bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptains block retinal ganglion cell death in animal models of ocular hypertension: implications for neuroprotection in glaucoma
Authors: Nam Mi-Hyun , Stankowska Dorota L. , Johnson Gretchen A. , Nahomi Rooban B. , Pantcheva Mina B. , Nagaraj Ram H. 
Published: November 2022

AbstractOcular hypertension is a significant risk factor for vision loss in glaucoma due to the death of retinal ganglion cells (RGCs). This study investigated the effects of the antiapoptotic peptides peptain-1 and peptain-3a on RGC death in vitro in rat primary RGCs and in mouse models of ocular hypertension. Apoptosis was induced in primary rat RGCs by trophic factor deprivation for 48 h in the presence or absence of peptains. The effects of intravitreally injected peptains on RGC death were investigated in mice subjected to retinal ischemic/reperfusion (I/R) injury and elevated intraocular pressure (IOP). I/R injury was induced in mice by elevating the IOP to 120 mm Hg for 1 h, followed by rapid reperfusion. Ocular hypertension was induced in mice by injecting microbeads (MB) or silicone oil (SO) into the anterior chamber of the eye. Retinal flatmounts were immunostained with RGC and activated glial markers. Effects on anterograde axonal transport were determined by intravitreal injection of cholera toxin-B. Peptain-1 and peptain-3a inhibited neurotrophic factor deprivation-mediated RGC apoptosis by 29% and 35%, respectively. I/R injury caused 52% RGC loss, but peptain-1 and peptain-3a restricted RGC loss to 13% and 16%, respectively. MB and SO injections resulted in 31% and 36% loss in RGCs following 6 weeks and 4 weeks of IOP elevation, respectively. Peptain-1 and peptain-3a inhibited RGC death; the loss was only 4% and 12% in MB-injected eyes and 16% and 15% in SO-injected eyes, respectively. Anterograde transport was defective in eyes with ocular hypertension, but this defect was substantially ameliorated in peptain-injected eyes. Peptains suppressed ocular hypertension-mediated retinal glial activation. In summary, our results showed that peptains block RGC somal and axonal damage and neuroinflammation in animal models of glaucoma. We propose that peptains have the potential to be developed as therapeutics against neurodegeneration in glaucoma.
Quantum metrology with imperfect measurements
Authors: Len Yink Loong , Gefen Tuvia , Retzker Alex , Kołodyński Jan 
Published: November 2022

AbstractThe impact of measurement imperfections on quantum metrology protocols has not been approached in a systematic manner so far. In this work, we tackle this issue by generalising firstly the notion of quantum Fisher information to account for noisy detection, and propose tractable methods allowing for its approximate evaluation. We then show that in canonical scenarios involving N probes with local measurements undergoing readout noise, the optimal sensitivity depends crucially on the control operations allowed to counterbalance the measurement imperfections—with global control operations, the ideal sensitivity (e.g., the Heisenberg scaling) can always be recovered in the asymptotic N limit, while with local control operations the quantum-enhancement of sensitivity is constrained to a constant factor. We illustrate our findings with an example of NV-centre magnetometry, as well as schemes involving spin-1/2 probes with bit-flip errors affecting their two-outcome measurements, for which we find the input states and control unitary operations sufficient to attain the ultimate asymptotic precision.
Interruption of post-Golgi STING trafficking activates tonic interferon signaling
Authors: Tu Xintao , Chu Ting-Ting , Jeltema Devon , Abbott Kennady , Yang Kun , Xing Cong , Han Jie , Dobbs Nicole , Yan Nan 
Published: November 2022

AbstractActivation of the cGAS-STING pathway is traditionally considered a “trigger-release” mechanism where detection of microbial DNA or cyclic di-nucleotides sets off the type I interferon response. Whether this pathway can be activated without pathogenic ligand exposure is less well understood. Here we show that loss of Golgi-to-lysosome STING cofactors, but not ER-to-Golgi cofactors, selectively activates tonic interferon signalling. Impairment of post-Golgi trafficking extends STING Golgi-dwell time, resulting in elevated immune signalling and protection against infection. Mechanistically, trans-Golgi coiled coil protein GCC2 and several RAB GTPases act as key regulators of STING post-Golgi trafficking. Genomic deletion of these factors potently activates cGAS-STING signalling without instigating any pathogenic trigger for cGAS. Gcc2−/− mice develop STING-dependent serologic autoimmunity. Gcc2-deleted or Rab14-deleted cancer cells induce T-cell and IFN-dependent anti-tumour immunity and inhibit tumour growth in mice. In summary, we present a “basal flux” mechanism for tonic cGAS-STING signalling, regulated at the level of post-Golgi STING trafficking, which could be exploited for cancer immunotherapy.
Two simple movement mechanisms for spatial division of labour in social insects
Authors: Richardson Thomas O. , Stroeymeyt Nathalie , Crespi Alessandro , Keller Laurent 
Published: November 2022

AbstractMany animal species divide space into a patchwork of home ranges, yet there is little consensus on the mechanisms individuals use to maintain fidelity to particular locations. Theory suggests that animal movement could be based upon simple behavioural rules that use local information such as olfactory deposits, or global strategies, such as long-range biases toward landmarks. However, empirical studies have rarely attempted to distinguish between these mechanisms. Here, we perform individual tracking experiments on four species of social insects, and find that colonies consist of different groups of workers that inhabit separate but partially-overlapping spatial zones. Our trajectory analysis and simulations suggest that worker movement is consistent with two local mechanisms: one in which workers increase movement diffusivity outside their primary zone, and another in which workers modulate turning behaviour when approaching zone boundaries. Parallels with other organisms suggest that local mechanisms might represent a universal method for spatial partitioning in animal populations.
Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis
Authors: Huang Jian , Zhao Lei , Malik Shikha , Gentile Benjamin R. , Xiong Va , Arazi Tzahi , Owen Heather A. , Friml Jiří , Zhao Dazhong 
Published: November 2022

AbstractGermline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.
Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid
Authors: Branco Mariana A. , Dias Tiago P. , Cabral Joaquim M. S. , Pinto-do-Ó Perpetua , Diogo Maria Margarida 
Published: November 2022

AbstractThe epicardium, the outer epithelial layer that covers the myocardium, derives from a transient organ known as pro-epicardium, crucial during heart organogenesis. The pro-epicardium develops from lateral plate mesoderm progenitors, next to septum transversum mesenchyme, a structure deeply involved in liver embryogenesis. Here we describe a self-organized human multilineage organoid that recreates the co-emergence of pro-epicardium, septum transversum mesenchyme and liver bud. Additionally, we study the impact of WNT, BMP and retinoic acid signaling modulation on multilineage organoid specification. By co-culturing these organoids with cardiomyocyte aggregates, we generated a self-organized heart organoid comprising an epicardium-like layer that fully surrounds a myocardium-like tissue. These heart organoids recapitulate the impact of epicardial cells on promoting cardiomyocyte proliferation and structural and functional maturation. Therefore, the human heart organoids described herein, open the path to advancing knowledge on how myocardium-epicardium interaction progresses during heart organogenesis in healthy or diseased settings.
Understanding soil selenium accumulation and bioavailability through size resolved and elemental characterization of soil extracts
Authors: Tolu Julie , Bouchet Sylvain , Helfenstein Julian , Hausheer Olivia , Chékifi Sarah , Frossard Emmanuel , Tamburini Federica , Chadwick Oliver A. , Winkel Lenny H. E. 
Published: November 2022

AbstractDietary deficiency of selenium is a global health threat related to low selenium concentrations in crops. Despite the chemical similarity of selenium to the two more abundantly studied elements sulfur and arsenic, the understanding of its accumulation in soils and availability for plants is limited. The lack of understanding of soil selenium cycling is largely due to the unavailability of methods to characterize selenium species in soils, especially the organic ones. Here we develop a size-resolved multi-elemental method using liquid chromatography and elemental mass spectrometry, which enables an advanced characterization of selenium, sulfur, and arsenic species in soil extracts. We apply the analytical approach to soils sampled along the Kohala rainfall gradient on Big Island (Hawaii), which cover a large range of organic carbon and (oxy)hydroxides contents. Similarly to sulfur but contrarily to arsenic, a large fraction of selenium is found associated with organic matter in these soils. However, while sulfur and arsenic are predominantly found as oxyanions in water extracts, selenium mainly exists as small hydrophilic organic compounds. Combining Kohala soil speciation data with concentrations in parent rock and plants further suggests that selenium association with organic matter limits its mobility in soils and availability for plants.
Full-spectrum nonmetallic plasmonic carriers for efficient isopropanol dehydration
Authors: Lu Changhai , You Daotong , Li Juan , Wen Long , Li Baojun , Guo Tuan , Lou Zaizhu 
Published: November 2022

AbstractPlasmonic hot carriers have the advantage of focusing, amplifying, and manipulating optical signals via electron oscillations which offers a feasible pathway to influence catalytic reactions. However, the contribution of nonmetallic hot carriers and thermal effects on the overall reactions are still unclear, and developing methods to enhance the efficiency of the catalysis is critical. Herein, we proposed a new strategy for flexibly modulating the hot electrons using a nonmetallic plasmonic heterostructure (named W18O49-nanowires/reduced-graphene-oxides) for isopropanol dehydration where the reaction rate was 180-fold greater than the corresponding thermocatalytic pathway. The key detail to this strategy lies in the synergetic utilization of ultraviolet light and visible-near-infrared light to enhance the hot electron generation and promote electron transfer for C-O bond cleavage during isopropanol dehydration reaction. This, in turn, results in a reduced reaction activation barrier down to 0.37 eV (compared to 1.0 eV of thermocatalysis) and a significantly improved conversion efficiency of 100% propylene from isopropanol. This work provides an additional strategy to modulate hot carrier of plasmonic semiconductors and helps guide the design of better catalytic materials and chemistries.
Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics
Authors: Raducanu Vlad-Stefan , Tehseen Muhammad , Al-Amodi Amani , Joudeh Luay I. , De Biasio Alfredo , Hamdan Samir M. 
Published: November 2022

AbstractThe final steps of lagging strand synthesis induce maturation of Okazaki fragments via removal of the RNA primers and ligation. Iterative cycles between Polymerase δ (Polδ) and Flap endonuclease-1 (FEN1) remove the primer, with an intermediary nick structure generated for each cycle. Here, we show that human Polδ is inefficient in releasing the nick product from FEN1, resulting in non-processive and remarkably slow RNA removal. Ligase 1 (Lig1) can release the nick from FEN1 and actively drive the reaction toward ligation. These mechanisms are coordinated by PCNA, which encircles DNA, and dynamically recruits Polδ, FEN1, and Lig1 to compete for their substrates. Our findings call for investigating additional pathways that may accelerate RNA removal in human cells, such as RNA pre-removal by RNase Hs, which, as demonstrated herein, enhances the maturation rate ~10-fold. They also suggest that FEN1 may attenuate the various activities of Polδ during DNA repair and recombination.
Design of large-span stick-slip freely switchable hydrogels via dynamic multiscale contact synergy
Authors: Zhang Zhizhi , Qin Chenxi , Feng Haiyan , Xiang Yangyang , Yu Bo , Pei Xiaowei , Ma Yanfei , Zhou Feng 
Published: November 2022

AbstractSolid matter that can rapidly and reversibly switch between adhesive and non-adhesive states is desired in many technological domains including climbing robotics, actuators, wound dressings, and bioelectronics due to the ability for on-demand attachment and detachment. For most types of smart adhesive materials, however, reversible switching occurs only at narrow scales (nanoscale or microscale), which limits the realization of interchangeable surfaces with distinct adhesive states. Here, we report the design of a switchable adhesive hydrogel via dynamic multiscale contact synergy, termed as DMCS-hydrogel. The hydrogel rapidly switches between slippery (friction ~0.04 N/cm2) and sticky (adhesion ~3 N/cm2) states in the solid-solid contact process, exhibits large span, is switchable and dynamic, and features rapid adhesive switching. The design strategy of this material has wide applications ranging from programmable adhesive materials to intelligent devices.
A correlation-based feature analysis of physical examination indicators can help predict the overall underlying health status using machine learning
Authors: Wang Haixin , Shuai Ping , Deng Yanhui , Yang Jiyun , Shi Yi , Li Dongyu , Yong Tao , Liu Yuping , Huang Lulin 
Published: November 2022

AbstractAs a systematic investigation of the correlations between physical examination indicators (PEIs) is lacking, most PEIs are currently independently used for disease warning. This results in the general physical examination having limited diagnostic values. Here, we systematically analyzed the correlations in 221 PEIs between healthy and 34 unhealthy statuses in 803,614 individuals in China. Specifically, the study population included 711,928 healthy participants, 51,341 patients with hypertension, 12,878 patients with diabetes, and 34,997 patients with other unhealthy statuses. We found rich relevance between PEIs in the healthy physical status (7662 significant correlations, 31.5%). However, in the disease conditions, the PEI correlations changed. We focused on the difference in PEIs between healthy and 35 unhealthy physical statuses and found 1239 significant PEI differences, suggesting that they could be candidate disease markers. Finally, we established machine learning algorithms to predict health status using 15–16% of the PEIs through feature extraction, reaching a 66–99% accurate prediction, depending on the physical status. This new reference of the PEI correlation provides rich information for chronic disease diagnosis. The developed machine learning algorithms can fundamentally affect the practice of general physical examinations.
Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose-response relationship with MR-ARFI
Authors: Mohammadjavadi Morteza , Ash Ryan T. , Li Ningrui , Gaur Pooja , Kubanek Jan , Saenz Yamil , Glover Gary H. , Popelka Gerald R. , Norcia Anthoney M. , Pauly Kim Butts 
Published: November 2022

AbstractNeuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. The purpose of this study was to confirm that MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) in the intact large animal; and to study the impact on cortical brain oscillations. The LGN on one side was identified with T2-weighted MRI in sheep (all male, n = 9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm localization of the targeted area in the brain. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time–frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. The VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input. Sonication-associated microscopic displacements, as measured by MR-ARFI, correlated with the TUS-mediated suppression of visual evoked activity. TUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.
EEG analysis of the visual motion activated vection network in left- and right-handers
Authors: McAssey Michaela , Brandt Thomas , Dieterich Marianne 
Published: November 2022

AbstractVisually-induced self-motion perception (vection) relies on interaction of the visual and vestibular systems. Neuroimaging studies have identified a lateralization of the thalamo-cortical multisensory vestibular network, with left-handers exhibiting a dominance of the left hemisphere and right-handers exhibiting a dominance of the right hemisphere. Using electroencephalography (EEG), we compare the early processing of a vection-consistent visual motion stimulus against a vection-inconsistent stimulus, to investigate the temporal activation of the vection network by visual motion stimulation and the lateralization of these processes in left- versus right-handers. In both groups, vection-consistent stimulation evoked attenuated central event-related potentials (ERPs) in an early (160–220 ms) and a late (260–300 ms) time window. Differences in estimated source activity were found across visual, sensorimotor, and multisensory vestibular cortex in the early window, and were observed primarily in the posterior cingulate, retrosplenial cortex, and precuneus in the late window. Group comparisons revealed a larger ERP condition difference (i.e. vection-consistent stimulation minus vection-inconsistent stimulation) in left-handers, which was accompanied by group differences in the cingulate sulcus visual (CSv) area. Together, these results suggest that handedness may influence ERP responses and activity in area CSv during vection-consistent and vection-inconsistent visual motion stimulation.
Investigation on factors related to poor CPAP adherence using machine learning: a pilot study
Authors: Eguchi Kana , Yabuuchi Tsutomu , Nambu Masayuki , Takeyama Hirofumi , Azuma Shozo , Chin Kazuo , Kuroda Tomohiro 
Published: November 2022

AbstractTo improve patients’ adherence to continuous positive airway pressure (CPAP) therapy, this study aimed to clarify whether machine learning-based data analysis can identify the factors related to poor CPAP adherence (i.e., CPAP usage that does not reach four hours per day for five days a week). We developed a CPAP adherence prediction model using logistic regression and learn-to-rank machine learning with a pairwise approach. We then investigated adherence prediction performance targeting a 12-week period and the top ten factors correlating to poor CPAP adherence. The CPAP logs of 219 patients with obstructive sleep apnea (OSA) obtained from clinical treatment at Kyoto University Hospital were used. The highest adherence prediction accuracy obtained was an F1 score of 0.864. Out of the top ten factors obtained with the highest prediction accuracy, four were consistent with already-known clinical knowledge. The factors for better CPAP adherence indicate that air leakage should be avoided, mask pressure should be kept constant, and CPAP usage duration should be longer and kept constant. The results indicate that machine learning is an adequate method for investigating factors related to poor CPAP adherence.
Binding epitope for recognition of human TRPM4 channel by monoclonal antibody M4M
Authors: Wei Shunhui , Behn Julian , Poore Charlene Priscilla , Low See Wee , Nilius Bernd , Fan Hao , Liao Ping 
Published: November 2022

AbstractMouse monoclonal antibody M4M was recently designed to block human TRPM4 channel. The polypeptide for generating M4M is composed of peptide A1 between the transmembrane segment 5 (S5) and the pore, and a second peptide A2 between the pore and the transmembrane segment 6 (S6). Using peptide microarray, a 4-amino acid sequence EPGF within the A2 was identified to be the binding epitope for M4M. Substitution of EPGF with other amino acids greatly reduced binding affinity. Structural analysis of human TRPM4 structure indicates that EPGF is located externally to the channel pore. A1 is close to the EPGF binding epitope in space, albeit separated by a 37-amino acid peptide. Electrophysiological study reveals that M4M could block human TRPM4, but with no effect on rodent TRPM4 which shares a different amino acid sequence ERGS for the binding motif. Our results demonstrate that M4M is a specific inhibitor for human TRPM4.
Neural network ensemble model for prediction of erythrocyte sedimentation rate (ESR) using partial least squares regression
Authors: Lee Jaejin , Hong Hyeonji , Song Jae Min , Yeom Eunseop 
Published: November 2022

AbstractThe erythrocyte sedimentation rate (ESR) is a non-specific blood test for determining inflammatory conditions. However, the long measurement time (60 min) to obtain ESR is an obstacle for a prompt evaluation. In this study, to reduce the measurement time of ESR, deep neural networks (DNNs) were applied to the sedimentation tendency of blood samples. DNNs using multilayer perceptron (MLP), long short-term memory (LSTM), and gated recurrent unit (GRU) were assessed and compared to determine a suitable length of time for the input sequence. To avoid overfitting, a stacking ensemble learning was adopted, which combines multiple models by using a meta model. Four meta models were compared: mean, median, least absolute shrinkage and selection operator, and partial least squares regression (PLSR) schemes. From the empirical results, LSTM and GRU models have better prediction than MLP over sequence lengths of 5 to 20 min. The decrease in$$\overline{\mathrm{MAPE} }$$MAPE¯and$$\overline{\mathrm{RMSE} }$$RMSE¯of GRU and LSTM was attenuated after a sequence length of 15 min, so the input sequence length is determined as 15 min. In terms of the meta model, the statistical comparison suggests that GRU combined with PLSR (GRU–PLSR) is the best case. Then, the GRU–PLSR was tested for prediction of ESR data obtained from periodontitis patients to check its applicability to a specific disease. The Bland–Altman plot shows acceptable agreement between measured and predicted ESR values. Based on the results, the GRU–PLSR can predict ESR with improved performance within 15 min and has potential applicability to ESR data with inflammatory and non-inflammatory conditions.