bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Study of EMIC Waves and Related Proton Distributions Observed by the Arase Satellite
Authors: Jun C.‐W. , Miyoshi Y. , Nakamura S. , Shoji M. , Kitahara M. , Hori T. , Yue C. , Bortnik J. , Lyons L. , Min K. , Kasahara Y. , Tsuchiya F. , Kumamoto A. , Asamura K. , Shinohara I. , Matsuoka A. , Imajo S. , Yokota S. , Kasahara S. , Keika K.
Published: May 2023

We performed a statistical study of electromagnetic ion cyclotron (EMIC) wave distributions and their coupling with energetic protons in the inner magnetosphere using the Arase satellite data from May 2017 to December 2020. We investigated the energetic proton pitch‐angle distributions and partial thermal pressures associated with EMIC waves using inter‐calibrated proton data in the energy range of 30 eV/q–187 keV/q. With a cold plasma approximation, we computed the proton minimum resonance energies using the observed EMIC wave frequency and plasma density values. We found that the EMIC waves had left‐handed polarization near the magnetic equator close to the threshold of proton cyclotron instability, and propagated to higher latitudes along the field line with polarization reversal. H‐EMIC waves showed two peak occurrence regions in the morning and noon sectors at L = 7.5–9 outside the plasmasphere. The flux enhancements associated with morning side H‐EMIC waves appeared at E < 1 keV/q among all pitch angles, while H‐EMIC waves in the noon sector exhibited flux enhancement in field‐aligned directions at E = 1–100 keV/q. He‐EMIC waves showed a broad occurrence region from 12 to 20 magnetic local time at L = 5.5–8.5 inside the plasmasphere with strong flux enhancements at all pitch‐angle ranges at E = 1–100 keV/q. The proton minimum resonance energy using the obtained central frequency was consistent with the observed flux enhancements at different peak occurrence regions. We conclude that the free energy sources of EMIC waves in different geomagnetic environments drive various types of EMIC waves, and they interact with energetic protons at different energy ranges.
A Model Integrating Satellite‐Derived Shoreline Observations for Predicting Fine‐Scale Shoreline Response to Waves and Sea‐Level Rise Across Large Coastal Regions
Authors: Vitousek Sean , Vos Kilian , Splinter Kristen D. , Erikson Li , Barnard Patrick L.
Published: May 2023

Satellite‐derived shoreline observations combined with dynamic shoreline models enable fine‐scale predictions of coastal change across large spatiotemporal scales. Here, we present a satellite‐data‐assimilated, “littoral‐cell”‐based, ensemble Kalman‐filter shoreline model to predict coastal change and uncertainty due to waves, sea‐level rise (SLR), and other natural and anthropogenic processes. We apply the developed ensemble model to the entire California coastline (approximately 1,760 km), much of which is sparsely monitored with traditional survey methods (e.g., Lidar/GPS). Water‐level‐corrected, satellite‐derived shoreline observations (obtained from the CoastSat toolbox) offer a nearly unbiased representation of in situ surveyed shorelines (e.g., mean sea‐level elevation contours) at Ocean Beach, San Francisco. We demonstrate that model calibration with satellite observations during a 20‐year hindcast period (1995–2015) provides nearly equivalent model forecast accuracy during a validation period (2015–2020) compared to model calibration with monthly in situ observations at Ocean Beach. When comparing model‐predicted shoreline positions to satellite‐derived observations, the model achieves an accuracy of <10 m RMSE for nearly half of the entire California coastline for the validation period. The calibrated/validated model is then applied for multi‐decadal simulations of shoreline change due to projected wave and sea‐level conditions, while holding the model parameters fixed. By 2100, the model estimates that 24%–75% of California's beaches may become completely eroded due to SLR scenarios of 1.0–3.0 m, respectively. The satellite‐data‐assimilated modeling system presented here is generally applicable to a variety of coastal settings around the world owing to the global coverage of satellite imagery.
Analysis of Organic Matter Decomposition in the Salt Marshes of the Venice Lagoon (Italy) Using Standard Litter Bags
Authors: Puppin A. , Roner M. , Finotello A. , Ghinassi M. , Tommasini L. , Marani M. , D'Alpaos A.
Published: May 2023

Tidal salt marshes are widespread along the World's coasts, and are ecologically and economically important as they provide several valuable ecosystem services. In particular, their significant primary production, coupled with sustained vertical accretion rates, enables marshes to sequester and store large amounts of organic carbon and makes them one of the most carbon‐rich ecosystems on Earth. Organic carbon accumulation results from the balance between inputs, that is, organic matter produced by local plants or imported, and outputs through decomposition and erosion. Additionally, organic matter deposition actively contributes to marsh vertical accretion, thus critically affecting the resilience of marsh ecosystems to rising relative sea levels. A better understanding of organic‐matter dynamics in salt marshes is key to address salt‐marsh conservation issues and to elucidate marsh importance within the global carbon cycle. Toward this goal, we empirically derived rates of organic matter decomposition by burying 712 commercially available tea bags at different marshes in the microtidal Venice Lagoon (Italy), and by analyzing them following the Tea Bag Index protocol. We find values of the decomposition rate (k) and stabilization factor (S) equal to 0.012 ± 0.003 days−1 and 0.15 ± 0.063, respectively. Water temperature critically affects organic matter decomposition, enhancing decomposition rates by 8% per °C on average. We argue that, at least in the short term, the amount of undecomposed organic matter that actively contributes to carbon sequestration and marsh vertical accretion strongly depends on the initial organic matter quality, which is a function of marsh and vegetation characteristics.
Global Synthesis of Regional Holocene Hydroclimate Variability Using Proxy and Model Data
Authors: Hancock Christopher L. , McKay Nicholas P. , Erb Michael P. , Kaufman Darrell S. , Routson Cody R. , Ivanovic Ruza F. , Gregoire Lauren J. , Valdes Paul
Published: May 2023

Substantial changes in terrestrial hydroclimate during the Holocene are recorded in geological archives and simulated by computer models. To identify spatial and temporal patterns during the past 12 ka, proxy records sensitive to changing precipitation and effective moisture (precipitation minus evaporation) were compiled from across the globe (n = 813). Proxy composite timeseries were computed for 30 of the IPCC AR6 regions and compared to two full‐Holocene transient model simulations (TraCE‐21ka and HadCM3) and twelve mid‐Holocene CMIP6 simulations. We find that throughout Northern Hemisphere monsoon regions, proxy and model simulations indicate wetter‐than‐modern conditions during the early and mid‐Holocene while Southern Hemisphere monsoon regions were drier. This insolation driven trend toward modern values began approximately 6,000 years ago, and the clear agreement among proxy records and models may reflect the large magnitude of precipitation change and consistent atmospheric circulation forcing mechanism for these regions. In the midlatitudes, the pattern of change is less certain. Generally, proxy composites show a wetting trend throughout the Holocene for the northern midlatitudes, possibly due to strengthening westerlies from an increasing latitudinal temperature gradient. However, simulations indicate that the magnitude of change was relatively low, and for portions of North America, there is a proxy‐model disagreement. At high latitudes, hydroclimate is positively correlated with temperature in both proxies and models, consistent with projected wetting as temperatures rise. Overall, this large proxy database reveals a coherent pattern of hydroclimate variability despite the challenges associated with reconstructing hydroclimate fields.
PLEKHG5 is stabilized by HDAC2-related deacetylation and confers sorafenib resistance in hepatocellular carcinoma
Authors: Sha Yu , Pan Mingang , Chen Yunmeng , Qiao Liangjun , Zhou Hengyu , Liu Dina , Zhang Wenlu , Wang Kai , Huang Luyi , Tang Ni , Qiu Jianguo , Huang Ailong , Xia Jie
Published: May 2023

Sorafenib is the first FDA-approved first-line targeted drug for advanced HCC. However, resistance to sorafenib is frequently observed in clinical practice, and the molecular mechanism remains largely unknown. Here, we found that PLEKHG5 (pleckstrin homology and RhoGEF domain containing G5), a RhoGEF, was highly upregulated in sorafenib-resistant cells. PLEKHG5 overexpression activated Rac1/AKT/NF-κB signaling and reduced sensitivity to sorafenib in HCC cells, while knockdown of PLEKHG5 increased sorafenib sensitivity. The increased PLEKHG5 was related to its acetylation level and protein stability. Histone deacetylase 2 (HDAC2) was found to directly interact with PLEKHG5 to deacetylate its lysine sites within the PH domain and consequently maintain its stability. Moreover, knockout of HDAC2 (HDAC2 KO) or selective HDAC2 inhibition reduced PLEKHG5 protein levels and thereby enhanced the sensitivity of HCC to sorafenib in vitro and in vivo, while overexpression of PLEKHG5 in HDAC2 KO cells reduced the sensitivity to sorafenib. Our work showed a novel mechanism: HDAC2-mediated PLEKHG5 posttranslational modification maintains sorafenib resistance. This is a proof-of-concept study on targeting HDAC2 and PLEKHG5 in sorafenib-treated HCC patients as a new pharmaceutical intervention for advanced HCC.
Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Authors: Liu Huihui , Liu Hongchao , Wang Longhao , Song Lei , Jiang Guixian , Lu Qing , Yang Tao , Peng Hu , Cai Ruijie , Zhao Xingle , Zhao Ting , Wu Hao
Published: May 2023

Isoforms of a gene may contribute to diverse biological functions. In the cochlea, the repertoire of alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques and identified 236,012 transcripts, 126,612 of which were unannotated in the GENCODE database. Then we analyzed and verified the unannotated transcripts using RNA-seq, RT-PCR, Sanger sequencing, and MS-based proteomics approaches. To illustrate the importance of identifying spliced isoforms, we investigated otoferlin, a key protein involved in synaptic transmission in inner hair cells (IHCs). Upon deletion of the canonical otoferlin isoform, the identified short isoform is able to support normal hearing thresholds but with reduced sustained exocytosis of IHCs, and further revealed otoferlin functions in endocytic membrane retrieval that was not well-addressed previously. Furthermore, we found that otoferlin isoforms are associated with IHC functions and auditory phenotypes. This work expands our mechanistic understanding of auditory functions at the level of isoform resolution.
From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia
Authors: Saez-Ayala Magali , Hoffer Laurent , Abel Sébastien , Ben Yaala Khaoula , Sicard Benoit , Andrieu Guillaume P. , Latiri Mehdi , Davison Emma K. , Ciufolini Marco A. , Brémond Paul , Rebuffet Etienne , Roche Philippe , Derviaux Carine , Voisset Edwige , Montersino Camille , Castellano Remy , Collette Yves , Asnafi Vahid , Betzi Stéphane , Dubreuil Patrice , Combes Sébastien , Morelli Xavier
Published: May 2023

Cancer cells utilize the main de novo pathway and the alternative salvage pathway for deoxyribonucleotide biosynthesis to achieve adequate nucleotide pools. Deoxycytidine kinase is the rate-limiting enzyme of the salvage pathway and it has recently emerged as a target for anti-proliferative therapies for cancers where it is essential. Here, we present the development of a potent inhibitor applying an iterative multidisciplinary approach, which relies on computational design coupled with experimental evaluations. This strategy allows an acceleration of the hit-to-lead process by gradually implementing key chemical modifications to increase affinity and activity. Our lead compound, OR0642, is more than 1000 times more potent than its initial parent compound, masitinib, previously identified from a drug repositioning approach. OR0642 in combination with a physiological inhibitor of the de novo pathway doubled the survival rate in a human T-cell acute lymphoblastic leukemia patient-derived xenograft mouse model, demonstrating the proof-of-concept of this drug design strategy.
Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health
Authors: Daly James L. , Danson Chris M. , Lewis Philip A. , Zhao Lu , Riccardo Sara , Di Filippo Lucio , Cacchiarelli Davide , Lee Daehoon , Cross Stephen J. , Heesom Kate J. , Xiong Wen-Cheng , Ballabio Andrea , Edgar James R. , Cullen Peter J.
Published: May 2023

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify widespread changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide a holistic view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.
OsMADS17 simultaneously increases grain number and grain weight in rice
Authors: Li Yuanjie , Wu Sheng , Huang Yongyu , Ma Xin , Tan Lubin , Liu Fengxia , Lv Qiming , Zhu Zuofeng , Hu Meixia , Fu Yongcai , Zhang Kun , Gu Ping , Xie Daoxin , Sun Hongying , Sun Chuanqing
Published: May 2023

During the processes of rice domestication and improvement, a trade-off effect between grain number and grain weight was a major obstacle for increasing yield. Here, we identify a critical gene COG1, encoding the transcription factor OsMADS17, with a 65-bp deletion in the 5′ untranslated region (5′ UTR) presented in cultivated rice increasing grain number and grain weight simultaneously through decreasing mRNA translation efficiency. OsMADS17 controls grain yield by regulating multiple genes and that the interaction with one of them, OsAP2-39, has been characterized. Besides, the expression of OsMADS17 is regulated by OsMADS1 directly. It indicates that OsMADS1-OsMADS17-OsAP2-39 participates in the regulatory network controlling grain yield, and downregulation of OsMADS17 or OsAP2-39 expression can further improve grain yield by simultaneously increasing grain number and grain weight. Our findings provide insights into understanding the molecular basis co-regulating rice yield-related traits, and offer a strategy for breeding higher-yielding rice varieties.
Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics
Authors: Gao Junyi , Heintz Joerg , Mack Christina , Glass Lucas , Cross Adam , Sun Jimeng
Published: May 2023

In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 $${R}^{2}$$

R

2

and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.
Quantitative structured illumination microscopy via a physical model-based background filtering algorithm reveals actin dynamics
Authors: Mo Yanquan , Wang Kunhao , Li Liuju , Xing Shijia , Ye Shouhua , Wen Jiayuan , Duan Xinxin , Luo Ziying , Gou Wen , Chen Tongsheng , Zhang Yu-Hui , Guo Changliang , Fan Junchao , Chen Liangyi
Published: May 2023

Despite the prevalence of superresolution (SR) microscopy, quantitative live-cell SR imaging that maintains the completeness of delicate structures and the linearity of fluorescence signals remains an uncharted territory. Structured illumination microscopy (SIM) is the ideal tool for live-cell SR imaging. However, it suffers from an out-of-focus background that leads to reconstruction artifacts. Previous post hoc background suppression methods are prone to human bias, fail at densely labeled structures, and are nonlinear. Here, we propose a physical model-based Background Filtering method for living cell SR imaging combined with the 2D-SIM reconstruction procedure (BF-SIM). BF-SIM helps preserve intricate and weak structures down to sub-70 nm resolution while maintaining signal linearity, which allows for the discovery of dynamic actin structures that, to the best of our knowledge, have not been previously monitored.
Prehistoric population expansion in Central Asia promoted by the Altai Holocene Climatic Optimum
Authors: Xiang Lixiong , Huang Xiaozhong , Sun Mingjie , Panizzo Virginia N. , Huang Chong , Zheng Min , Chen Xuemei , Chen Fahu
Published: May 2023

How climate change in the middle to late Holocene has influenced the early human migrations in Central Asian Steppe remains poorly understood. To address this issue, we reconstructed a multiproxy-based Holocene climate history from the sediments of Kanas Lake and neighboring Tiewaike Lake in the southern Altai Mountains. The results show an exceptionally warm climate during ~6.5–3.6 kyr is indicated by the silicon isotope composition of diatom silica (δ30Sidiatom) and the biogenic silica (BSi) content. During 4.7-4.3 kyr, a peak in δ30Sidiatom reflects enhanced lake thermal stratification and periodic nutrient limitation as indicated by concomitant decreasing BSi content. Our geochemical results indicate a significantly warm and wet climate in the Altai Mountain region during 6.5–3.6 kyr, corresponding to the Altai Holocene Climatic Optimum (AHCO), which is critical for promoting prehistoric human population expansion and intensified cultural exchanges across the Central Asian steppe during the Bronze Age.
The COG1-OsSERL2 complex senses cold to trigger signaling network for chilling tolerance in japonica rice
Authors: Xia Changxuan , Liang Guohua , Chong Kang , Xu Yunyuan
Published: May 2023

Improvement of chilling tolerance is a key strategy to face potential menace from abnormal temperature in rice production, which depends on the signaling network triggered by receptors. However, little is known about the QTL genes encoding membrane complexes for sensing cold. Here, Chilling-tolerance inGengdao/japonica rice1 (COG1) is isolated from a chromosome segment substitution line containing a QTL (qCS11-jap) for chilling sensitivity. The major gene COG1 is found to confer chilling tolerance in japonica rice. In natural rice populations, only the haplogroup1 encodes a functional COG1. Evolutionary analysis show that COG1 originates from Chinese O. Rufipogon and is fixed in japonica rice during domestication. COG1, a membrane-localized LRR-RLP, targets and activates the kinase OsSERL2 in a cold-induced manner, promoting chilling tolerance. Furthermore, the cold signal transmitted by COG1-OsSERL2 activates OsMAPK3 in the cytoplasm. Our findings reveal a cold-sensing complex, which mediates signaling network for the chilling defense in rice.
Evidence against a temporal association between cerebrovascular disease and Alzheimer’s disease imaging biomarkers
Authors: Cogswell Petrice M. , Lundt Emily S. , Therneau Terry M. , Mester Carly T. , Wiste Heather J. , Graff-Radford Jonathan , Schwarz Christopher G. , Senjem Matthew L. , Gunter Jeffrey L. , Reid Robert I. , Przybelski Scott A. , Knopman David S. , Vemuri Prashanthi , Petersen Ronald C. , Jack Clifford R.
Published: May 2023

Whether a relationship exists between cerebrovascular disease and Alzheimer’s disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease processes may inform mechanistic associations. We investigate the relationship of disease trajectories of cerebrovascular disease (white matter hyperintensity, WMH, and fractional anisotropy, FA) and Alzheimer’s disease (amyloid and tau PET) biomarkers in 2406 Mayo Clinic Study of Aging and Mayo Alzheimer’s Disease Research Center participants using accelerated failure time models. The model assumes a common pattern of progression for each biomarker that is shifted earlier or later in time for each individual and represented by a per participant age adjustment. An individual’s amyloid and tau PET adjustments show very weak temporal association with WMH and FA adjustments (R = −0.07 to 0.07); early/late amyloid or tau timing explains <1% of the variation in WMH and FA adjustment. Earlier onset of amyloid is associated with earlier onset of tau (R = 0.57, R2 = 32%). These findings support a strong mechanistic relationship between amyloid and tau aggregation, but not between WMH or FA and amyloid or tau PET.
Computation-based regulation of excitonic effects in donor-acceptor covalent organic frameworks for enhanced photocatalysis
Authors: Qian Yunyang , Han Yulan , Zhang Xiyuan , Yang Ge , Zhang Guozhen , Jiang Hai-Long
Published: May 2023

The strong excitonic effects widely exist in polymer-semiconductors and the large exciton binding energy (Eb) seriously limits their photocatalysis. Herein, density functional theory (DFT) calculations are conducted to assess band alignment and charge transfer feature of potential donor-acceptor (D-A) covalent organic frameworks (COFs), using 1,3,5-tris(4-aminophenyl)triazine (TAPT) or 1,3,5-tris(4-aminophenyl)benzene (TAPB) as acceptors and tereph-thaldehydes functionalized diverse groups as donors. Given the discernable D-A interaction strengths in the D-A pairs, their Eb can be systematically regulated with minimum Eb in TAPT-OMe. Guided by these results, the corresponding D-A COFs are synthesized, where TAPT-OMe-COF possesses the best activity in photocatalytic H2 production and the activity trend of other COFs is associated with that of calculated Eb for the D-A pairs. In addition, further alkyne cycloaddition for the imine linkage in the COFs greatly improves the stability and the resulting TAPT-OMe-alkyne-COF with a substantially smaller Eb exhibits ~20 times higher activity than the parent COF.
Computational discovery of ultra-strong, stable, and lightweight refractory multi-principal element alloys. Part II: comprehensive ternary design and validation
Authors: Elder Kate L. M. , Berry Joel , Perron Aurélien , Bocklund Brandon , Shittu Jibril , Rietema Connor J. , Henderson Hunter B. , McCall Scott K. , McKeown Joseph T.
Published: May 2023

Here the discovery of refractory multi-principal element alloys (MPEAs) with high-temperature strength and stability is pursued within a constrained and application-relevant design space. A comprehensive approach is developed and applied to explore all 165 ternary systems in the Al-Ce-Fe-Hf-Mo-Nb-Ta-Ti-V-W-Zr family. A subset of ternary systems that contain large areas in composition–temperature space with high strength and robust BCC phase stability is found. Twelve sets of high-performing alloys are identified, each set optimized for one combination of phase constraint, optimization target, and temperature range. Preliminary mechanical tests support the viability of the method. This work highlights the importance of considering phase stability, exploring non-equiatomic regions of composition space, and applying application-relevant constraints. Parts I and II provide three down-selection techniques for identifying high-performing BCC refractory MPEAs, design guidelines, and many candidates predicted to have BCC phase stability and strengths 2–3 times higher than any reported to date.
Intertwined electronic and magnetic structure of the van-der-Waals antiferromagnet Fe2P2S6
Authors: Koitzsch A. , Klaproth T. , Selter S. , Shemerliuk Y. , Aswartham S. , Janson O. , Büchner B. , Knupfer M.
Published: May 2023

Many unusual and promising properties have been reported recently for the transition metal trichalcogenides of the type MPS3 (M = V, Mn, Fe, Ni ...), such as maintaining magnetic order to the atomically thin limit, ultra-sharp many-body excitons, metal-insulator transitions and, especially for Fe2P2S6, giant linear dichroism among others. Here we conduct a detailed investigation of the electronic structure of Fe2P2S6 using angle-resolved photoemission spectroscopy, q-dependent electron energy loss spectroscopy, optical spectroscopies and density functional theory. Fe2P2S6 is a Mott insulator with a gap of Egap ≈ 1.4 eV and zigzag antiferromagnetism below TN = 119 K. The low energy excitations are dominated by Fe 3d states. Large and sign-changing linear dichroism is observed. We provide a microscopic mechanism explaining key properties of the linear dichroism based on the correlated character of the electronic structure, thereby elucidating the nature of the spin-charge coupling in Fe2P2S6 and related materials.
Syntactic complexity and diversity of spontaneous speech production in schizophrenia spectrum and major depressive disorders
Authors: Schneider Katharina , Leinweber Katrin , Jamalabadi Hamidreza , Teutenberg Lea , Brosch Katharina , Pfarr Julia-Katharina , Thomas-Odenthal Florian , Usemann Paula , Wroblewski Adrian , Straube Benjamin , Alexander Nina , Nenadić Igor , Jansen Andreas , Krug Axel , Dannlowski Udo , Kircher Tilo , Nagels Arne , Stein Frederike
Published: May 2023

Syntax, the grammatical structure of sentences, is a fundamental aspect of language. It remains debated whether reduced syntactic complexity is unique to schizophrenia spectrum disorder (SSD) or whether it is also present in major depressive disorder (MDD). Furthermore, the association of syntax (including syntactic complexity and diversity) with language-related neuropsychology and psychopathological symptoms across disorders remains unclear. Thirty-four SSD patients and thirty-eight MDD patients diagnosed according to DSM-IV-TR as well as forty healthy controls (HC) were included and tasked with describing four pictures from the Thematic Apperception Test. We analyzed the produced speech regarding its syntax delineating measures for syntactic complexity (the total number of main clauses embedding subordinate clauses) and diversity (number of different types of complex sentences). We performed cluster analysis to identify clusters based on syntax and investigated associations of syntactic, to language-related neuropsychological (verbal fluency and verbal episodic memory), and psychopathological measures (positive and negative formal thought disorder) using network analyses. Syntax in SSD was significantly reduced in comparison to MDD and HC, whereas the comparison of HC and MDD revealed no significant differences. No associations were present between speech measures and current medication, duration and severity of illness, age or sex; the single association accounted for was education. A cluster analysis resulted in four clusters with different degrees of syntax across diagnoses. Subjects with less syntax exhibited pronounced positive and negative symptoms and displayed poorer performance in executive functioning, global functioning, and verbal episodic memory. All cluster-based networks indicated varying degrees of domain-specific and cross-domain connections. Measures of syntactic complexity were closely related while syntactic diversity appeared to be a separate node outside of the syntactic network. Cross-domain associations were more salient in more complex syntactic production.
The effect of prediction error on episodic memory encoding is modulated by the outcome of the predictions
Authors: Pupillo Francesco , Ortiz-Tudela Javier , Bruckner Rasmus , Shing Yee Lee
Published: May 2023

Expectations can lead to prediction errors of varying degrees depending on the extent to which the information encountered in the environment conforms with prior knowledge. While there is strong evidence on the computationally specific effects of such prediction errors on learning, relatively less evidence is available regarding their effects on episodic memory. Here, we had participants work on a task in which they learned context/object-category associations of different strengths based on the outcomes of their predictions. We then used a reinforcement learning model to derive subject-specific trial-to-trial estimates of prediction error at encoding and link it to subsequent recognition memory. Results showed that model-derived prediction errors at encoding influenced subsequent memory as a function of the outcome of participants’ predictions (correct vs. incorrect). When participants correctly predicted the object category, stronger prediction errors (as a consequence of weak expectations) led to enhanced memory. In contrast, when participants incorrectly predicted the object category, stronger prediction errors (as a consequence of strong expectations) led to impaired memory. These results highlight the important moderating role of choice outcome that may be related to interactions between the hippocampal and striatal dopaminergic systems.
Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study
Authors: Deutschmann Paul , Forth Jan-Hendrik , Sehl-Ewert Julia , Carrau Tessa , Viaplana Elisenda , Mancera Jose Carlos , Urniza Alicia , Beer Martin , Blome Sandra
Published: May 2023

African swine fever (ASF) has gained panzootic dimensions and commercial vaccines are still unavailable. Recently, a series of live attenuated vaccines has raised hope for an efficacious and safe vaccine, among them “ASFV-G-∆MGF”. We tested the latter in an in vivo reversion to virulence study in accordance with International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products guidelines. Upon forced animal passaging, a virus variant emerged that was associated with transient fever and an increased replication and shedding. However, all animals were healthy upon completion of the study and reversion to significant virulence was not observed. The genomic changes did not affect the recombination site but involved deletions and reorganizations in the terminal regions of the genome. Thus, our study underscores that in-depth safety characterization is needed for live ASF vaccines. For this particular candidate, additional studies should target long-term effects and transmission characteristics before thorough benefit-risk analysis can be carried out.
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
Authors: Bellaver Bruna , Povala Guilherme , Ferreira Pamela C. L. , Ferrari-Souza João Pedro , Leffa Douglas T. , Lussier Firoza Z. , Benedet Andréa L. , Ashton Nicholas J. , Triana-Baltzer Gallen , Kolb Hartmuth C. , Tissot Cécile , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Rahmouni Nesrine , Lopez Oscar L. , Tudorascu Dana L. , Villemagne Victor L. , Ikonomovic Milos D. , Gauthier Serge , Zimmer Eduardo R. , Zetterberg Henrik , Blennow Kaj , Aizenstein Howard J. , Klunk William E. , Snitz Beth E. , Maki Pauline , Thurston Rebecca C. , Cohen Ann D. , Ganguli Mary , Karikari Thomas K. , Rosa-Neto Pedro , Pascoal Tharick A.
Published: May 2023

An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast+individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Learning consistent subcellular landmarks to quantify changes in multiplexed protein maps
Authors: Spitzer Hannah , Berry Scott , Donoghoe Mark , Pelkmans Lucas , Theis Fabian J.
Published: May 2023

Highly multiplexed imaging holds enormous promise for understanding how spatial context shapes the activity of the genome and its products at multiple length scales. Here, we introduce a deep learning framework called CAMPA (Conditional Autoencoder for Multiplexed Pixel Analysis), which uses a conditional variational autoencoder to learn representations of molecular pixel profiles that are consistent across heterogeneous cell populations and experimental perturbations. Clustering these pixel-level representations identifies consistent subcellular landmarks, which can be quantitatively compared in terms of their size, shape, molecular composition and relative spatial organization. Using high-resolution multiplexed immunofluorescence, this reveals how subcellular organization changes upon perturbation of RNA synthesis, RNA processing or cell size, and uncovers links between the molecular composition of membraneless organelles and cell-to-cell variability in bulk RNA synthesis rates. By capturing interpretable cellular phenotypes, we anticipate that CAMPA will greatly accelerate the systematic mapping of multiscale atlases of biological organization to identify the rules by which context shapes physiology and disease.
SIMBA: single-cell embedding along with features
Authors: Chen Huidong , Ryu Jayoung , Vinyard Michael E. , Lerer Adam , Pinello Luca
Published: May 2023

Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability to explicitly model interactions between different feature types. Furthermore, these methods are tailored to specific tasks, as distinct single-cell problems are formulated differently. To address these shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells and their defining features, such as genes, chromatin-accessible regions and DNA sequences, into a common latent space. By leveraging the co-embedding of cells and features, SIMBA allows for the study of cellular heterogeneity, clustering-free marker discovery, gene regulation inference, batch effect removal and omics data integration. We show that SIMBA provides a single framework that allows diverse single-cell problems to be formulated in a unified way and thus simplifies the development of new analyses and extension to new single-cell modalities. SIMBA is implemented as a comprehensive Python library (https://simba-bio.readthedocs.io).
Postsynaptic synucleins mediate endocannabinoid signaling
Authors: Albarran Eddy , Sun Yue , Liu Yu , Raju Karthik , Dong Ao , Li Yulong , Wang Sui , Südhof Thomas C. , Ding Jun B.
Published: May 2023

Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, and yet little is understood about the release of endocannabinoids from postsynaptic compartments. Here we report an unexpected finding that endocannabinoid release requires synucleins, key contributors to Parkinson’s disease. We show that endocannabinoids are released postsynaptically by a synuclein-dependent and SNARE-dependent mechanism. Specifically, we found that synuclein deletion blocks endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wild-type but not of mutant α-synuclein. Whole-cell recordings and direct optical monitoring of endocannabinoid signaling suggest that the synuclein deletion specifically blocks endocannabinoid release. Given the presynaptic role of synucleins in regulating vesicle lifecycle, we hypothesize that endocannabinoids are released via a membrane interaction mechanism. Consistent with this hypothesis, postsynaptic expression of tetanus toxin light chain, which cleaves synaptobrevin SNAREs, also blocks endocannabinoid-dependent signaling. The unexpected finding that endocannabinoids are released via a synuclein-dependent mechanism is consistent with a general function of synucleins in membrane trafficking and adds a piece to the longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.
Gaidai-Xing reliability method validation for 10-MW floating wind turbines
Authors: Gaidai Oleg , Xing Yihan , Xu Jingxiang , Balakrishna Rajiv
Published: May 2023

In contrast to well-known bivariate statistical approach, which is known to properly forecast extreme response levels for two-dimensional systems, the research validates innovative structural reliability method, which is particularly appropriate for multi-dimensional structural responses. The disadvantage of dealing with large system dimensionality and cross-correlation across multiple dimensions is not a benefit of traditional dependability approaches that deal with time series. Since offshore constructions are built to handle extremely high wind and wave loads, understanding these severe stresses is essential, e.g. wind turbines should be built and operated with the least amount of inconvenience. In the first scenario, the blade root flapwise bending moment is examined, whereas in the second, the tower bottom fore-aft bending moment is examined. The FAST simulation program was utilized to generate the empirical bending moments for this investigation with the load instances activated at under-rated, rated, and above-rated speeds. The novel reliability approach, in contrast to conventional reliability methods, does not call for the study of a multi-dimensional reliability function in the case of numerical simulation. As demonstrated in this work, it is now possible to assess multi-degree-of-freedom nonlinear system failure probability, in the case when only limited system measurements are available.
Ultra-low-cost mechanical smartphone attachment for no-calibration blood pressure measurement
Authors: Xuan Yinan , Barry Colin , De Souza Jessica , Wen Jessica H. , Antipa Nick , Moore Alison A. , Wang Edward J.
Published: May 2023

We propose an ultra-low-cost at-home blood pressure monitor that leverages a plastic clip with a spring-loaded mechanism to enable a smartphone with a flash LED and camera to measure blood pressure. Our system, called BPClip, is based on the scientific premise of measuring oscillometry at the fingertip to measure blood pressure. To enable a smartphone to measure the pressure applied to the digital artery, a moveable pinhole projection moves closer to the camera as the user presses down on the clip with increased force. As a user presses on the device with increased force, the spring-loaded mechanism compresses. The size of the pinhole thus encodes the pressure applied to the finger. In conjunction, the brightness fluctuation of the pinhole projection correlates to the arterial pulse amplitude. By capturing the size and brightness of the pinhole projection with the built-in camera, the smartphone can measure a user’s blood pressure with only a low-cost, plastic clip and an app. Unlike prior approaches, this system does not require a blood pressure cuff measurement for a user-specific calibration compared to pulse transit time and pulse wave analysis based blood pressure monitoring solutions. Our solution also does not require specialized smartphone models with custom sensors. Our early feasibility finding demonstrates that in a validation study with N = 29 participants with systolic blood pressures ranging from 88 to 157 mmHg, the BPClip system can achieve a mean absolute error of 8.72 and 5.49 for systolic and diastolic blood pressure, respectively. In an estimated cost projection study, we demonstrate that in small-batch manufacturing of 1000 units, the material cost is an estimated $0.80, suggesting that at full-scale production, our proposed BPClip concept can be produced at very low cost compared to existing cuff-based monitors for at-home blood pressure management.
Oil tanker under ice loadings
Authors: Gaidai Oleg , Yan Ping , Xing Yihan , Xu Jingxiang , Zhang Fuxi , Wu Yu
Published: May 2023

As a result of global warming, the area of the polar pack ice is diminishing, making merchant travel more practical. Even if Arctic ice thickness reduced in the summer, fractured ice is still presenting operational risks to the future navigation. The intricate process of ship-ice interaction includes stochastic ice loading on the vessel hull. In order to properly construct a vessel, the severe bow forces that arise must be accurately anticipated using statistical extrapolation techniques. This study examines the severe bow forces that an oil tanker encounters when sailing in the Arctic Ocean. Two stages are taken in the analysis. Then, using the FEM program ANSYS/LS-DYNA, the oil tanker bow force distribution is estimated. Second, in order to estimate the bow force levels connected with extended return periods, the average conditional exceedance rate approach is used to anticipate severe bow forces. The vessel’s itinerary was planned to take advantage of the weaker ice. As a result, the Arctic Ocean passage took a meandering route rather than a linear one. As a result, the ship route data that was investigated was inaccurate with regard to the ice thickness data encountered by a vessel yet skewed with regard to the ice thickness distribution in the region. This research intends to demonstrate the effective application of an exact reliability approach to an oil tanker with severe bow forces on a particular route.
Application of diffusion weighted multiple boli ASL to a murine model of human African trypanosomiasis
Authors: Paterson Samantha , Vallatos Antoine , Rodgers Jean , Holmes William M.
Published: May 2023

Human African Trypanosomiasis (HAT) is a parasitic disease originating in sub-Saharan Africa. There is limited information about the changes in the blood brain barrier (BBB) during this infection. This study is the first to apply diffusion weighted ASL (DWASL) to examine changes in BBB impairment. No significant changes in water exchange across the BBB were found during the infection, even when a loss of barrier integrity was seen using Contrast Enhanced MRI (Gd-DTPA) during the late stage of the disease. Furthermore, using multiple boli ASL (mbASL), changes in cerebral blood flow (CBF) were found during the course of infection. Overall, this study highlights the need for further study of the BBB during HAT infection to understand the complex mechanisms behind impairment.
Identification of prognostic hub genes and therapeutic targets for selenium deficiency in chicks model through transcriptome profiling
Authors: Lingamgunta Lakshman Kumar , Aloor Bindu Prasuna , Dasari Sreenivasulu , Ramakrishnan Ranjani , Botlagunta Mahendran , Madikonda Ashok Kumar , Gopal Shankar , Sade Ankanna
Published: May 2023

Selenium deficiency is a prevalent micronutrient deficiency that poses a major health concern worldwide. This study aimed to shed light on the molecular mechanisms underlying selenium deficiency using a chick model. Chickens were divided into control and selenium deficient groups. Plasma samples were collected to measure selenium concentration and transcriptome analyse were performed on oviduct samples. The results showed that selenium deficiency led to a significant reduction in plasma selenium levels and altered the expression of 10,266 differentially expressed genes (DEGs). These DEGs primarily regulated signal transduction and cell motility. The molecular function includes GTPase regulatory activity, and KEGG pathway analysis showed that they were mainly involved in the signal transduction. By using Cytoscape and CancerGeneNet tool, we identified 8 modules and 10 hub genes (FRK, JUN, PTPRC, ACTA2, MST1R, SDC4, SDC1, CXCL12, MX1 and EZR) associated with receptor tyrosine kinase pathway, Wnt and mTOR signaling pathways that may be closely related to cancer. These hub genes could be served as precise diagnostic and prognostic candidate biomarkers of selenium deficiency and potential targets for treatment strategies in both animals and humans. This study sheds light on the molecular basis of selenium deficiency and its potential impact on public health.
Dephasing by optical phonons in GaN defect single-photon emitters
Authors: Geng Yifei , Luo Jialun , van Deurzen Len , Xing Huili , Jena Debdeep , Fuchs Gregory David , Rana Farhan
Published: May 2023

Single-photon defect emitters (SPEs), especially those with magnetically and optically addressable spin states, in technologically mature wide bandgap semiconductors are attractive for realizing integrated platforms for quantum applications. Broadening of the zero phonon line (ZPL) caused by dephasing in solid state SPEs limits the indistinguishability of the emitted photons. Dephasing also limits the use of defect states in quantum information processing, sensing, and metrology. In most defect emitters, such as those in SiC and diamond, interaction with low-energy acoustic phonons determines the temperature dependence of the dephasing rate and the resulting broadening of the ZPL with the temperature obeys a power law. GaN hosts bright and stable single-photon emitters in the 600–700 nm wavelength range with strong ZPLs even at room temperature. In this work, we study the temperature dependence of the ZPL spectra of GaN SPEs integrated with solid immersion lenses with the goal of understanding the relevant dephasing mechanisms. At temperatures below ~ 50 K, the ZPL lineshape is found to be Gaussian and the ZPL linewidth is temperature independent and dominated by spectral diffusion. Above ~ 50 K, the linewidth increases monotonically with the temperature and the lineshape evolves into a Lorentzian. Quite remarkably, the temperature dependence of the linewidth does not follow a power law. We propose a model in which dephasing caused by absorption/emission of optical phonons in an elastic Raman process determines the temperature dependence of the lineshape and the linewidth. Our model explains the temperature dependence of the ZPL linewidth and lineshape in the entire 10–270 K temperature range explored in this work. The ~ 19 meV optical phonon energy extracted by fitting the model to the data matches remarkably well the ~ 18 meV zone center energy of the lowest optical phonon band ($$E_{2}(low)$$E2(low)) in GaN. Our work sheds light on the mechanisms responsible for linewidth broadening in GaN SPEs. Since a low energy optical phonon band ($$E_{2}(low)$$E2(low)) is a feature of most group III–V nitrides with a wurtzite crystal structure, including hBN and AlN, we expect our proposed mechanism to play an important role in defect emitters in these materials as well.