bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Triage and Management in Earthquake-Related Injuries: The SAFE-QUAKE Scoring System for Predicting Dialysis Requirements
Authors: Yılmaz Sarper , Cetinkaya Remzi , Ozel Mehmet , Tatliparmak Ali Cankut , Ak Rohat
Published: October 2023

Objectives:

Identifying early predictors of dialysis requirements in earthquake-related injuries is crucial for optimal resource allocation and timely intervention. This study aimed to develop a predictive scoring system, named SAFE-QUAKE (Seismic Assessment of Kidney Function to Rule Out Dialysis Requirement), to identify patients at high risk of developing acute kidney injury (AKI) and requiring dialysis.

Methods:

A retrospective analysis was conducted on a cohort of 205 patients presenting with earthquake-related injuries. Patients were divided into two groups based on their need for dialysis: the no dialysis group (n = 170) and the dialysis group (n = 35). Demographic, clinical, and laboratory data were collected and compared between the two groups to identify significant predictors of dialysis requirements. The parameters that would form the score were determined by conducting an importance analysis using artificial neural networks (ANNs) to identify parameters that exhibited statistically significant differences in univariate analysis.

Results:

The dialysis group had a significantly longer median duration of being trapped under debris (48 hours) compared to the no dialysis group (eight hours). Blood gas and laboratory analyses revealed significant differences in pH levels, lactate values, creatinine levels, lactate dehydrogenase (LDH) levels, and aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio between the two groups. Based on these findings, the SAFE-QUAKE rule-out scoring system was developed, incorporating entrapment duration (<45 hours), pH levels (>7.31), creatinine levels (<2mg/dL), LDH levels (<1600mg/dL), and the AST-to-ALT ratio (<2.4) as key predictors of dialysis requirements. This score included 139 patients, and among them, only one patient required dialysis, resulting in a negative predictive value of 99.29%.

Conclusions:

The SAFE-QUAKE scoring system demonstrated a high negative predictive value of 99.29% in ruling out the need for dialysis among earthquake-related injury cases. This scoring system offers a practical approach for health care providers to identify patients at high risk of developing AKI and requiring dialysis in earthquake-affected regions.
Making Beethoven Black: The New Negro Movement, Black Internationalism, and the Rewriting of Music History
Authors: THURMAN KIRA
Published: October 2023

While the idea that Beethoven had African ancestry became popular in the 1960s during the Civil Rights struggle in the United States, its conception arose during an earlier moment: the global New Negro movement of the 1920s. Appearing in newspaper columns, music journals, and essays, Black American writings on Beethoven challenged white musicians’ claims to the canon of Bach, Beethoven, and Brahms. This article argues that the project of making Beethoven Black belonged to a greater and more ambitious endeavour to rewrite Western music history. Black musicologists sought to globalize the Western canon, and in so doing, critique its grand narratives. Locating Black musical idioms in eighteenth-century piano sonatas or conducting archival research on Black European figures such as George Bridgetower, their music histories challenged readers to re-examine just who, exactly, had contributed to the project of cultural modernity and on what grounds.
The 8‐Year Solar Cycle During the Maunder Minimum
Authors: Yan Limei , He Fei , Yue Xinan , Wei Yong , Wang Yuqi , Chen Si , Fan Kai , Tian Hui , He Jiansen , Zong Qiugang , Xia Lidong
Published: October 2023

The presence of grand minima, characterized by significantly reduced solar and stellar activity, brings a challenge to the understanding of solar and stellar dynamo. The Maunder Minimum (1645–1715 AD) is a representative grand solar minimum. The cyclic variation of solar activity, especially the cycle length during this period, is critical to understand the solar dynamo but remains unknown. By analyzing the variations in solar activity‐related equatorial auroras recorded in Korean historical books in the vicinity of a low‐intensity paleo‐West Pacific geomagnetic anomaly, we find clear evidence of an 8‐year solar cycle rather than the normal 11‐year cycle during the Maunder Minimum. This result provides a key constraint on solar dynamo models and the generation mechanism of grand solar minima.
The Spatial‐Temporal Dimension of Oncological Prevalence and Mortality in Romania
Authors: Peptenatu D. , Nedelcu I. D. , Pop C. S. , Simion A. G. , Furtunescu F. , Burcea M. , Andronache I. , Radulovic M. , Jelinek H. F. , Ahammer H. , Gruia A. K. , Grecu A. , Popa M. C. , Militaru V. , Drăghici C. C. , Pintilii R. D.
Published: October 2023

The objective of this study was to identify spatial disparities in the distribution of cancer hotspots within Romania. Additionally, the research aimed to track prevailing trends in cancer prevalence and mortality according to a cancer type. The study covered the timeframe between 2008 and 2017, examining all 3,181 territorial administrative units. The analysis of spatial distribution relied on two key parameters. The first parameter, persistence, measured the duration for which cancer prevalence exceeded the 75th percentile threshold. Cancer prevalence refers to the total number of individuals in a population who have been diagnosed with cancer at a specific time point, including both newly diagnosed cases (occurrence) and existing cases. The second parameter, the time continuity of persistence, calculated the consecutive months during which cancer prevalence consistently surpassed the 75th percentile threshold. Notably, persistence of elevated values was also evident in lowland regions, devoid of any discernible direct connection to environmental conditions. In conclusion, this work bears substantial relevance to regional health policies, by aiding in the formulation of prevention strategies, while also fostering a deeper comprehension of the socioeconomic and environmental factors contributing to cancer.
Resolving Moving Heliospheric Structures Using Interplanetary Scintillation Observations With the Murchison Widefield Array
Authors: Waszewski A. , Morgan J. S. , Chhetri R. , Ekers R. , Cheung M. C. M. , Bhat N. D. R. , Johnston‐Hollitt M.
Published: October 2023

We have conducted a blind search in 49 consecutive days of interplanetary scintillation observations made by the Murchison Widefield Array from mid‐2019, with overlapping daily observations approximately East and South‐East of the Sun at an elongation of ∼30° and a field of view of 30°. These observations detect an unprecedented density of sources. In spite of these observations being taken at sunspot minimum, this search has revealed several interesting transitory features characterized by elevated scintillation levels. One solar wind enhancement is captured in two observations several hours apart, allowing its radial movement away from the Sun to be measured. We present here a methodology for measuring the plane‐of‐sky velocity for the moving heliospheric structure. The plane‐of‐sky velocity was inferred as 0.66 ± 0.147 hr−1, or 480 ± 106 kms−1 assuming a distance of 1AU. After cross‐referencing our observed structure with multiple catalogs of heliospheric events, we propose that the likely source of our observed structure is a stream‐interaction region originating from a low‐latitude coronal hole. This work demonstrates the power of widefield interplanetary scintillation observations to capture detailed features in the heliosphere which are otherwise unresolvable and go undetected.
Mitochondrial proteins encoded by the 22q11.2 neurodevelopmental locus regulate neural stem and progenitor cell proliferation
Authors: Campbell Philip D. , Lee Isaiah , Thyme Summer , Granato Michael
Published: October 2023

Microdeletion of a 3Mb region encompassing 45 protein-coding genes at chromosome 22q11.2 (22q11.2DS) predisposes individuals to multiple neurodevelopmental disorders and is one of the greatest genetic risk factors for schizophrenia. Defective mitochondrial function has been hypothesized to contribute to 22q11.2DS pathogenesis; however, which of the six mitochondrial genes contribute to neurodevelopmental phenotypes and their underlying mechanisms remain unresolved. To systematically test 22q11.2DS genes for functional roles in neurodevelopment and behavior, we generated genetic mutants for each of the 37 conserved zebrafish orthologs and performed high throughput behavioral phenotyping using seven behavioral assays. Through this unbiased approach, we identified five single-gene mutants with partially overlapping behavioral phenotypes. Two of these genes,mrpl40andprodha, encode for mitochondrial proteins and, similar to what we observed inmrpl40andprodhamutants, pharmacologic inhibition of mitochondrial function during development results in microcephaly. Single mutant analysis shows that bothmrpl40andprodhamutants display aberrant neural stem and progenitor cell proliferation, with each gene regulating distinct cell populations. Finally, double mutants for bothmrpl40andprodhadisplay aggravated behavioral phenotypes and neural stem and progenitor cell analysis reveals a previously unrecognized partially redundant role formrpl40andprodhain regulating radial glia-like cell proliferation. Combined, our results demonstrate a critical role for mitochondrial function in neural stem and progenitor cell populations in the developing vertebrate brain and provide compelling evidence that mitochondrial dysfunction during neurodevelopment is linked to brain volume and behavioral phenotypes observed in models of 22q11.2DS.
Whole-genome sequencing analysis of suicide deaths integrating brain-regulatory eQTLs data to identify risk loci and genes
Authors: Han Seonggyun , DiBlasi Emily , Monson Eric T. , Shabalin Andrey , Ferris Elliott , Chen Danli , Fraser Alison , Yu Zhe , Staley Michael , Callor W. Brandon , Christensen Erik D. , Crockett David K. , Li Qingqin S. , Willour Virginia , Bakian Amanda V. , Keeshin Brooks , Docherty Anna R. , Eilbeck Karen , Coon Hilary
Published: October 2023

Recent large-scale genome-wide association studies (GWAS) have started to identify potential genetic risk loci associated with risk of suicide; however, a large portion of suicide-associated genetic factors affecting gene expression remain elusive. Dysregulated gene expression, not assessed by GWAS, may play a significant role in increasing the risk of suicide death. We performed the first comprehensive genomic association analysis prioritizing brain expression quantitative trait loci (eQTLs) within regulatory regions in suicide deaths from the Utah Suicide Genetic Risk Study (USGRS). 440,324 brain-regulatory eQTLs were obtained by integrating brain eQTLs, histone modification ChIP-seq, ATAC-seq, DNase-seq, and Hi-C results from publicly available data. Subsequent genomic analyses were conducted in whole-genome sequencing (WGS) data from 986 suicide deaths of non-Finnish European (NFE) ancestry and 415 ancestrally matched controls. Additional independent USGRS suicide deaths with genotyping array data (n = 4657) and controls from the Genome Aggregation Database were explored for WGS result replication. One significant eQTL locus, rs926308 (p = 3.24e−06), was identified. The rs926308-T is associated with lower expression of RFPL3S, a gene important for neocortex development and implicated in arousal. Gene-based analyses performed using Sherlock Bayesian statistical integrative analysis also detected 20 genes with expression changes that may contribute to suicide risk. From analyzing publicly available transcriptomic data, ten of these genes have previous evidence of differential expression in suicide death or in psychiatric disorders that may be associated with suicide, including schizophrenia and autism (ZNF501, ZNF502, CNN3, IGF1R, KLHL36, NBL1, PDCD6IP, SNX19, BCAP29, and ARSA). Electronic health records (EHR) data was further merged to evaluate if there were clinically relevant subsets of suicide deaths associated with genetic variants. In summary, our study identified one risk locus and ten genes associated with suicide risk via gene expression, providing new insight into possible genetic and molecular mechanisms leading to suicide.
The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control
Authors: Deng Jinhai , Pan Teng , Liu Zaoqu , McCarthy Caitlin , Vicencio Jose M. , Cao Lulu , Alfano Giovanna , Suwaidan Ali Abdulnabi , Yin Mingzhu , Beatson Richard , Ng Tony
Published: October 2023

Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from regulating glucose and lipid metabolism, to cell cycle arrest and inflammation. Its expression is increased by stressors commonly found in neoplastic cells and the wider tumor microenvironment (TME), and, as such, TXNIP has been extensively studied in cancers. In this review, we evaluate the current literature regarding the regulation and the function of TXNIP, highlighting its emerging role in modulating signaling between different cell types within the TME. We then assess current and future translational opportunities and the associated challenges in this area. An improved understanding of the functions and mechanisms of TXNIP in cancers may enhance its suitability as a therapeutic target.
Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
Authors: Jin Yongcheng , Mikhailova Ellina , Lei Ming , Cowley Sally A. , Sun Tianyi , Yang Xingyun , Zhang Yujia , Liu Kaili , Catarino da Silva Daniel , Campos Soares Luana , Bandiera Sara , Szele Francis G. , Molnár Zoltán , Zhou Linna , Bayley Hagan
Published: October 2023

Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient’s own induced pluripotent stem cells.
Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera
Authors: Hutchinson Geoffrey B. , Abiona Olubukola M. , Ziwawo Cynthia T. , Werner Anne P. , Ellis Daniel , Tsybovsky Yaroslav , Leist Sarah R. , Palandjian Charis , West Ande , Fritch Ethan J. , Wang Nianshuang , Wrapp Daniel , Boyoglu-Barnum Seyhan , Ueda George , Baker David , Kanekiyo Masaru , McLellan Jason S. , Baric Ralph S. , King Neil P. , Graham Barney S. , Corbett-Helaire Kizzmekia S.
Published: October 2023

Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor binding domain. However, targeting conserved non-RBD epitopes could limit the potential for antigenic escape. To explore new potential targets, we engineered protein nanoparticles displaying coronavirus prefusion-stabilized spike (CoV_S-2P) trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in female mice. Monotypic SARS-1 nanoparticles elicit cross-neutralizing antibodies against MERS-CoV and protect against MERS-CoV challenge. MERS and SARS nanoparticles elicit S1-focused antibodies, revealing a conserved site on the S N-terminal domain. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicit antibody responses to distant cross-group antigens and protect male and female mice against MERS-CoV challenge. Our findings will inform further efforts toward the development of pan-coronavirus vaccines.
Structure of the ceramide-bound SPOTS complex
Authors: Schäfer Jan-Hannes , Körner Carolin , Esch Bianca M. , Limar Sergej , Parey Kristian , Walter Stefan , Januliene Dovile , Moeller Arne , Fröhlich Florian
Published: October 2023

Sphingolipids are structural membrane components that also function in cellular stress responses. The serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in sphingolipid biogenesis. Its activity is tightly regulated through multiple binding partners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phosphate (PI4P) phosphatase Sac1. The structural organization and regulatory mechanisms of this complex are not yet understood. Here, we report the high-resolution cryo-EM structures of the yeast SPT in complex with Tsc3 and Orm1 (SPOT) as dimers and monomers and a monomeric complex further carrying Sac1 (SPOTS). In all complexes, the tight interaction of the downstream metabolite ceramide and Orm1 reveals the ceramide-dependent inhibition. Additionally, observation of ceramide and ergosterol binding suggests a co-regulation of sphingolipid biogenesis and sterol metabolism within the SPOTS complex.
Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress
Authors: Wang Wenjun , Tan Junyang , Liu Xiaomin , Guo Wenqi , Li Mengmeng , Liu Xinjie , Liu Yanyan , Dai Wenyu , Hu Liubing , Wang Yimin , Lu Qiuxia , Lee Wen Xing , Tang Hong-Wen , Zhou Qinghua
Published: October 2023

Endonuclease G (ENDOG), a nuclear-encoded mitochondrial intermembrane space protein, is well known to be translocated into the nucleus during apoptosis. Recent studies have shown that ENDOG might enter the mitochondrial matrix to regulate mitochondrial genome cleavage and replication. However, little is known about the role of ENDOG in the cytosol. Our previous work showed that cytoplasmic ENDOG competitively binds with 14-3-3γ, which released TSC2 to repress mTORC1 signaling and induce autophagy. Here, we demonstrate that cytoplasmic ENDOG could also release Rictor from 14-3-3γ to activate the mTORC2-AKT-ACLY axis, resulting in acetyl-CoA production. Importantly, we observe that ENDOG could translocate to the ER, bind with Bip, and release IRE1a/PERK to activate the endoplasmic reticulum stress response, promoting lipid synthesis. Taken together, we demonstrate that loss of ENDOG suppresses acetyl-CoA production and lipid synthesis, along with reducing endoplasmic reticulum stress, which eventually alleviates high-fat diet-induced nonalcoholic fatty liver disease in female mice.
Visualizing moiré ferroelectricity via plasmons and nano-photocurrent in graphene/twisted-WSe2 structures
Authors: Zhang Shuai , Liu Yang , Sun Zhiyuan , Chen Xinzhong , Li Baichang , Moore S. L. , Liu Song , Wang Zhiying , Rossi S. E. , Jing Ran , Fonseca Jordan , Yang Birui , Shao Yinming , Huang Chun-Ying , Handa Taketo , Xiong Lin , Fu Matthew , Pan Tsai-Chun , Halbertal Dorri , Xu Xinyi , Zheng Wenjun , Schuck P. J. , Pasupathy A. N. , Dean C. R. , Zhu Xiaoyang , Cobden David H. , Xu Xiaodong , Liu Mengkun , Fogler M. M. , Hone James C. , Basov D. N.
Published: October 2023

Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.
Myoglobin-loaded gadolinium nanotexaphyrins for oxygen synergy and imaging-guided radiosensitization therapy
Authors: Ma Xiaotu , Liang Xiaolong , Yao Meinan , Gao Yu , Luo Qi , Li Xiaoda , Yu Yue , Sun Yining , Cheng Miffy H. Y. , Chen Juan , Zheng Gang , Shi Jiyun , Wang Fan
Published: October 2023

Gadolinium (Gd3+)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks “Gd-Tex-lipids” to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O2 concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd3+, the versatile Mb@Gd-NTs can also chelate 177Lu3+ (Mb@177Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This “one-for-all” nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy.
PAM-flexible genome editing with an engineered chimeric Cas9
Authors: Zhao Lin , Koseki Sabrina R. T. , Silverstein Rachel A. , Amrani Nadia , Peng Christina , Kramme Christian , Savic Natasha , Pacesa Martin , Rodríguez Tomás C. , Stan Teodora , Tysinger Emma , Hong Lauren , Yudistyra Vivian , Ponnapati Manvitha R. , Jacobson Joseph M. , Church George M. , Jakimo Noah , Truant Ray , Jinek Martin , Kleinstiver Benjamin P. , Sontheimer Erik J. , Chatterjee Pranam
Published: October 2023

CRISPR enzymes require a defined protospacer adjacent motif (PAM) flanking a guide RNA-programmed target site, limiting their sequence accessibility for robust genome editing applications. In this study, we recombine the PAM-interacting domain of SpRY, a broad-targeting Cas9 possessing an NRN > NYN (R = A or G, Y = C or T) PAM preference, with the N-terminus of Sc + +, a Cas9 with simultaneously broad, efficient, and accurate NNG editing capabilities, to generate a chimeric enzyme with highly flexible PAM preference: SpRYc. We demonstrate that SpRYc leverages properties of both enzymes to specifically edit diverse PAMs and disease-related loci for potential therapeutic applications. In total, the approaches to generate SpRYc, coupled with its robust flexibility, highlight the power of integrative protein design for Cas9 engineering and motivate downstream editing applications that require precise genomic positioning.
Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu
Authors: Poudyal Manisha , Patel Komal , Gadhe Laxmikant , Sawner Ajay Singh , Kadu Pradeep , Datta Debalina , Mukherjee Semanti , Ray Soumik , Navalkar Ambuja , Maiti Siddhartha , Chatterjee Debdeep , Devi Jyoti , Bera Riya , Gahlot Nitisha , Joseph Jennifer , Padinhateeri Ranjith , Maji Samir K.
Published: October 2023

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological phenomenon underlying the sequestration of macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides but with distinct phase regimes irrespective of their sequence and structure. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study in the presence and absence of molecular crowder, polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase regimes and intermolecular interactions. We further demonstrated that electrostatic, hydrophobic, and H-bonding or a combination of such intermolecular interactions plays a crucial role in individual protein/peptide LLPS.
TerC proteins function during protein secretion to metalate exoenzymes
Authors: He Bixi , Sachla Ankita J. , Helmann John D.
Published: October 2023

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein export and a greatly reduced level of manganese (Mn) in the secreted proteome. MeeF and MeeY copurify with proteins of the general secretory pathway, and in their absence the FtsH membrane protease is essential for viability. MeeF and MeeY are also required for efficient function of the Mn2+-dependent lipoteichoic acid synthase (LtaS), a membrane-localized enzyme with an extracytoplasmic active site. Thus, MeeF and MeeY, representative of the widely conserved TerC family of membrane transporters, function in the co-translocational metalation of Mn2+-dependent membrane and extracellular enzymes.
Alternative splicing in lung influences COVID-19 severity and respiratory diseases
Authors: Nakanishi Tomoko , Willett Julian , Farjoun Yossi , Allen Richard J. , Guillen-Guio Beatriz , Adra Darin , Zhou Sirui , Richards J. Brent
Published: October 2023

Alternative splicing generates functional diversity in isoforms, impacting immune response to infection. Here, we evaluate the causal role of alternative splicing in COVID-19 severity and susceptibility by applying two-sample Mendelian randomization to cis-splicing quantitative trait loci and the results from COVID-19 Host Genetics Initiative. We identify that alternative splicing in lung, rather than total expression of OAS1, ATP11A, DPP9 and NPNT, is associated with COVID-19 severity. MUC1 and PMF1 splicing is associated with COVID-19 susceptibility. Colocalization analyses support a shared genetic mechanism between COVID-19 severity with idiopathic pulmonary fibrosis at the ATP11A and DPP9 loci, and with chronic obstructive lung diseases at the NPNT locus. Last, we show that ATP11A, DPP9, NPNT, and MUC1 are highly expressed in lung alveolar epithelial cells, both in COVID-19 uninfected and infected samples. These findings clarify the importance of alternative splicing in lung for COVID-19 and respiratory diseases, providing isoform-based targets for drug discovery.
Global land subsidence mapping reveals widespread loss of aquifer storage capacity
Authors: Hasan Md Fahim , Smith Ryan , Vajedian Sanaz , Pommerenke Rahel , Majumdar Sayantan
Published: October 2023

Groundwater overdraft gives rise to multiple adverse impacts including land subsidence and permanent groundwater storage loss. Existing methods are unable to characterize groundwater storage loss at the global scale with sufficient resolution to be relevant for local studies. Here we explore the interrelation between groundwater stress, aquifer depletion, and land subsidence using remote sensing and model-based datasets with a machine learning approach. The developed model predicts global land subsidence magnitude at high spatial resolution (~2 km), provides a first-order estimate of aquifer storage loss due to consolidation of ~17 km3/year globally, and quantifies key drivers of subsidence. Roughly 73% of the mapped subsidence occurs over cropland and urban areas, highlighting the need for sustainable groundwater management practices over these areas. The results of this study aid in assessing the spatial extents of subsidence in known subsiding areas, and in locating unknown groundwater stressed regions.
Open-loop analog programmable electrochemical memory array
Authors: Chen Peng , Liu Fenghao , Lin Peng , Li Peihong , Xiao Yu , Zhang Bihua , Pan Gang
Published: October 2023

Emerging memories have been developed as new physical infrastructures for hosting neural networks owing to their low-power analog computing characteristics. However, accurately and efficiently programming devices in an analog-valued array is still largely limited by the intrinsic physical non-idealities of the devices, thus hampering their applications in in-situ training of neural networks. Here, we demonstrate a passive electrochemical memory (ECRAM) array with many important characteristics necessary for accurate analog programming. Different image patterns can be open-loop and serially programmed into our ECRAM array, achieving high programming accuracies without any feedback adjustments. The excellent open-loop analog programmability has led us to in-situ train a bilayer neural network and reached software-like classification accuracy of 99.4% to detect poisonous mushrooms. The training capability is further studied in simulation for large-scale neural networks such as VGG-8. Our results present a new solution for implementing learning functions in an artificial intelligence hardware using emerging memories.
Incentive based emergency demand response effectively reduces peak load during heatwave without harm to vulnerable groups
Authors: Wang Zhaohua , Lu Bin , Wang Bo , Qiu Yueming , Shi Han , Zhang Bin , Li Jingyun , Li Hao , Zhao Wenhui
Published: October 2023

The incentive-based emergency demand response measure serves as an important regulatory tool during energy system operations. However, whether people will sacrifice comfort to respond to it during heatwave and what the effect on heat vulnerable populations will be are still unclear. A large-scale emergency demand response pilot involving 205,129 households was conducted in southwestern China during continuous extreme high temperatures in summer. We found that the incentive-based emergency demand response causes a statistically significant decline in electricity use with no additional financial burden on vulnerable groups. The electricity conservation potential of urban households was higher than that of rural households. Households with children did not respond to the emergency demand response, while the response of households with elderly individuals proved to be more positive. The repeated and frequent implementation of this policy did not result in an attenuation of the regulatory effect. This research can serve as a reference for countries with similar regulated power markets.
Cross-protection and cross-neutralization capacity of ancestral and VOC-matched SARS-CoV-2 adenoviral vector-based vaccines
Authors: Vinzón Sabrina E. , Lopez María V. , Cafferata Eduardo G. A. , Soto Ariadna S. , Berguer Paula M. , Vazquez Luciana , Nusblat Leonora , Pontoriero Andrea V. , Belotti Eduardo M. , Salvetti Natalia R. , Viale Diego L. , Vilardo Ariel E. , Avaro Martin M. , Benedetti Estefanía , Russo Mara L. , Dattero María E. , Carobene Mauricio , Sánchez-Lamas Maximiliano , Afonso Jimena , Heitrich Mauro , Cristófalo Alejandro E. , Otero Lisandro H. , Baumeister Elsa G. , Ortega Hugo H. , Edelstein Alexis , Podhajcer Osvaldo L.
Published: October 2023

COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge.
Universality in long-distance geometry and quantum complexity
Authors: Brown Adam R. , Freedman Michael H. , Lin Henry W. , Susskind Leonard
Published: October 2023

In physics, two systems that radically differ at short scales can exhibit strikingly similar macroscopic behaviour: they are part of the same long-distance universality class1. Here we apply this viewpoint to geometry and initiate a program of classifying homogeneous metrics on group manifolds2 by their long-distance properties. We show that many metrics on low-dimensional Lie groups have markedly different short-distance properties but nearly identical distance functions at long distances, and provide evidence that this phenomenon is even more robust in high dimensions. An application of these ideas of particular interest to physics and computer science is complexity geometry3–7—the study of quantum computational complexity using Riemannian geometry. We argue for the existence of a large universality class of definitions of quantum complexity, each linearly related to the other, a much finer-grained equivalence than typically considered. We conjecture that a new effective metric emerges at larger complexities that describes a broad class of complexity geometries, insensitive to various choices of microscopic penalty factors. We discuss the implications for recent conjectures in quantum gravity.
Scalable Infrastructure Supporting Reproducible Nationwide Healthcare Data Analysis toward FAIR Stewardship
Authors: Kim Ji-Woo , Kim Chungsoo , Kim Kyoung-Hoon , Lee Yujin , Yu Dong Han , Yun Jeongwon , Baek Hyeran , Park Rae Woong , You Seng Chan
Published: October 2023

Transparent and FAIR disclosure of meta-information about healthcare data and infrastructure is essential but has not been well publicized. In this paper, we provide a transparent disclosure of the process of standardizing a common data model and developing a national data infrastructure using national claims data. We established an Observational Medical Outcome Partnership (OMOP) common data model database for national claims data of the Health Insurance Review and Assessment Service of South Korea. To introduce a data openness policy, we built a distributed data analysis environment and released metadata based on the FAIR principle. A total of 10,098,730,241 claims and 56,579,726 patients’ data were converted as OMOP common data model. We also built an analytics environment for distributed research and made the metadata publicly available. Disclosure of this infrastructure to researchers will help to eliminate information inequality and contribute to the generation of high-quality medical evidence.
The R package for DICOM to brain imaging data structure conversion
Authors: Wulms Niklas , Eppe Sven , Dehghan-Nayyeri Mahboobeh , Streeter Adam J. , Bonberg Nadine , Berger Klaus , Sundermann Benedikt , Minnerup Heike
Published: October 2023

The BIDSconvertR package is the first R-based tool for organizing magnetic resonance imaging (MRI) research data in accordance with the Brain Imaging Data Structure (BIDS) specification. Key features are the DICOM (Digital Imaging and Communications in Medicine) to NIfTI (Neuroimaging Informatics Technology Initiative) and NIfTI to BIDS conversion, the implementation of the BIDS Validator and a MRI data viewer to efficiently manage MRI neuroimaging data sets. The BIDSconvertR offers an interactive user dialogue and a graphical user interface. BIDS validation is facilitated by color-coding of the BIDS sequence-IDs. Data cleaning is simplified by the option of using regular expressions. The BIDSconvertR contributes to the growing efforts to improve reproducibility in neuroimaging research by facilitating researchers to share and organize data in a standardized and transparent manner.
Chromosome-level genome assembly of an important wolfberry fruit fly (Neoceratitis asiatica Becker)
Authors: Guo Shaokun , Liu Bo , He Jia , Zhao Zihua , Zhang Rong , Li Zhihong
Published: October 2023

Tephritidae pests are significant agricultural pests with a notable impact on the economy, with a wide range of species and most having broad host ranges and strong reproductive abilities. However, the wolfberry fruit fly, Neoceratitis asiatica (Becker), is a Tephritidae fly which only harms wolfberry. Here, we assembled and annotated N. asiatica genome at the chromosome level and compared it with the genomic and transcriptomic information from other Tephritidae flies. The assembled genome of N. asiatica had a size of 563.8 Mb and achieved a completeness level of 99.1%, 18,387 genes were annotated totally. All contigs were assembled into 7 linkage groups with an N50 of 93.166 Mb assisted by the Hi-C technique. The high-quality genome developed here will provide a significant resource for exploring the genetic basis of the adaptive and reproductive differences among various Tephritidae pests, and provides an important theoretical basis for the prevention and control of Tephritidae pests.
Major histocompatibility complex complement (MHC) Bf alleles show trans species evolution between man and chimpanzee
Authors: Arnaiz-Villena Antonio , Juarez Ignacio , Sánchez-Orta Alejandro , Martín-Villa José Manuel , Suarez-Trujillo Fabio
Published: October 2023

HLA and disease studies by using single allele statistics have been fruitless during the last 40 years for explaining association pathogenesis of the associated diseases.Other approaches are necessary to untangle this puzzle. We aim to revisit complement alleleism in humans and primates for both studying MHC and disease association to complotypes and extended MHC haplotypes in order to also explain the positive directional selection of maintaining immune response genes (complement, MHC adaptive and MHC non-specific genes) that keeps these three type of genes together in a short chromosome stretch (MHC) for million years. These genes may be linked to conjointly avoid microbes attack and autoimmunity. In the present paper, it is obtained a new Bf chimpanzee allele, provisionaly named Patr-Bf*A:01,that differs from other Bf alleles by having CTG at eleventh codon of exon 2 in order to start the newly suggested methodology and explain functional and evolutionary MHC obscure aspects. Exons 1 to 6 of Ba fragment of Bf gene were obtained from chimpanzee. This new chimpanzee Factor B allele (Patr-Bf*A:01) is to be identical to a infrequent human Bf allele (SNP rs641153); it stresses the strong evolutive pressure upon certain alleles that are trans specific. It also may apply to MHC extended haplotipes which may conjointly act to start an adequate immune response. It is the first time that a complement MHC class III allele is described to undergo trans species evolution,in contrast to class I and class II alleles which had already been reported . Allelism of complement factors are again proposed for studying MHC complement genes, complotypes, and extended MHC haplotypes which may be more informative that single MHC marker studies.
Disease pathology signatures in a mouse model of Mucopolysaccharidosis type IIIB
Authors: Petrova Ralitsa , Patil Abhijeet R. , Trinh Vivian , McElroy Kathryn E. , Bhakta Minoti , Tien Jason , Wilson David S. , Warren Liling , Stratton Jennifer R.
Published: October 2023

Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare and devastating childhood-onset lysosomal storage disease caused by complete loss of function of the lysosomal hydrolase α-N-acetylglucosaminidase. The lack of functional enzyme in MPS IIIB patients leads to the progressive accumulation of heparan sulfate throughout the body and triggers a cascade of neuroinflammatory and other biochemical processes ultimately resulting in severe mental impairment and early death in adolescence or young adulthood. The low prevalence and severity of the disease has necessitated the use of animal models to improve our knowledge of the pathophysiology and for the development of therapeutic treatments. In this study, we took a systematic approach to characterizing a classical mouse model of MPS IIIB. Using a series of histological, biochemical, proteomic and behavioral assays, we tested MPS IIIB mice at two stages: during the pre-symptomatic and early symptomatic phases of disease development, in order to validate previously described phenotypes, explore new mechanisms of disease pathology and uncover biomarkers for MPS IIIB. Along with previous findings, this study helps provide a deeper understanding of the pathology landscape of this rare disease with high unmet medical need and serves as an important resource to the scientific community.
Wild harbour porpoises startle and flee at low received levels from acoustic harassment device
Authors: Elmegaard Siri L. , Teilmann Jonas , Rojano-Doñate Laia , Brennecke Dennis , Mikkelsen Lonnie , Balle Jeppe D. , Gosewinkel Ulrich , Kyhn Line A. , Tønnesen Pernille , Wahlberg Magnus , Ruser Andreas , Siebert Ursula , Madsen Peter Teglberg
Published: October 2023

Acoustic Harassment Devices (AHD) are widely used to deter marine mammals from aquaculture depredation, and from pile driving operations that may otherwise cause hearing damage. However, little is known about the behavioural and physiological effects of these devices. Here, we investigate the physiological and behavioural responses of harbour porpoises (Phocoena phocoena) to a commercial AHD in Danish waters. Six porpoises were tagged with suction-cup-attached DTAGs recording sound, 3D-movement, and GPS (n = 3) or electrocardiogram (n = 2). They were then exposed to AHDs for 15 min, with initial received levels (RL) ranging from 98 to 132 dB re 1 µPa (rms-fast, 125 ms) and initial exposure ranges of 0.9–7 km. All animals reacted by displaying a mixture of acoustic startle responses, fleeing, altered echolocation behaviour, and by demonstrating unusual tachycardia while diving. Moreover, during the 15-min exposures, half of the animals received cumulative sound doses close to published thresholds for temporary auditory threshold shifts. We conclude that AHD exposure at many km can evoke both startle, flight and cardiac responses which may impact blood-gas management, breath-hold capability, energy balance, stress level and risk of by-catch. We posit that current AHDs are too powerful for mitigation use to prevent hearing damage of porpoises from offshore construction.
An environmental justice analysis of air pollution in India
Authors: deSouza Priyanka N. , Chaudhary Ekta , Dey Sagnik , Ko Soohyeon , Németh Jeremy , Guttikunda Sarath , Chowdhury Sourangsu , Kinney Patrick , Subramanian S. V. , Bell Michelle L. , Kim Rockli
Published: October 2023

Due to the lack of timely data on socioeconomic factors (SES), little research has evaluated if socially disadvantaged populations are disproportionately exposed to higher PM2.5 concentrations in India. We fill this gap by creating a rich dataset of SES parameters for 28,081 clusters (villages in rural India and census-blocks in urban India) from the National Family and Health Survey (NFHS-4) using a precision-weighted methodology that accounts for survey-design. We then evaluated associations between total, anthropogenic and source-specific PM2.5 exposures and SES variables using fully-adjusted multilevel models. We observed that SES factors such as caste, religion, poverty, education, and access to various household amenities are important risk factors for PM2.5 exposures. For example, we noted that a unit standard deviation increase in the cluster-prevalence of Scheduled Caste and Other Backward Class households was significantly associated with an increase in total-PM2.5 levels corresponding to 0.127 μg/m3 (95% CI 0.062 μg/m3, 0.192 μg/m3) and 0.199 μg/m3 (95% CI 0.116 μg/m3, 0.283 μg/m3, respectively. We noted substantial differences when evaluating such associations in urban/rural locations, and when considering source-specific PM2.5 exposures, pointing to the need for the conceptualization of a nuanced EJ framework for India that can account for these empirical differences. We also evaluated emerging axes of inequality in India, by reporting associations between recent changes in PM2.5 levels and different SES parameters.
Lactobacillus paracasei HII01 enhances lifespan and promotes neuroprotection in Caenorhabditis elegans
Authors: Kumaree Kishoree K. , Prasanth Mani Iyer , Sivamaruthi Bhagavathi Sundaram , Kesika Periyanaina , Tencomnao Tewin , Chaiyasut Chaiyavat , Prasansuklab Anchalee
Published: October 2023

Achieving healthy aging and providing protection from aging-related diseases is a major global concern. Probiotics, are a safer and more natural alternative. Moreover, identifying novel probiotics can help develop a new therapeutic approach and may help in personalized probiotic-formulations for individual's unique gut microbiome. In this study, we evaluated the benefits of our novel probiotic strains in promoting healthy aging and whether they protect against Amyloid β toxicity of Alzheimer's disease. Henceforth, we analyzed the impact of four different probiotics (Lactobacillus paracasei HII01, L. rhamnosus, L. reuteri, L. salivarius) on the lifespan extension of Caenorhabditis elegans model. Our results determine that L. paracasei HII01 provided the most positive effect on longevity and antiaging effects on C. elegans. The qPCR data and mutant-based studies indicated that L. paracasei HII01-mediated lifespan extension could be modulated by DAF-16 mediated pathway. The probiotic strains also protected the worms from the toxicity induced by β-Amyloid-expressing (Aβ) transgenic C. elegans strains, and L. paracasei HII01 provided the most significant protection. Overall, identifying novel probiotics is an important area of research that can improve health outcomes. Our study showed that L. paracasei HII01 could be considered a dietary supplement for providing healthy aging and preventing aging-related diseases.