and Cataloging Using Frequency‐Based Algorithms and Stochastic Gradient Descent
Authors: Civilini F. , Weber R. , Husker A.
Published: September 2023

Thermal moonquakes are recurring seismic signals detected on the lunar surface that are temporally correlated with the lunar day‐night cycle, although their precise mechanism is not known. The Lunar Seismic Profiling Experiment (LSPE) was a deployment of four geophones during the Apollo 17 mission to characterize the near‐surface structure of the landing site using explosive shots. The array was reactivated in passive recording mode several times after the mission was completed and recorded thousands of thermal moonquakes. In this study, we expand on an initial detection catalog and determine waveform parameters and source information for the seismic signals. We used a spectrogram‐based approach to obtain fine‐tuned arrival times, quantify the envelope length using emergence, and compute peak‐ground‐velocity. We obtain the incident azimuth direction by applying stochastic gradient descent to a travel‐time misfit equation. We found that thermal moonquakes are split into two main classes: (a) impulsive, high‐amplitude events that are produced by the lunar module descent vehicle located east of the LSPE array in response to rapid temperature transitions during sunrise and sunset and (b) emergent events, that are natural responses to incident sunlight whose duration is directly linked to the temperature of the regolith. We hypothesize that the correlation between temperature and emergence could be due to changes in regolith scattering or higher energy daytime events occurring further away.
Machine Learning‐Based New Earthquake Catalog Illuminates On‐Fault and Off‐Fault Seismicity Patterns at the Discovery Transform Fault, East Pacific Rise
Authors: Gong Jianhua , Fan Wenyuan , Parnell‐Turner Ross
Published: September 2023

Oceanic transform faults connect spreading centers and are imprinted with previous tectonic events. However, their tectonic interactions are not well understood due to limited observations. The Discovery transform fault system at 4°S, East Pacific Rise (EPR), represents a young transform system, offering a unique opportunity to study the interplay between faulting and other tectonic events at an early phases of an oceanic transform system. Discovery regularly hosts M5–6 characteristic earthquakes, and the seafloor north of Discovery includes a 35 km‐long rift zone that records a complex history of rifting, faulting and volcanism, suggesting that the transform faults likely interact with regional tectonic activity. We apply a machine‐learning enabled workflow to locate 21,391 earthquakes recorded during a 1‐year ocean bottom seismometer experiment in 2008. Our results indicate that seismicity on the western Discovery fault is separated into seven patches with distinct aseismic and seismic slip modes. Additionally, we observe a patch of off‐fault seismicity near where seafloor abyssal hills intersect the rift zone. This seismicity may have been caused by varying opening rates as spreading rate decreases from north to south in the rift zone. Our findings suggest that the Discovery system is still evolving, and that system equilibrium has not been reached between rifting and faulting. These results reflect the complex yet rarely observed interactions between fault slip, plate rotation, and rifting which are likely ubiquitous at oceanic transform systems.
Assessing the Effects of a Minor CIR‐HSS Geomagnetic Storm on the Brazilian Low‐Latitude Ionosphere: Ground and Space‐Based Observations
Authors: Chingarandi F. S. , Candido C. M. N. , Becker‐Guedes F. , Jonah O. F. , Moraes‐Santos S. P. , Klausner V. , Taiwo O. O.
Published: September 2023

This paper investigates the effects of a minor G1 Co‐rotating Interaction Region (CIR)/High‐Speed Stream (HSS)‐driven geomagnetic storm that occurred on (13–14 October 2018), during deep solar minimum. We used simultaneous observations from multiple instruments, namely; ground‐based Global Navigation Satellite Systems (GNSS) receivers, a Digisonde, ground magnetometers, and space‐based observations from the National Aeronautics and Space Administration Global‐scale Observations of Limb and Disk (GOLD) and SWARM missions. This study presents a detailed picture of the low‐latitude ionosphere response over the Brazilian sector during a minor storm. Our results showed that the minor CIR/HSS‐driven storm caused a positive ionospheric storm of over ∼20 TECU in magnitude. For the first time, periodic post‐sunset irregularities and Equatorial Plasma Bubbles, equatorial plasma bubbles, were analyzed using GOLD FUV OI 135.6 nm emission, Total Electron Content (TEC) maps, Rate of TEC index, ROTI, and TEC gradients. Fluctuations in the interplanetary magnetic field Bz and changes in the thermospheric column density ratio (∑O/N2) are discussed as the main sources of ionospheric changes during the storm. This paper highlights the importance of monitoring and understanding the impact of Sun‐Earth interactions and provides insight into the behavior of the low‐latitude ionosphere during minor geomagnetic storms.
Probabilistic Solar Proxy Forecasting With Neural Network Ensembles
Authors: Daniell Joshua D. , Mehta Piyush M.
Published: September 2023

Space weather indices are used commonly to drive forecasts of thermosphere density, which affects objects in low‐Earth orbit (LEO) through atmospheric drag. One commonly used space weather proxy, F10.7cm, correlates well with solar extreme ultra‐violet (EUV) energy deposition into the thermosphere. Currently, the USAF contracts Space Environment Technologies (SET), which uses a linear algorithm to forecast F10.7cm. In this work, we introduce methods using neural network ensembles with multi‐layer perceptrons (MLPs) and long‐short term memory (LSTMs) to improve on the SET predictions. We make predictions only from historical F10.7cm values. We investigate data manipulation methods (backwards averaging and lookback) as well as multi step and dynamic forecasting. This work shows an improvement over the popular persistence and the operational SET model when using ensemble methods. The best models found in this work are ensemble approaches using multi step or a combination of multi step and dynamic predictions. Nearly all approaches offer an improvement, with the best models improving between 48% and 59% on relative MSE with respect to persistence. Other relative error metrics were shown to improve greatly when ensembles methods were used. We were also able to leverage the ensemble approach to provide a distribution of predicted values; allowing an investigation into forecast uncertainty. Our work found models that produced less biased predictions at elevated and high solar activity levels. Uncertainty was also investigated through the use of a calibration error score metric (CES), our best ensemble reached similar CES as other work.
Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk
Authors: Aslam M. Muaaz , Fan Kang-Hsien , Lawrence Elizabeth , Bedison Margaret Anne , Snitz Beth E. , DeKosky Steven T. , Lopez Oscar L. , Feingold Eleanor , Kamboh M. Ilyas
Published: September 2023

The APOE 2/3/4 polymorphism is the greatest genetic risk factor for Alzheimer’s disease (AD). This polymorphism is also associated with variation in plasma ApoE level; while APOE*4 lowers, APOE*2 increases ApoE level. Lower plasma ApoE level has also been suggested to be a risk factor for incident dementia. To our knowledge, no large genome-wide association study (GWAS) has been reported on plasma ApoE level. This study aimed to identify new genetic variants affecting plasma ApoE level as well as to test if baseline ApoE level is associated with cognitive function and incident dementia in a longitudinally followed cohort of the Ginkgo Evaluation of Memory (GEM) study. Baseline plasma ApoE concentration was measured in 3031 participants (95.4% European Americans (EAs)). GWAS analysis was performed on 2580 self-identified EAs where both genotype and plasma ApoE data were available. Lower ApoE concentration was associated with worse cognitive function, but not with incident dementia. As expected, the risk for AD increased from E2/2 through to E4/4 genotypes (P for trend = 4.8E-75). In addition to confirming the expected and opposite associations of APOE*2 (P = 4.73E-79) and APOE*4 (P = 8.73E-12) with ApoE level, GWAS analysis revealed nine additional independent signals in the APOE region, and together they explained about 22% of the variance in plasma ApoE level. We also identified seven new loci on chromosomes 1, 4, 5, 7, 11, 12 and 20 (P range = 5.49E-08 to 5.36E-10) that explained about 9% of the variance in ApoE level. Plasma ApoE level-associated independent variants, especially in the APOE region, were also associated with AD risk and amyloid deposition in the brain, indicating that genetically determined ApoE level variation may be a risk factor for developing AD. These results improve our understanding of the genetic determinants of plasma ApoE level and their potential value in affecting AD risk.
Dlk2 interacts with Syap1 to activate Akt signaling pathway during osteoclast formation
Authors: Chen Xinwei , Chen Xuzhuo , Chao Rui , Wang Yexin , Mao Yi , Fan Baoting , Zhang Yaosheng , Xu Weifeng , Qin An , Zhang Shanyong
Published: September 2023

Excessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the AktSer473, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.
Fine-scale collective movements reveal present, past and future dynamics of a multilevel society in Przewalski’s horses
Authors: Ozogány Katalin , Kerekes Viola , Fülöp Attila , Barta Zoltán , Nagy Máté
Published: September 2023

Studying animal societies needs detailed observation of many individuals, but technological advances offer new opportunities in this field. Here, we present a state-of-the-art drone observation of a multilevel herd of Przewalski’s horses, consisting of harems (one-male, multifemale groups). We track, in high spatio-temporal resolution, the movements of 238 individually identified horses on drone videos, and combine movement analyses with demographic data from two decades of population monitoring. Analysis of collective movements reveals how the structure of the herd’s social network is related to kinship and familiarity of individuals. The network centrality of harems is related to their age and how long the harem stallions have kept harems previously. Harems of genetically related stallions are closer to each other in the network, and female exchange is more frequent between closer harems. High movement similarity of females from different harems predicts becoming harem mates in the future. Our results show that only a few minutes of fine-scale movement tracking combined with high throughput data driven analysis can reveal the structure of a society, reconstruct past group dynamics and predict future ones.
Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm
Authors: Grahn Elena , Kaufmann Svenja V. , Askarova Malika , Ninov Momchil , Welp Luisa M. , Berger Thomas K. , Urlaub Henning , Kaupp U.Benjamin
Published: September 2023

The reaction of CO2 with H2O to form bicarbonate (HCO3−) and H+ controls sperm motility and fertilization via HCO3−-stimulated cAMP synthesis. A complex network of signaling proteins participates in this reaction. Here, we identify key players that regulate intracellular pH (pHi) and HCO3− in human sperm by quantitative mass spectrometry (MS) and kinetic patch-clamp fluorometry. The resting pHi is set by amiloride-sensitive Na+/H+ exchange. The sperm-specific putative Na+/H+ exchanger SLC9C1, unlike its sea urchin homologue, is not gated by voltage or cAMP. Transporters and channels implied in HCO3− transport are not detected, and may be present at copy numbers < 10 molecules/sperm cell. Instead, HCO3− is produced by diffusion of CO2 into cells and readjustment of the CO2/HCO3−/H+ equilibrium. The proton channel Hv1 may serve as a unidirectional valve that blunts the acidification ensuing from HCO3− synthesis. This work provides a new framework for the study of male infertility.
A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury
Authors: Calafiore Marco , Fu Ya-Yuan , Vinci Paola , Arnhold Viktor , Chang Winston Y. , Jansen Suze A. , Egorova Anastasiya , Takashima Shuichiro , Kuttiyara Jason , Ito Takahiro , Serody Jonathan , Nakae Susumu , Turnquist Heth , van Es Johan , Clevers Hans , Lindemans Caroline A. , Blazar Bruce R. , Hanash Alan M.
Published: September 2023

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.
Programmable RNA detection with CRISPR-Cas12a
Authors: Rananaware Santosh R. , Vesco Emma K. , Shoemaker Grace M. , Anekar Swapnil S. , Sandoval Luke Samuel W. , Meister Katelyn S. , Macaluso Nicolas C. , Nguyen Long T. , Jain Piyush K.
Published: September 2023

Cas12a, a CRISPR-associated protein complex, has an inherent ability to cleave DNA substrates and is utilized in diagnostic tools to identify DNA molecules. We demonstrate that multiple orthologs of Cas12a activate trans-cleavage in the presence of split activators. Specifically, the PAM-distal region of the crRNA recognizes RNA targets provided that the PAM-proximal seed region has a DNA target. Our method, Split Activator for Highly Accessible RNA Analysis (SAHARA), detects picomolar concentrations of RNA without sample amplification, reverse-transcription, or strand-displacement by simply supplying a short DNA sequence complementary to the seed region. Beyond RNA detection, SAHARA outperforms wild-type CRISPR-Cas12a in specificity towards point-mutations and can detect multiple RNA and DNA targets in pooled crRNA/Cas12a arrays via distinct PAM-proximal seed DNAs. In conclusion, SAHARA is a simple, yet powerful nucleic acid detection platform based on Cas12a that can be applied in a multiplexed fashion and potentially be expanded to other CRISPR-Cas enzymes.
The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases
Authors: Ghaddar Nagham , Corda Yves , Luciano Pierre , Galli Martina , Doksani Ylli , Géli Vincent
Published: September 2023

Homologous recombination factors play a crucial role in protecting nascent DNA during DNA replication, but the role of chromatin in this process is largely unknown. Here, we used the bacterial Tus/Ter barrier known to induce a site-specific replication fork stalling in S. cerevisiae. We report that the Set1C subunit Spp1 is recruited behind the stalled replication fork independently of its interaction with Set1. Spp1 chromatin recruitment depends on the interaction of its PHD domain with H3K4me3 parental histones deposited behind the stalled fork. Its recruitment prevents the accumulation of ssDNA at the stalled fork by restricting the access of Exo1. We further show that deleting SPP1 increases the mutation rate upstream of the barrier favoring the accumulation of microdeletions. Finally, we report that Spp1 protects nascent DNA at the Tus/Ter stalled replication fork. We propose that Spp1 limits the remodeling of the fork, which ultimately limits nascent DNA availability to nucleases.
Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia
Authors: Jash Sukanta , Banerjee Sayani , Cheng Shibin , Wang Bin , Qiu Chenxi , Kondo Asami , Ernerudh Jan , Zhou Xiao Zhen , Lu Kun Ping , Sharma Surendra
Published: September 2023

Preeclampsia (PE) is the leading cause of maternal and fetal mortality globally and may trigger dementia later in life in mothers and their offspring. However, the etiological drivers remain elusive. Cis P-tau is an early etiological driver and blood biomarker in pre-clinical Alzheimer’s and after vascular or traumatic brain injury, which can be targeted by stereo-specific antibody, with clinical trials ongoing. Here we find significant cis P-tau in the placenta and serum of PE patients, and in primary human trophoblasts exposed to hypoxia or sera from PE patients due to Pin1 inactivation. Depletion of cis P-tau from PE patient sera by the antibody prevents their ability to disrupt trophoblast invasion and endovascular activity and to cause the PE-like pathological and clinical features in pregnant humanized tau mice. Our studies uncover that cis P-tau is a central circulating etiological driver and its stereo-specific antibody is valuable for early PE diagnosis and treatment.
MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention
Authors: Qiu Bin , Lawan Ahmed , Xirouchaki Chrysovalantou E. , Yi Jae-Sung , Robert Marie , Zhang Lei , Brown Wendy , Fernández-Hernando Carlos , Yang Xiaoyong , Tiganis Tony , Bennett Anton M.
Published: September 2023

Nonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed male mice. The focus of this work is to investigate whether and how MKP1 is involved in the development of NASH. Under NASH conditions increased oxidative stress, induces MKP1 expression leading to nuclear p38 MAPK dephosphorylation and decreases liver kinase B1 (LKB1) phosphorylation at a site required to promote LKB1 nuclear exit. Hepatic deletion of MKP1 in NASH diet fed male mice releases nuclear LKB1 into the cytoplasm to activate AMPKα and prevents hepatocellular death, inflammation and NASH. Hence, nuclear-localized MKP1-p38 MAPK-LKB1 signaling is required to suppress AMPKα which triggers hepatocyte death and the development of NASH.
The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
Authors: Velasco-Carneros Lorea , Cuéllar Jorge , Dublang Leire , Santiago César , Maréchal Jean-Didier , Martín-Benito Jaime , Maestro Moisés , Fernández-Higuero José Ángel , Orozco Natalia , Moro Fernando , Valpuesta José María , Muga Arturo
Published: September 2023

J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.
Cryo-EM structure of a bacteriophage M13 mini variant
Authors: Jia Qi , Xiang Ye
Published: September 2023

Filamentous bacteriophages package their circular, single stranded DNA genome with the major coat protein pVIII and the minor coat proteins pIII, pVII, pVI, and pIX. Here, we report the cryo-EM structure of a ~500 Å long bacteriophage M13 mini variant. The distal ends of the mini phage are sealed by two cap-like complexes composed of the minor coat proteins. The top cap complex consists of pVII and pIX, both exhibiting a single helix structure. Arg33 of pVII and Glu29 of pIX, located on the inner surface of the cap, play a key role in recognizing the genome packaging signal. The bottom cap complex is formed by the hook-like structures of pIII and pVI, arranged in helix barrels. Most of the inner ssDNA genome adopts a double helix structure with a similar pitch to that of the A-form double-stranded DNA. These findings provide insights into the assembly of filamentous bacteriophages.
Topological magneto-optical effect from skyrmion lattice
Authors: Kato Yoshihiro D. , Okamura Yoshihiro , Hirschberger Max , Tokura Yoshinori , Takahashi Youtarou
Published: September 2023

The magnetic skyrmion is a spin-swirling topological object characterized by its nontrivial winding number, holding potential for next-generation spintronic devices. While optical readout has become increasingly important towards the high integration and ultrafast operation of those devices, the optical response of skyrmions has remained elusive. Here, we show the magneto-optical Kerr effect (MOKE) induced by the skyrmion formation, i.e., topological MOKE, in Gd2PdSi3. The significantly enhanced optical rotation found in the skyrmion phase demonstrates the emergence of topological MOKE, exemplifying the light-skyrmion interaction arising from the emergent gauge field. This gauge field in momentum space causes a dramatic reconstruction of the electronic band structure, giving rise to magneto-optical activity ranging up to the sub-eV region. The present findings pave a way for photonic technology based on skyrmionics.
Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A
Authors: Weng Chen , Gu Anniya , Zhang Shanshan , Lu Leina , Ke Luxin , Gao Peidong , Liu Xiaoxiao , Wang Yuntong , Hu Peinan , Plummer Dylan , MacDonald Elise , Zhang Saixian , Xi Jiajia , Lai Sisi , Leskov Konstantin , Yuan Kyle , Jin Fulai , Li Yan
Published: September 2023

Broad heterogeneity in pancreatic β-cell function and morphology has been widely reported. However, determining which components of this cellular heterogeneity serve a diabetes-relevant function remains challenging. Here, we integrate single-cell transcriptome, single-nuclei chromatin accessibility, and cell-type specific 3D genome profiles from human islets and identify Type II Diabetes (T2D)-associated β-cell heterogeneity at both transcriptomic and epigenomic levels. We develop a computational method to explicitly dissect the intra-donor and inter-donor heterogeneity between single β-cells, which reflect distinct mechanisms of T2D pathogenesis. Integrative transcriptomic and epigenomic analysis identifies HNF1A as a principal driver of intra-donor heterogeneity between β-cells from the same donors; HNF1A expression is also reduced in β-cells from T2D donors. Interestingly, HNF1A activity in single β-cells is significantly associated with lower Na+ currents and we nominate a HNF1A target, FXYD2, as the primary mitigator. Our study demonstrates the value of investigating disease-associated single-cell heterogeneity and provides new insights into the pathogenesis of T2D.
Combined SPT and FCS methods reveal a mechanism of RNAP II oversampling in cell nuclei
Authors: Fournier Marie , Leclerc Pierre , Leray Aymeric , Champelovier Dorian , Agbazahou Florence , Dahmani Fatima , Bidaux Gabriel , Furlan Alessandro , Héliot Laurent
Published: September 2023

Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining single particle tracking (SPT) and fluorescence correlation spectroscopy (FCS) techniques, to take advantage of their different sensitivities in order to analyze together slow and fast molecular movements. Thanks to calibrated samples, we developed a benchmark for quantitative analysis of molecular dynamics, to eliminate the main potential instrumental biases. We applied this workflow to study the diffusion of RPB1, the catalytic subunit of RNAP II. By a cross-analysis of FCS and SPT, we could highlight different RPB1 motility states and identifyed a stationary state, a slow diffusion state, and two different modes of subdiffusion. Interestingly, our analysis also unveiled the oversampling by RPB1 of nuclear subdomains. Based on these data, we propose a novel model of spatio-temporal transcription regulation. Altogether, our results highlight the importance of combining microscopy approaches at different time scales to get a full insight into the real complexity of molecular kinetics in cells.
Impact of hand osteoarthritis in women on maximal forces in six different grasp types
Authors: Gracia-Ibáñez Verónica , Jarque-Bou Néstor J. , Bayarri-Porcar Vicente , Roda-Sales Alba , Granell Pablo , Vergara Margarita , Sancho-Bru Joaquín L.
Published: September 2023

This work aims to: (1) Provide maximal hand force data on six different grasp types for healthy subjects; (2) detect grasp types with maximal force significantly affected by hand osteoarthritis (HOA) in women; (3) look for predictors to detect HOA from the maximal forces using discriminant analyses. Thirty-three healthy subjects (37 ± 17 years, 17 women, 16 men) and 30 HOA patients (72 ± 9 years, all women) participated in the experiment. Participants were asked to exert their maximal force while performing six different grasp types 3 times. Two MANOVAs were conducted to detect if force depended on gender in healthy participants and if force significantly diminished in women with HOA. Finally, a linear discriminant analysis for detecting HOA was performed using forces of the grasp types that were significantly affected by HOA. Gender-disaggregated statistics are provided for healthy participants. Significant differences are obtained for all grasp types per gender. The women with HOA exerted significantly lower force values (p < 0.001) for all the grasp types than healthy ones. The discriminant analysis revealed that oblique grasp was the most significant one for detecting HOA. A discrimination equation was obtained with a specificity of 88.2% and a sensitivity of 83.3%. This work provides grip force data on six grasp types for healthy participants and for women with HOA. HOA women present reduced strength in all grasps due to pathology. Three of these grasps are a novelty. Oblique grasp strength may suffice to discriminate a patient with HOA, which might help non-invasive HOA detection.
Video action recognition collaborative learning with dynamics via PSO-ConvNet Transformer
Authors: Nguyen Huu Phong , Ribeiro Bernardete
Published: September 2023

Recognizing human actions in video sequences, known as Human Action Recognition (HAR), is a challenging task in pattern recognition. While Convolutional Neural Networks (ConvNets) have shown remarkable success in image recognition, they are not always directly applicable to HAR, as temporal features are critical for accurate classification. In this paper, we propose a novel dynamic PSO-ConvNet model for learning actions in videos, building on our recent work in image recognition. Our approach leverages a framework where the weight vector of each neural network represents the position of a particle in phase space, and particles share their current weight vectors and gradient estimates of the Loss function. To extend our approach to video, we integrate ConvNets with state-of-the-art temporal methods such as Transformer and Recurrent Neural Networks. Our experimental results on the UCF-101 dataset demonstrate substantial improvements of up to 9% in accuracy, which confirms the effectiveness of our proposed method. In addition, we conducted experiments on larger and more variety of datasets including Kinetics-400 and HMDB-51 and obtained preference for Collaborative Learning in comparison with Non-Collaborative Learning (Individual Learning). Overall, our dynamic PSO-ConvNet model provides a promising direction for improving HAR by better capturing the spatio-temporal dynamics of human actions in videos. The code is available athttps://github.com/leonlha/Video-Action-Recognition-Collaborative-Learning-with-Dynamics-via-PSO-ConvNet-Transformer.
Identification of non-ischaemic fibrosis in male veteran endurance athletes, mechanisms and association with premature ventricular beats
Authors: Farooq Maryum , Brown Louise A. E. , Fitzpatrick Andrew , Broadbent David A. , Wahab Ali , Klassen Joel R. L. , Farley Jonathan , Saunderson Christopher E. D. , Das Arka , Craven Thomas , Dall’Armellina Erica , Levelt Eylem , Xue Hui , Kellman Peter , Greenwood John P. , Plein Sven , Swoboda Peter P.
Published: September 2023

Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p < 0.0001) and lower rest myocardial blood flow (MBF, 0.5 ± 0.1 vs. 0.6 ± 0.1 ml/g/min, p < 0.0001). On 24-h ECG, athletes with fibrosis had greater burden of premature ventricular beats (0.3 ± 0.6 vs. 0.05 ± 0.2%, p = 0.03), with higher prevalence of ventricular couplets and triplets (33 vs. 8%, p = 0.02). In veteran endurance athletes, myocardial fibrosis is common and associated with an increased burden of ventricular ectopy. Possible mechanisms include inflammation and blood pressure. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.
68Ga-bisphosphonates for the imaging of extraosseous calcification by positron emission tomography
Authors: Keeling George P. , Baark Friedrich , Katsamenis Orestis L. , Xue Jing , Blower Philip J. , Bertazzo Sergio , T. M. de Rosales Rafael
Published: September 2023

Radiolabelled bisphosphonates (BPs) and [18F]NaF (18F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [18F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging. These two radiotracers bind calcium mineral deposits via different mechanisms, with BPs chelating to calcium ions and thus being non-selective, and [18F]NaF being selective for hydroxyapatite (HAp) which is the main component of bone mineral. Considering that the composition of EC has been reported to include a diverse range of non-HAp calcium minerals, we hypothesised that BPs may be more sensitive for imaging EC due to their ability to bind to both HAp and non-HAp deposits. We report a comparison between the 68Ga-labelled BP tracer [68Ga]Ga-THP-Pam and [18F]NaF for PET imaging in a rat model of EC that develops macro- and microcalcifications in several organs. Macrocalcifications were identified using preclinical computed tomography (CT) and microcalcifications were identified using µCT-based 3D X-ray histology (XRH) on isolated organs ex vivo. The morphological and mineral analysis of individual calcified deposits was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). PET imaging and ex vivo analysis results demonstrated that while both radiotracers behave similarly for bone imaging, the BP-based radiotracer [68Ga]Ga-THP-Pam was able to detect EC more sensitively in several organs in which the mineral composition departs from that of HAp. Our results strongly suggest that BP-based PET radiotracers such as [68Ga]Ga-THP-Pam may have a particular advantage for the sensitive imaging and early detection of EC by being able to detect a wider array of relevant calcium minerals in vivo than [18F]NaF, and should be evaluated clinically for this purpose.
Microplastics influence on herbicides removal and biosurfactants production by a Bacillus sp. strain active against Fusarium culmorum
Authors: Walaszczyk Aleksandra , Jasińska Anna , Bernat Przemysław , Płaza Grażyna , Paraszkiewicz Katarzyna
Published: September 2023

The amounts of anthropogenic pollutants, e.g., microplastics (MPs) and pesticides, in terrestrial and aquatic ecosystems have been increasing. The aim of this study was to assess the influence of MPs on the removal of herbicides (metolachlor, MET; 2,4-dichlorophenoxyacetic acid, 2,4-D) and the production of biosurfactants (surfactin and iturin) by Bacillus sp. Kol L6 active against Fusarium culmorum. The results showed that Kol L6 eliminated 40–55% MET and 2,4-D from liquid cultures, but this process was inhibited in the presence of MPs. Although the pollutants did not strongly limit the production of surfactin, iturin secretion was found to decrease by more than 70% in the presence of all three pollutants. Interestingly, the strongest modification in the profile of iturin homologues was calculated for the cultures containing MET + MP and 2,4-D + MET + MP. The bacteria significantly limited the growth of the phytopathogenic F. culmorum DSM1094F in the presence of individual pollutants and their two-component mixtures. However, in the presence of all three tested pollutants, the growth of the fungus was limited only partially (by no more than 40%). The presented results are a starting point for further research on bacteria-fungi-plants interactions in the soil environment in the presence of multiple pollutants.
SCH23390 and a humanized anti-cocaine mAb decrease the latency to cocaine-induced reinstatement of lever pressing behavior in rats that self-administer cocaine
Authors: Zinani Dakota B. , Desai Jhanvi N. , Norman Andrew B.
Published: September 2023

In rats that self-administer cocaine, the latency to the reinstatement of lever pressing behavior induced by a single dose of cocaine is due to the time taken for cocaine levels to fall to the satiety threshold. The D1 dopamine receptor antagonist SCH23390, and the recombinant humanized anti-cocaine mAb h2E2 increase the cocaine satiety threshold and would be expected to alter the latency to reinstatement. Male rats acquired cocaine self-administration behavior on an FR1 schedule. These rats received a single injection of cocaine (12 µmol/kg i.v.) after an i.v. injection of SCH23390 or an infusion of h2E2 or vehicle. The latency to, and the duration of, lever pressing was measured but the presses had no consequence. SCH23390 decreased the latency to lever pressing consistent with dose-dependent increases in satiety threshold. The duration of lever pressing behavior was inversely proportional to the SCH23390 dose suggesting that SCH23390 also increased the cocaine compulsion zone. The mAb h2E2 also produced a similar decrease in latency to responding that gradually reversed over 2 weeks. SCH23390 and h2E2 had an additive effect on the decreased latency to cocaine-induced lever pressing. The single cocaine dose reinstatement paradigm within the context of the compulsion zone theory is a useful pharmacological bioassay system to explore potential pharmacotherapies for relapse prevention in cocaine use disorder.
Assessing the impact of turbulent kinetic energy boundary conditions on turbulent flow simulations using computational fluid dynamics
Authors: Jung Eui Cheol , Lee Gyu-Han , Shim Eun Bo , Ha Hojin
Published: September 2023

Computational fluid dynamics has been widely used to study hemodynamics, but accurately determining boundary conditions for turbulent blood flow remains challenging. This study aims to investigate the effect of patient-specific turbulence boundary conditions on the accuracy of turbulent flow simulation. Using a stenosis model with 50% severity in diameter, the post-stenosis turbulence flow region was simulated with different planes to obtain inlet boundary conditions and simulate downstream flows. The errors of simulated flow fields obtained with turbulence kinetic energy (TKE) boundary data and arbitrary turbulence intensity were compared. Additionally, the study tested various TKE data resolutions and noise levels to simulate experimental environments. The mean absolute error of velocity and TKE was investigated with various turbulence intensities and TKE mapping. While voxel size and signal-to-noise ratio of the TKE data affected the results, simulation with SNR > 5 and voxel size < 10% resulted in better accuracy than simulations with turbulence intensities. The simulation with appropriate TKE boundary data resulted in a more accurate velocity and turbulence field than those with arbitrary turbulence intensity boundary conditions. The study demonstrated the potential improvement of turbulent blood flow simulation with patient-specific turbulence boundary conditions, which can be obtained from recent measurement techniques.
OCT-based deep-learning models for the identification of retinal key signs
Authors: Leandro Inferrera , Lorenzo Borsatti , Aleksandar Miladinovic , Dario Marangoni , Rosa Giglio , Agostino Accardo , Daniele Tognetto
Published: September 2023

A new system based on binary Deep Learning (DL) convolutional neural networks has been developed to recognize specific retinal abnormality signs on Optical Coherence Tomography (OCT) images useful for clinical practice. Images from the local hospital database were retrospectively selected from 2017 to 2022. Images were labeled by two retinal specialists and included central fovea cross-section OCTs. Nine models were developed using the Visual Geometry Group 16 architecture to distinguish healthy versus abnormal retinas and to identify eight different retinal abnormality signs. A total of 21,500 OCT images were screened, and 10,770 central fovea cross-section OCTs were included in the study. The system achieved high accuracy in identifying healthy retinas and specific pathological signs, ranging from 93 to 99%. Accurately detecting abnormal retinal signs from OCT images is crucial for patient care. This study aimed to identify specific signs related to retinal pathologies, aiding ophthalmologists in diagnosis. The high-accuracy system identified healthy retinas and pathological signs, making it a useful diagnostic aid. Labelled OCT images remain a challenge, but our approach reduces dataset creation time and shows DL models’ potential to improve ocular pathology diagnosis and clinical decision-making.