bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian Paleomagnetic Euler Pole Inversion for Paleogeographic Reconstruction and Analysis
Authors: Rose Ian R. , Zhang Yiming , Swanson‐Hysell Nicholas L.
Published: September 2022

Apparent polar wander paths (APWPs) synthesized from paleomagnetic poles provide the most direct data for reconstructing past paleogeography and plate motions for times earlier than ca. 200 Ma. In this contribution, we describe a new method for APWP synthesis that extends the paleomagnetic Euler pole analysis of Gordon et al. (1984, https://doi.org/10.1029/TC003i005p00499) by placing it within the framework of a Bayesian inverse problem. This approach incorporates uncertainties in pole positions and age that are often ignored in standard treatments. The paleomagnetic Euler poles resulting from the inversions provide estimates for full‐vector plate motion (both latitude and longitude) and associated uncertainty. The method allows for inverting for one or more Euler poles with the timing of changepoints being solved as part of the inversion. In addition, the method allows the incorporation of true polar wander rotations, thus providing an avenue for probabilistic partitioning of plate tectonic motion and true polar wander based on paleomagnetic poles. We show example inversions on synthetic data to demonstrate the method's capabilities. We illustrate application of the method to Cenozoic Australia paleomagnetic poles which can be compared to independent plate reconstructions. A two‐Euler pole inversion for the Australian record recovers northward acceleration of Australia in the Eocene with rates that are consistent with plate reconstructions. We also apply the method to constrain rapid rates of motion for cratonic North America associated with the Keweenawan Track of late Mesoproterozoic paleomagnetic poles. The application of Markov chain Monte Carlo methods to estimate paleomagnetic Euler poles can open new directions in quantitative paleogeography.
Unchecked Ocean Warming Threatens Many Gulf and Caribbean Corals
Authors: Fritts Rachel
Published: September 2022

Gulf of Mexico and Caribbean sea surface temperatures could surpass coral bleaching thresholds in the region as soon as 2050, motivating the need for prompt mitigation, researchers say.
Magnetosphere‐Ionosphere‐Thermosphere Coupling Study at Jupiter Based on Juno's First 30 Orbits and Modeling Tools
Authors: Al Saati S. , Clément N. , Louis C. , Blanc M. , Wang Y. , André N. , Lamy L. , Bonfond B. , Collet B. , Allegrini F. , Bolton S. , Clark G. , Connerney J. E. P. , Gérard J.‐C. , Gladstone G. R. , Kotsiaros S. , Kurth W. S. , Mauk B.
Published: September 2022

The dynamics of the Jovian magnetosphere is controlled by the interplay of the planet's fast rotation, its solar‐wind interaction and its main plasma source at the Io torus, mediated by coupling processes involving its magnetosphere, ionosphere, and thermosphere. At the ionospheric level, these processes can be characterized by a set of parameters including conductances, field‐aligned currents, horizontal currents, electric fields, transport of charged particles along field lines including the fluxes of electrons precipitating into the upper atmosphere which trigger auroral emissions, and the particle and Joule heating power dissipation rates into the upper atmosphere. Determination of these key parameters makes it possible to estimate the net transfer of momentum and energy between Jovian upper atmosphere and equatorial magnetosphere. A method based on a combined use of Juno multi‐instrument data and three modeling tools was developed by Wang et al. (2021, https://doi.org/10.1029/2021ja029469) and applied to an analysis of the first nine orbits to retrieve these parameters along Juno's magnetic footprint. We extend this method to the first 30 Juno science orbits and to both hemispheres. Our results reveal a large variability of these parameters from orbit to orbit and between the two hemispheres. They also show dominant trends. Southern current systems are consistent with the generation of a region of sub‐corotating ionospheric plasma flows, while both super‐corotating and sub‐corotating plasma flows are found in the north. These results are discussed in light of the previous space and ground‐based observations and currently available models of plasma convection and current systems, and their implications are assessed.
Constraining the Carbon Budget of Peat Ecosystems: Application of Stoichiometry and Enthalpy Balances
Authors: Worrall Fred , Boothroyd Ian. M. , Clay Gareth D. , Moody Catherine S. , Heckman Katherine , Burt Tim P. , Rose Rob
Published: September 2022

We consider how the stoichiometry and energy content of organic matter reservoirs and fluxes through and from a peatland enable the fluxes and storage of carbon within a peatland to be constrained. We include the elemental composition of the above‐ and below‐ground biomass, litter, the peat profile, and the dissolved and particulate organic matter within a blanket bog in northern England for which the C budget has previously been measured. The study shows, based only on the elemental composition, and calculation of oxidation and energy contents, that: (a) Dissolved organic carbon (DOC) in first‐order streams is significantly more oxidized than in peat pore water but that there was no significant difference in organic carbon oxidation state down the peat profile; (b) The occurrence and speciation of N uptake and release in the peatland with N used and recycled can be predicted; (c) The relatively high oxidation state of DOC in stream water acts as an endpoint for peat‐forming reactions; (d) Methanogenesis does not result in deep peat formation as its requirement for energy consumes too much organic matter to form residual peat at depth; (e) Sulfate reduction does occur during the formation of deep peat; (f) Organic matter elemental composition could be constrained to within three bounding equations though the proportions of carbon species could not be specified. (g) The formation of deep peat in this catchment could only be achieved if the dissolved organic matter (DOM) in the peat pore water is the dominant electron acceptor and energy source in the production of residual organic matter; however, it is unclear as to the flux of DOM up or down the peat profile.
Delivering hypertension care in private-sector clinics of urban slum areas of India: the Mumbai Hypertension Project
Authors: Hegde Asha , Patel Haresh , Laxmeshwar Chinmay , Phalake Ajit , Khungar Pathni Anupam , Gandhi Ravdeep , Moran Andrew E. , Kannure Mandar , Sharma Bhawana , Jondhale Vaishnavi , Surendran Sapna , Vijayan Shibu
Published: September 2022

In India, the private sector provides 70% of the total outpatient medical care. This study describes the Mumbai Hypertension Project, which aimed to deliver a standard hypertension management package in private sector clinics situated in urban slums. The project was conducted in two wards (one “lean” and one “intensive”) with 82 private providers in each. All hypertensive patients received free drug vouchers, baseline serum creatinine, adherence support, self-management counseling and follow-up calls. In the intensive-ward, project supported hub agents facilitated uptake of services. A total of 13,184 hypertensive patients were registered from January 2019 to February 2020. Baseline blood pressure (BP) control rates were higher in the intensive-ward (30%) compared with the lean-ward (13%). During the 14-month project period, 6752 (51%) patients followed-up, with participants in the intensive-ward more likely to follow-up (aOR: 2.31; p < 0.001). By project end, the 3–6-month cohort control rate changed little from baseline—29% for intensive ward and 14% for lean ward. Among those who followed up, proportion with controlled BP increased 13 percentage points in the intensive ward and 16 percentage points in the lean ward; median time to BP control was 97 days in the intensive-ward and 153 days in lean-ward (p < 0.001). Despite multiple quality-improvement interventions in Mumbai private sector clinics, loss to follow-up remained high, and BP control rates only improved in patients who followed up; but did not improve overall. Only with new systems to organize and incentivize patient follow-up will the Indian private sector contribute to achieving national hypertension control goals.
Australian arm of the International Spinal Cord Injury (Aus-InSCI) community survey: 1. population-based design, methodology and cohort profile
Authors: Middleton James W. , Arora Mohit , Kifley Annette , Geraghty Timothy , Borg Samantha J. , Marshall Ruth , Clark Jillian , Nunn Andrew , Ferrante Anna , Fekete Christine , Stucki Gerold , Gopinath Bamini , Craig Ashley , Cameron Ian D.
Published: September 2022

Study design

Cross-sectional survey.

Objectives

To describe design and methods of Australian arm of International Spinal Cord Injury (Aus-InSCI) community survey, reporting on participation rates, potential non-response bias and cohort characteristics.

Setting

Survey of community-dwelling people with SCI at least 12 months post-injury, recruited between March 2018 and January 2019, from state-wide SCI services, a government insurance agency and not-for-profit consumer organisations across four Australian states.

Methods

The Aus-InSCI survey combined data for people with SCI from nine custodians, using secure data-linkage processes, to create a population-based, anonymised dataset. The Aus-InSCI questionnaire comprised 193 questions. Eligibility, response status and participation rates were calculated. Descriptive statistics depict participant characteristics. Logistic regression models were developed for probability of participation, and inverse probability weights generated to assess potential non-response bias.

Results

1579 adults with SCI were recruited, a cooperation rate of 29.4%. Participants were predominantly male (73%), with 50% married. Mean age was 57 years (range 19–94) and average time post-injury 17 years (range 1–73). Paraplegia (61%) and incomplete lesions (68%) were most common. Males were more likely than females to have traumatic injuries (p < 0.0001) and complete lesions (p = 0.0002), and younger age-groups were more likely to have traumatic injuries and tetraplegia (p < 0.0001). Potential non-response bias evaluated using selected outcomes was found to be negligible in the Aus-InSCI cohort.

Conclusions

The Aus-InSCI survey made efforts to maximise coverage, avoid recruitment bias and address non-response bias. The distributed, linked and coded (re-identifiable at each custodian level) ‘virtual quasi-registry’ data model supports systematic cross-sectional and longitudinal research.
For whom the bell tolls: psychopathological and neurobiological correlates of a DNA methylation index of time-to-death
Authors: Hawn Sage E. , Zhao Xiang , Sullivan Danielle R. , Logue Mark , Fein-Schaffer Dana , Milberg William , McGlinchey Regina , Miller Mark W. , Wolf Erika J.
Published: September 2022

Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge (“GrimAge residuals”), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness. Data from two independent trauma-exposed military cohorts (n = 647 [62.9% male, Mage = 52], n = 434 [90% male, Mage = 32]) were evaluated using linear regression models to test associations between GrimAge residuals, psychopathology, and health correlates. Externalizing psychopathology significantly predicted GrimAge residuals in both cohorts (ps < 0.028). PTSD predicted GrimAge residuals in the younger (p = 0.001) but not the older cohort. GrimAge residuals were associated with several neurobiological variables available in the younger cohort, including cognitive disinhibition (padj = 0.021), poorer memory recall (padj = 0.023), cardiometabolic pathology (padj < 0.001), oxidative stress (padj = 0.003), astrocyte damage (padj = 0.021), inflammation (C-reactive protein: padj < 0.001; IL-6: padj < 0.001), and immune functioning (padj < 0.001). A subset of inflammatory and neuropathology analytes were available in the older cohort and showed associations with GrimAge residuals (IL-6: padj < 0.001; TNF-α: padj < 0.001). GrimAge residuals were also associated with reduced cortical thickness in right lateral orbitofrontal cortex (padj = 0.018) and left fusiform gyrus (padj = 0.030), which are related to emotion regulation and facial recognition, respectively. Psychopathology may be a common risk factor for elevated mortality risk. GrimAge could help identify those at risk for adverse health outcomes and allow for early disease identification and treatment.
Comprehensive analysis of omics data identifies relevant gene networks for Attention-Deficit/Hyperactivity Disorder (ADHD)
Authors: Cabana-Domínguez Judit , Soler Artigas María , Arribas Lorena , Alemany Silvia , Vilar-Ribó Laura , Llonga Natalia , Fadeuilhe Christian , Corrales Montse , Richarte Vanesa , Ramos-Quiroga Josep Antoni , Ribasés Marta
Published: September 2022

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that results from the interaction of both genetic and environmental risk factors. Genome-wide association studies have started to identify multiple genetic risk loci associated with ADHD, however, the exact causal genes and biological mechanisms remain largely unknown. We performed a multi-step analysis to identify and characterize modules of co-expressed genes associated with ADHD using data from peripheral blood mononuclear cells of 270 ADHD cases and 279 controls. We identified seven ADHD-associated modules of co-expressed genes, some of them enriched in both genetic and epigenetic signatures for ADHD and in biological pathways relevant for psychiatric disorders, such as the regulation of gene expression, epigenetics and immune system. In addition, for some of the modules, we found evidence of potential regulatory mechanisms, including microRNAs and common genetic variants. In conclusion, our results point to promising genes and pathways for ADHD, supporting the use of peripheral blood to assess gene expression signatures in psychiatric disorders. Furthermore, they highlight that the combination of multi-omics signals provides deeper and broader insights into the biological mechanisms underlying ADHD.
Inflammatory gut as a pathologic and therapeutic target in Parkinson’s disease
Authors: Lee Jea-Young , Wang Zhen-Jie , Moscatello Alexa , Kingsbury Chase , Cozene Blaise , Farooq Jeffrey , Saft Madeline , Sadanandan Nadia , Gonzales-Portillo Bella , Zhang Henry , Salazar Felipe Esparza , Toledo Alma Rosa Lezama , Monroy Germán Rivera , Berlet Reed , Sanberg Cyndy D. , Sanberg Paul R. , Borlongan Cesario V.
Published: September 2022

Parkinson’s disease (PD) remains a significant unmet clinical need. Gut dysbiosis stands as a PD pathologic source and therapeutic target. Here, we assessed the role of the gut-brain axis in PD pathology and treatment. Adult transgenic (Tg) α-synuclein-overexpressing mice served as subjects and were randomly assigned to either transplantation of vehicle or human umbilical cord blood-derived stem cells and plasma. Behavioral and immunohistochemical assays evaluated the functional outcomes following transplantation. Tg mice displayed typical motor and gut motility deficits, elevated α-synuclein levels, and dopaminergic depletion, accompanied by gut dysbiosis characterized by upregulation of microbiota and cytokines associated with inflammation in the gut and the brain. In contrast, transplanted Tg mice displayed amelioration of motor deficits, improved sparing of nigral dopaminergic neurons, and downregulation of α-synuclein and inflammatory-relevant microbiota and cytokines in both gut and brain. Parallel in vitro studies revealed that cultured dopaminergic SH-SY5Y cells exposed to homogenates of Tg mouse-derived dysbiotic gut exhibited significantly reduced cell viability and elevated inflammatory signals compared to wild-type mouse-derived gut homogenates. Moreover, treatment with human umbilical cord blood-derived stem cells and plasma improved cell viability and decreased inflammation in dysbiotic gut-exposed SH-SY5Y cells. Intravenous transplantation of human umbilical cord blood-derived stem/progenitor cells and plasma reduced inflammatory microbiota and cytokine, and dampened α-synuclein overload in the gut and the brain of adult α-synuclein-overexpressing Tg mice. Our findings advance the gut-brain axis as a key pathological origin, as well as a robust therapeutic target for PD.
LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model
Authors: Zheng Quan-you , Li You , Liang Shen-ju , Chen Xi-ming , Tang Ming , Rao Zheng-sheng , Li Gui-qing , Feng Jian-Li , Zhong Yu , Chen Jian , Xu Gui-lian , Zhang Ke-qin
Published: September 2022

Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LTβR-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Moreover, LIGHT signaling augmented ischemic stress-induced mitochondrial dysfunction characterized by an imbalance in mitochondrial fission and fusion, decreased mtDNA copies, impaired mitophagy, and increased mitochondrial membrane potential (ΔΨm). Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LTβR signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI.
The genesis and evolution of acute myeloid leukemia stem cells in the microenvironment: From biology to therapeutic targeting
Authors: Chen Yongfeng , Li Jing , Xu Linglong , Găman Mihnea-Alexandru , Zou Zhenyou
Published: September 2022

Acute myeloid leukemia (AML) is a hematological malignancy characterized by cytogenetic and genomic alterations. Up to now, combination chemotherapy remains the standard treatment for leukemia. However, many individuals diagnosed with AML develop chemotherapeutic resistance and relapse. Recently, it has been pointed out that leukemic stem cells (LSCs) are the fundamental cause of drug resistance and AML relapse. LSCs only account for a small subpopulation of all leukemic cells, but possess stem cell properties, including a self-renewal capacity and a multi-directional differentiation potential. LSCs reside in a mostly quiescent state and are insensitive to chemotherapeutic agents. When LSCs reside in a bone marrow microenvironment (BMM) favorable to their survival, they engage into a steady, continuous clonal evolution to better adapt to the action of chemotherapy. Most chemotherapeutic drugs can only eliminate LSC-derived clones, reducing the number of leukemic cells in the BM to a normal range in order to achieve complete remission (CR). LSCs hidden in the BM niche can hardly be targeted or eradicated, leading to drug resistance and AML relapse. Understanding the relationship between LSCs, the BMM, and the generation and evolution laws of LSCs can facilitate the development of effective therapeutic targets and increase the efficiency of LSCs elimination in AML.
The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems
Authors: Lasker Keren , Boeynaems Steven , Lam Vinson , Scholl Daniel , Stainton Emma , Briner Adam , Jacquemyn Maarten , Daelemans Dirk , Deniz Ashok , Villa Elizabeth , Holehouse Alex S. , Gitler Aaron D. , Shapiro Lucy
Published: September 2022

Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells.
Rapid vertical exchange at fronts in the Northern Gulf of Mexico
Authors: Qu Lixin , Thomas Leif N. , Wienkers Aaron F. , Hetland Robert D. , Kobashi Daijiro , Taylor John R. , Hsu Fucent Hsuan Wei , MacKinnon Jennifer A. , Shearman R. Kipp , Nash Jonathan D.
Published: September 2022

Over the Texas-Louisiana Shelf in the Northern Gulf of Mexico, the eutrophic, fresh Mississippi/Atchafalaya river plume isolates saltier waters below, supporting the formation of bottom hypoxia in summer. The plume also generates strong density fronts, features of the circulation that are known pathways for the exchange of water between the ocean surface and the deep. Using high-resolution ocean observations and numerical simulations, we demonstrate how the summer land-sea breeze generates rapid vertical exchange at the plume fronts. We show that the interaction between the land-sea breeze and the fronts leads to convergence/divergence in the surface mixed layer, which further facilitates a slantwise circulation that subducts surface water along isopycnals into the interior and upwells bottom waters to the surface. This process causes significant vertical displacements of water parcels and creates a ventilation pathway for the bottom water in the northern Gulf. The ventilation of bottom water can bypass the stratification barrier associated with the Mississippi/Atchafalaya river plume and might impact the dynamics of the region’s dead zone.
A Dilp8-dependent time window ensures tissue size adjustment in Drosophila
Authors: Blanco-Obregon D. , El Marzkioui K. , Brutscher F. , Kapoor V. , Valzania L. , Andersen D. S. , Colombani J. , Narasimha S. , McCusker D. , Léopold P. , Boulan L.
Published: September 2022

The control of organ size mainly relies on precise autonomous growth programs. However, organ development is subject to random variations, called developmental noise, best revealed by the fluctuating asymmetry observed between bilateral organs. The developmental mechanisms ensuring bilateral symmetry in organ size are mostly unknown. In Drosophila, null mutations for the relaxin-like hormone Dilp8 increase wing fluctuating asymmetry, suggesting that Dilp8 plays a role in buffering developmental noise. Here we show that size adjustment of the wing primordia involves a peak of dilp8 expression that takes place sharply at the end of juvenile growth. Wing size adjustment relies on a cross-organ communication involving the epidermis as the source of Dilp8. We identify ecdysone signaling as both the trigger for epidermal dilp8 expression and its downstream target in the wing primordia, thereby establishing reciprocal hormonal feedback as a systemic mechanism, which controls organ size and bilateral symmetry in a narrow developmental time window.
Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates
Authors: Zhang Yao , Qiao Deyong , Duan Mei , Wang You , Zhu Shaolin
Published: September 2022

Chiral α-aminoboronic acids and their derivatives are generally useful as bioactive compounds and some have been approved as therapeutic agents. Here we report a NiH-catalysed asymmetric hydroamidation process that with a simple amino alcohol ligand can easily produce a wide range of highly enantioenriched α-aminoboronates from alkenyl boronates and dioxazolones under mild conditions. The reaction is proposed to proceed by an enantioselective hydrometallation followed by an inner-sphere nitrenoid transfer and C–N bond forming sequence. The synthetic utility of this transformation was demonstrated by the efficient synthesis of a current pharmaceutical agent, Vaborbactam.
Experimental unsupervised learning of non-Hermitian knotted phases with solid-state spins
Authors: Yu Yefei , Yu Li-Wei , Zhang Wengang , Zhang Huili , Ouyang Xiaolong , Liu Yanqing , Deng Dong-Ling , Duan L.-M.
Published: September 2022

Non-Hermiticity has widespread applications in quantum physics. It brings about distinct topological phases without Hermitian counterparts, and gives rise to the fundamental challenge of phase classification. Here, we report an experimental demonstration of unsupervised learning of non-Hermitian topological phases with the nitrogen-vacancy center platform. In particular, we implement the non-Hermitian twister model, which hosts peculiar knotted topological phases, with a solid-state quantum simulator consisting of an electron spin and a nearby 13C nuclear spin in a nitrogen-vacancy center in diamond. By tuning the microwave pulses, we efficiently generate a set of experimental data without phase labels. Furthermore, based on the diffusion map method, we cluster this set of experimental raw data into three different knotted phases in an unsupervised fashion without a priori knowledge of the system, which is in sharp contrast to the previously implemented supervised learning phases of matter. Our results showcase the intriguing potential for autonomous classification of exotic unknown topological phases with experimental raw data.
Safety and immune response kinetics of GRAd-COV2 vaccine: phase 1 clinical trial results
Authors: Agrati Chiara , Castilletti Concetta , Battella Simone , Cimini Eleonora , Matusali Giulia , Sommella Andrea , Sacchi Alessandra , Colavita Francesca , Contino Alessandra M. , Bordoni Veronica , Meschi Silvia , Gramigna Giulia , Barra Federica , Grassi Germana , Bordi Licia , Lapa Daniele , Notari Stefania , Casetti Rita , Bettini Aurora , Francalancia Massimo , Ciufoli Federica , Vergori Alessandra , Vita Serena , Gentile Michela , Raggioli Angelo , Plazzi Maria M. , Bacchieri Antonella , Nicastri Emanuele , Antinori Andrea , Milleri Stefano , Lanini Simone , Colloca Stefano , Girardi Enrico , Camerini Roberto , Ippolito Giuseppe , Vaia Francesco , Folgori Antonella , Capone Stefania
Published: September 2022

Despite the successful deployment of efficacious vaccines and therapeutics, the development of novel vaccines for SARS-CoV-2 remains a major goal to increase vaccine doses availability and accessibility for lower income setting. We report here on the kinetics of Spike-specific humoral and T-cell response in young and old volunteers over 6 months follow-up after a single intramuscular administration of GRAd-COV2, a gorilla adenoviral vector-based vaccine candidate currently in phase-2 of clinical development. At all three tested vaccine dosages, Spike binding and neutralizing antibodies were induced and substantially maintained up to 3 months, to then contract at 6 months. Potent T-cell responses were readily induced and sustained throughout the study period, with only minor decline. No major differences in immune response to GRAd-COV2 vaccination were observed in the two age cohorts. In light of its favorable safety and immunogenicity, GRAd-COV2 is a valuable candidate for further clinical development and potential addition to the COVID-19 vaccine toolbox to help fighting SARS-CoV-2 pandemic.
Design and test of smashing and scattering device of double-channel feeding ratoon rice harvester
Authors: Fu Jianwei , Ji Chao , Wang Weikang , Liu Haopeng , Zhang Guozhong , Gao Yuan , Zhou Yong , Abdeen Mohamed Anwer
Published: September 2022

Since it is requested that the smashed straw should not be scattered onto the stubble in the first season harvest, a smashing and scattering device matched with the first season harvester of ratoon rice was designed in this paper to smash and scatter the straw into the rolling area. The main structural parameters affecting the straw scattering performance were determined by theoretical analysis of the deflecting performance of the straw deflector. EDEM software was used to simulate and analyze the straw scattering situation under the action of the deflector. Taking the qualified rate of straw scattering as the performance index, the optimal parameter combination of the straw deflector was determined by L27 (313) orthogonal test, and the operating performance of the device was verified by bench test and field comparison test. The test results show that: The optimal parameter combination was 45° between the straw deflector and the vertical direction, 200 mm height difference between straw deflector and outlet, 0° inclination angle of inner deflector and 35° inclination angle of outer deflector. The qualified rate of straw scattering was 72.2% in the corresponding simulation test, 93.6% in the bench test and 95.2% in the field test, which could meet the demand of first season harvest of ratoon rice.
Optimal selective floor cleaning using deep learning algorithms and reconfigurable robot hTetro
Authors: Ramalingam Balakrishnan , Le Anh Vu , Lin Zhiping , Weng Zhenyu , Mohan Rajesh Elara , Pookkuttath Sathian
Published: September 2022

Floor cleaning robots are widely used in public places like food courts, hospitals, and malls to perform frequent cleaning tasks. However, frequent cleaning tasks adversely impact the robot’s performance and utilize more cleaning accessories (such as brush, scrubber, and mopping pad). This work proposes a novel selective area cleaning/spot cleaning framework for indoor floor cleaning robots using RGB-D vision sensor-based Closed Circuit Television (CCTV) network, deep learning algorithms, and an optimal complete waypoints path planning method. In this scheme, the robot will clean only dirty areas instead of the whole region. The selective area cleaning/spot cleaning region is identified based on the combination of two strategies: tracing the human traffic patterns and detecting stains and trash on the floor. Here, a deep Simple Online and Real-time Tracking (SORT) human tracking algorithm was used to trace the high human traffic region and Single Shot Detector (SSD) MobileNet object detection framework for detecting the dirty region. Further, optimal shortest waypoint coverage path planning using evolutionary-based optimization was incorporated to traverse the robot efficiently to the designated selective area cleaning/spot cleaning regions. The experimental results show that the SSD MobileNet algorithm scored 90% accuracy for stain and trash detection on the floor. Further, compared to conventional methods, the evolutionary-based optimization path planning scheme reduces 15% percent of navigation time and 10% percent of energy consumption.
Correlation between COVID-19 severity and previous exposure of patients to Borrelia spp.
Authors: Szewczyk-Dąbrowska Alina , Budziar Wiktoria , Harhala Marek , Baniecki Krzysztof , Pikies Aleksandra , Jędruchniewicz Natalia , Kaźmierczak Zuzanna , Gembara Katarzyna , Klimek Tomasz , Witkiewicz Wojciech , Nahorecki Artur , Barczyk Kamil , Kłak Marlena , Grata-Borkowska Urszula , Dąbrowska Krystyna
Published: September 2022

Predictors for the risk of severe COVID-19 are crucial for patient care and control of the disease. Other infectious diseases as potential comorbidities in SARS-CoV-2 infection are still poorly understood. Here we identify association between the course of COVID-19 and Lyme disease (borreliosis), caused by Borrelia burgdorferi transmitted to humans by ticks. Exposure to Borrelia was identified by multi-antigenic (19 antigens) serological testing of patients: severe COVID-19 (hospitalized), asymptomatic to mild COVID-19 (home treated or not aware of being infected), and not infected with SARS-CoV-2. Increased levels of Borrelia-specific IgGs strongly correlated with COVID-19 severity and risk of hospitalization. This suggests that a history of tick bites and related infections may contribute to the risks in COVID-19. Though mechanisms of this link is not clear yet, screening for antibodies targeting Borrelia may help accurately assess the odds of hospitalization for SARS-CoV-2 infected patients, supporting efforts for efficient control of COVID-19.
Mannan-binding lectin serine protease-2 (MASP-2) in human kidney and its relevance for proteolytic activation of the epithelial sodium channel
Authors: Zachar Rikke , Thiel Steffen , Hansen Søren , Henriksen Maiken Lumby , Skjoedt Mikkel-Ole , Skjodt Karsten , Hamzaei Zohra , Madsen Kirsten , Lund Lars , Hummler Edith , Svenningsen Per , Jensen Boye Lagerbon
Published: September 2022

Proteolytic activation of the renal epithelial sodium channel (ENaC) is increased by aldosterone. The aldosterone-sensitive protease remains unidentified. In humans, elevated circulating aldosterone is associated with increased urinary extracellular vesicle (uEVs) excretion of mannan-binding lectin associated serine protease-2 (MASP-2). We hypothesized that MASP-2 is a physiologically relevant ENaC-activating protease. It was confirmed that MASP2 mRNA is abundantly present in liver but not in human and mouse kidneys. Aldosterone-stimulation of murine cortical colleting duct (mCCD) cells did not induce MASP-2 mRNA. In human kidney collecting duct, MASP-2 protein was detected in AQP2-negative/ATP6VB1-positive intercalated cells suggestive of MASP2 protein uptake. Plasma concentration of full-length MASP-2 and the short splice variant MAp19 were not changed in a cross-over intervention study in healthy humans with low (70 mmol/day) versus high (250 mmol/day) Na+intake despite changes in aldosterone. The ratio of MAp19/MASP-2 in plasma was significantly increased with a high Na+diet and the ratio correlated with changes in aldosterone and fractional Na+excretion. MASP-2 was not detected in crude urine or in uEVs. MASP2 activated an amiloride-sensitive current when co-expressed with ENaC inXenopusoocytes, but not when added to the bath solution. In monolayers of collecting duct M1 cells, MASP2 expression did not increase amiloride-sensitive current and in HEK293 cells, MASP-2 did not affect γENaC cleavage. MASP-2 is neither expressed nor co-localized and co-regulated with ENaC in the human kidney or in urine after low Na+intake. MASP-2 does not mediate physiological ENaC cleavage in low salt/high aldosterone settings.
Selective modulation of cortical population dynamics during neuroprosthetic skill learning
Authors: Zippi Ellen L. , You Albert K. , Ganguly Karunesh , Carmena Jose M.
Published: September 2022

Brain-machine interfaces (BMIs) provide a framework for studying how cortical population dynamics evolve over learning in a task in which the mapping between neural activity and behavior is precisely defined. Learning to control a BMI is associated with the emergence of coordinated neural dynamics in populations of neurons whose activity serves as direct input to the BMI decoder (direct subpopulation). While previous work shows differential modification of firing rate modulation in this population relative to a population whose activity was not directly input to the BMI decoder (indirect subpopulation), little is known about how learning-related changes in cortical population dynamics within these groups compare.To investigate this, we monitored both direct and indirect subpopulations as two macaque monkeys learned to control a BMI. We found that while the combined population increased coordinated neural dynamics, this increase in coordination was primarily driven by changes in the direct subpopulation. These findings suggest that motor cortex refines cortical dynamics by increasing neural variance throughout the entire population during learning, with a more pronounced coordination of firing activity in subpopulations that are causally linked to behavior.
Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes
Authors: Wen Qingfeng , Verheijen Marcha , Wittens Mandy Melissa Jane , Czuryło Julia , Engelborghs Sebastiaan , Hauser Duncan , van Herwijnen Marcel H. M. , Lundh Thomas , Bergdahl Ingvar A. , Kyrtopoulos Soterios A. , de Kok Theo M. , Smeets Hubert J. M. , Briedé Jacco Jan , Krauskopf Julian
Published: September 2022

Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs’ gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.
Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer
Authors: Al-Qasem Abeer J. , Alves Carla L. , Ehmsen Sidse , Tuttolomondo Martina , Terp Mikkel G. , Johansen Lene E. , Vever Henriette , Hoeg Luna V. A. , Elias Daniel , Bak Martin , Ditzel Henrik J.
Published: September 2022

Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.
The Musashi proteins direct post-transcriptional control of protein expression and alternate exon splicing in vertebrate photoreceptors
Authors: Matalkah Fatimah , Jeong Bohye , Sheridan Macie , Horstick Eric , Ramamurthy Visvanathan , Stoilov Peter
Published: September 2022

The Musashi proteins, MSI1 and MSI2, are conserved RNA binding proteins with a role in the maintenance and renewal of stem cells. Contrasting with this role, terminally differentiated photoreceptor cells express high levels of MSI1 and MSI2, pointing to a role for the two proteins in vision. Combined knockout of Msi1 and Msi2 in mature photoreceptor cells abrogated the retinal response to light and caused photoreceptor cell death. In photoreceptor cells the Musashi proteins perform distinct nuclear and cytoplasmic functions. In the nucleus, the Musashi proteins promote splicing of photoreceptor-specific alternative exons. Surprisingly, conserved photoreceptor-specific alternative exons in genes critical for vision proved to be dispensable, raising questions about the selective pressures that lead to their conservation. In the cytoplasm MSI1 and MSI2 activate protein expression. Loss of Msi1 and Msi2 lead to reduction in the levels of multiple proteins including proteins required for vision and photoreceptor survival. The requirement for MSI1 and MSI2 in terminally differentiated photoreceptors alongside their role in stem cells shows that, depending on cellular context, these two proteins can control processes ranging from cell proliferation to sensory perception.
Improving the stability of inverted perovskite solar cells towards commercialization
Authors: Li Bowei , Zhang Wei
Published: September 2022

Inverted perovskite solar cells (IPSCs) have great potential for commercialization, in terms of compatibility with flexible and multijunction solar cells. However, non-ideal stability limits their entry into the market. To shed light on the unstable origins of IPSCs, an analysis of recent research progress is needed. Here, we systematically discuss the stability of IPSCs, including each functional layer, interface and entire device, and consider environmental and operational stressors. We summarize a range of strategies for improving device stability and discuss the significance of stability test protocols. Finally, we highlight the shortcomings of current approaches for stability improvement and assessment, and provide recommendations for improving the stability of IPSCs.
Development of novel enzyme immobilization methods employing formaldehyde or triethoxysilylbutyraldehyde to fabricate immobilized enzyme microreactors for peptide mapping
Authors: Ku Kenneth , Frey Connor , Arad Maor , Ghafourifar Golfam
Published: September 2022

The digestion of proteins with proteolytic enzymes has expedited the analysis of peptide mapping.
Simultaneous and sensitive determination of the main metabolites of the plasticizer DEHP and its substitutes DEHTP, DINCH and TEHTM in human urine by coupling of on-line SPE, UHPLC and tandem mass spectrometry
Authors: Kuhlmann Laura , Münch Frank , Göen Thomas , Eckert Elisabeth
Published: September 2022

On-line SPE-LC-MS/MS method for the simultaneous determination of the most relevant urinary biomarkers of exposure to DEHP and the alternative plasticizers DINCH, DEHTP and TEHTM.
Sensitive bioanalytical methods for telomerase activity detection: a cancer biomarker
Authors: Afshari Nasim , Al-Gazally Moaed E. , Rasulova Iroda , Jalil Abduladheem Turki , Matinfar Solmaz , Momeninejad Mohsen
Published: September 2022

Telomerase is an enzyme that protects the length of telomeres by adding guanine-rich repetitive sequences. In tumors, gametes, and stem cells, telomerase activity is exerted.
Site-specific unnatural base excision via visible light
Authors: Guo Yuan-Yang , Zhang Rujie , Huo Bianbian , Wang Luying , Yuan Donghe , Bai Jingsi , Wang Honglei , Zhu Gongming , Zhang Xiguang , Zhu Anlian , Chen Tingjian , Li Lingjun
Published: September 2022

In this paper, we report a visible-light-induced method to construct site-specific unnatural base excision (BE) and show the influence of its regulation on transcription and translation levels.
A homoleptic tris(diphosphacyclobutadiene) tripledecker sandwich complex
Authors: Rödl Christian , Hierlmeier Gabriele , Wolf Robert
Published: September 2022

The first tripledecker sandwich complex exclusively containing (diphospha)cyclobutadiene ligands was synthesised via an unexpected route and structurally characterised. An analysis of the bonding situation and redox behaviour is presented.
Fe2O3 supported Pt single atom catalysts for the selective hydrogenation of cinnamaldehyde
Authors: Lan Huanshi , Qin Zuzeng , Shi Shaolin , Zhang Xingcong , He Xiaohui , Ji Hongbing
Published: September 2022

A simple ball milling method was adopted to prepare single atom catalysts with excellent catalytic properties.
Analysing the role of anions in the synthesis of catalytically active urea-based MOFs
Authors: Ghosh Dipankar , Damodaran Krishna K.
Published: September 2022

Urea-based MOF synthesised in the presence of sulphate anion yielded a versatile catalyst, but MOFs derived from other anions were catalytically inactive, indicating that sulphate anion act as a reaction template to generate catalytically active MOFs.
A modified xanthine oxidase cell model for screening of antihyperuricemic functional compounds
Authors: Hou Chuanli , Sha Wangqian , Li Yujuan , Yao Maojin , Ren Jiaoyan
Published: September 2022

A cell model for hyperuricemia was established, in vitro, employing cultured HK-2 cells. It was validated for rapid screening of urate-lowering compounds. It may be used as an in vitro model to screen antihyperuricemic compounds that mimic in vivo cell growth patterns.
Widespread vertical transmission of secretory immunoglobulin A coated trace bacterial variants from the mother to infant gut through breastfeeding
Authors: Qi Ce , Tu Huayu , Zhou Jingbo , Tu Rundan , Chang Hong , Chen Jie , Hu Haiting , Yu Renqiang , Sun Jin
Published: September 2022

Gut microbiota transmission from mother to offspring is critical to infant gut microbiota and immune development.
Preparation of curcumin-loaded cochleates: characterisation, stability and antioxidant properties
Authors: Chen Lijuan , Yue Bowen , Liu Zhiming , Luo Yali , Ni Lu , Shen Wen , Zhou Zhiyong , Ge Xuemei
Published: September 2022

CUR-Cochleates were prepared to improve the stability and uptake efficiency of CUR. The antioxidant effects indicating that CUR-Cochs effectively reduce the NIH3T3 cell damage caused by H2O2, which could provide the feasibility to be developed in functional foods.
Salvia hispanicaL. (chia) seed improves liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome
Authors: Vega Joubert Michelle Berenice , Degrave Valentina , Ingaramo Paola , Oliva María Eugenia , D'Alessandro María Eugenia
Published: September 2022

The aim of study were to analyze liver inflammation and endothelial dysfunction in an experimental model of Metabolic Syndrome induced by administration of a sucrose-rich diet and to evaluate the effects of chia seed as a therapeutic strategy.