bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking environmental injustices in Detroit, MI to institutional racial segregation through historical federal redlining
Authors: Shkembi Abas , Smith Lauren M. , Neitzel Richard L. 
Published: December 2022

Abstract
Objectives
To identify the most pervasive environmental exposures driving environmental disparities today associated with historical redlining in Detroit.

Methods
We overlaid Detroit’s 1939 Home Owners’ Loan Corporation (HOLC) shapefile from the Mapping Inequality project onto the EPA EJScreen and the DOT National Transportation Noise maps to analyze differences in current demographic and environmental indicators between historically redlined (D-grade) and non-redlined neighborhoods using simple linear regression and a boosted classification tree algorithm.

Results
Historically redlined neighborhoods in Detroit experienced significantly higher environmental hazards than non-redlined neighborhoods in the form of 12.1% (95% CI: 7.2–17.1%) higher levels of diesel particulate matter (PM), 32.2% (95% CI: 3.3–69.3%) larger traffic volumes, and 65.7% (95% CI: 8.6–152.8%) higher exposure to hazardous road noise (LEQ(24h) >70 dBA). Historically redlined neighborhoods were situated near 1.7-times (95% CI: 1.4–2.1) more hazardous waste sites and twice as many (95% CI: 1.5–2.7) risk management plan (RMP) sites than non-redlined neighborhoods. The lifetime cancer risk from inhalation of air toxics was 4.4% (95% CI: 2.9–6.6%) higher in historically redlined communities, and the risk of adverse respiratory health outcomes from air toxics was 3.9% (95% CI: 2.1–5.6%) higher. All factors considered together, among the environmental hazards considered, the most pervasive hazards in historically redlined communities are proximity to RMP sites, hazardous road noise, diesel PM, and cancer risk from air pollution.

Conclusions
Historically redlined neighborhoods may have a disproportionately higher risk of developing cancer and adverse respiratory health outcomes from air toxics. Policies targeting air and noise pollution from transportation sources, particularly from sources of diesel exhaust, in historically redlined neighborhoods may ameliorate some of the impacts of structural environmental racism from historical redlining in Detroit.
Functional investigation of SLC1A2 variants associated with epilepsy
Authors: Qu Qi , Zhang Wenlong , Wang Ji , Mai Dongmei , Ren Siqiang , Qu Shaogang , Zhang Yunlong 
Published: December 2022

AbstractEpilepsy is a common neurological disorder and glutamate excitotoxicity plays a key role in epileptic pathogenesis. Astrocytic glutamate transporter GLT-1 is responsible for preventing excitotoxicity via clearing extracellular accumulated glutamate. Previously, three variants (G82R, L85P, and P289R) in SLC1A2 (encoding GLT-1) have been clinically reported to be associated with epilepsy. However, the functional validation and underlying mechanism of these GLT-1 variants in epilepsy remain undetermined. In this study, we reported that these disease-linked mutants significantly decrease glutamate uptake, cell membrane expression of the glutamate transporter, and glutamate-elicited current. Additionally, we found that these variants may disturbed stromal-interacting molecule 1 (STIM1)/Orai1-mediated store-operated Ca2+ entry (SOCE) machinery in the endoplasmic reticulum (ER), in which GLT-1 may be a new partner of SOCE. Furthermore, knock-in mice with disease-associated variants showed a hyperactive phenotype accompanied by reduced glutamate transporter expression. Therefore, GLT-1 is a promising and reliable therapeutic target for epilepsy interventions.
Tumor immune microenvironment and immunotherapy efficacy in BRAF mutation non-small-cell lung cancer
Authors: Li Hui , Zhang Yongchang , Xu Yanjun , Huang Zhiyu , Cheng Guoping , Xie Mingyin , Zhou Zichao , Yu Yangyang , Xi Wenjing , Fan Yun 
Published: December 2022

AbstractPrevious small-size studies reported BRAF-mutated NSCLC patients have comparable sensitivity to immune checkpoint inhibitors (ICIs). However, how BRAF mutation affects the tumor immune microenvironment (TIME) is unknown. We performed Nanostring-panel RNA sequencing to evaluate TIME in 57 BRAF mutated and wild-type (WT) NSCLC specimens (cohort A). The efficacy of ICI monotherapy or combined therapies was determined in 417 patients with WT and BRAF mutated NSCLC (cohort B). We found that BRAF-mutant tumors had similar ratios of CD8+ T cells to Tregs, the balance of cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar TIME pattern was observed between the BRAF V600E and Non-V600E subgroups of NSCLC. The further retrospective study confirmed that treatment with ICI monotherapy or combined therapies resulted in similar overall survival (OS) (HR: 0.85; 95% CI, 0.56 to 1.30; p = 0.47) and progress-free survival (PFS) (HR: 1.02; 95% CI, 0.72 to 1.44; p = 0.91) of patients with WT (n = 358) and BRAF mutant (n = 59) NSCLC. Similarly, both patients with BRAF V600E or Non-V600E NSCLC had similar responses to immunotherapy. Our findings support that BRAF mutation did not modulate TIME in NSCLC and therapeutic responses to ICIs. Patients with NSCLC harboring BRAF mutation should not be denied treatment with ICIs.
SARS-CoV-2 vaccination-infection pattern imprints and diversifies T cell differentiation and neutralizing response against Omicron subvariants
Authors: Wang Junxiang , Li Kaiyi , Mei Xinyue , Cao Jinpeng , Zhong Jiaying , Huang Peiyu , Luo Qi , Li Guichang , Wei Rui , Zhong Nanshan , Zhao Zhuxiang , Wang Zhongfang 
Published: December 2022

AbstractThe effects of different SARS-CoV-2 vaccinations and variant infection histories on imprinting population immunity and their influence on emerging escape mutants remain unclear. We found that Omicron (BA.1) breakthrough infection, regardless of vaccination with two-dose mRNA vaccines (M-M-o) or two-dose inactivated vaccines (I-I-o), led to higher neutralizing antibody levels against different variants and stronger T-cell responses than Delta breakthrough infection after two-dose inactivated vaccine vaccination (I-I-δ). Furthermore, different vaccination-infection patterns imprinted virus-specific T-cell differentiation; M-M-ο showed higher S/M/N/E-specific CD4+ T cells and less portion of virus-specific CD45RA+CD27–CD8+ T cells by ex vivo assay. Breakthrough infection groups showed higher proliferation and multi-function capacity by in vitro assay than three-dose inactivated vaccine inoculated group (I-I-I). Thus, under wide vaccination coverage, the higher immunogenicity with the Omicron variant may have helped to eliminate the population of Delta variant. Overall, our data contribute to our understanding of immune imprinting in different sub-populations and may guide future vaccination programs.
Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling
Authors: Fernandez Lahore Rodrigo G. , Pampaloni Niccolò P. , Schiewer Enrico , Heim M.-Marcel , Tillert Linda , Vierock Johannes , Oppermann Johannes , Walther Jakob , Schmitz Dietmar , Owald David , Plested Andrew J. R. , Rost Benjamin R. , Hegemann Peter 
Published: December 2022

AbstractChannelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H+, Na+, K+ and anions have been discovered or engineered, Ca2+-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca2+ permeability and improve their Ca2+ affinity by targeted mutagenesis at the central selectivity filter. The engineered channels, termed CapChR1 and CapChR2 for calcium-permeable channelrhodopsins, exhibit reduced sodium and proton conductance in connection with strongly improved Ca2+ permeation at negative voltage and low extracellular Ca2+ concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca2+ concentrations. Moreover, CapChR2 can robustly trigger Ca2+ signalling in hippocampal neurons. When expressed together with genetically encoded Ca2+ indicators in Drosophila melanogaster mushroom body output neurons, CapChRs mediate light-evoked Ca2+ entry in brain explants.
Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation
Authors: Lim Ryan G. , Al-Dalahmah Osama , Wu Jie , Gold Maxwell P. , Reidling Jack C. , Tang Guomei , Adam Miriam , Dansu David K. , Park Hye-Jin , Casaccia Patrizia , Miramontes Ricardo , Reyes-Ortiz Andrea M. , Lau Alice , Hickman Richard A. , Khan Fatima , Paryani Fahad , Tang Alice , Ofori Kenneth , Miyoshi Emily , Michael Neethu , McClure Nicolette , Flowers Xena E. , Vonsattel Jean Paul , Davidson Shawn , Menon Vilas , Swarup Vivek , Fraenkel Ernest , Goldman James E. , Thompson Leslie M. 
Published: December 2022

AbstractThe complexity of affected brain regions and cell types is a challenge for Huntington’s disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulatorsOLIG1andOLIG2are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identifyPRKCEand Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate forTPK1dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.
Single-shot 3D imaging with point cloud projection based on metadevice
Authors: Jing Xiaoli , Zhao Ruizhe , Li Xin , Jiang Qiang , Li Chengzhi , Geng Guangzhou , Li Junjie , Wang Yongtian , Huang Lingling 
Published: December 2022

AbstractThree-dimensional (3D) imaging is a crucial information acquisition technology for light detection, autonomous vehicles, gesture recognition, machine vision, and other applications. Metasurface, as a subwavelength scale two-dimensional array, offers flexible control of optical wavefront owing to abundant design freedom. Metasurfaces are promising for use as optical devices because they have large field of view and powerful functionality. In this study, we propose a flat optical device based on a single-layer metasurface to project a coded point cloud in the Fourier space and explore a sophisticated matching algorithm to achieve 3D reconstruction, offering a complete technical roadmap for single-shot detection. We experimentally demonstrate that the depth accuracy of our system is smaller than 0.24 mm at a measurement distance of 300 mm, indicating the feasibility of the submillimetre measurement platform. Our method can pave the way for practical applications such as surface shape detection, gesture recognition, and personal authentication.
The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3
Authors: Ishimura Ryosuke , El-Gowily Afnan H. , Noshiro Daisuke , Komatsu-Hirota Satoko , Ono Yasuko , Shindo Mayumi , Hatta Tomohisa , Abe Manabu , Uemura Takefumi , Lee-Okada Hyeon-Cheol , Mohamed Tarek M. , Yokomizo Takehiko , Ueno Takashi , Sakimura Kenji , Natsume Tohru , Sorimachi Hiroyuki , Inada Toshifumi , Waguri Satoshi , Noda Nobuo N. , Komatsu Masaaki 
Published: December 2022

AbstractProtein modification by ubiquitin-like proteins (UBLs) amplifies limited genome information and regulates diverse cellular processes, including translation, autophagy and antiviral pathways. Ubiquitin-fold modifier 1 (UFM1) is a UBL covalently conjugated with intracellular proteins through ufmylation, a reaction analogous to ubiquitylation. Ufmylation is involved in processes such as endoplasmic reticulum (ER)-associated protein degradation, ribosome-associated protein quality control at the ER and ER-phagy. However, it remains unclear how ufmylation regulates such distinct ER-related functions. Here we identify a UFM1 substrate, NADH-cytochrome b5 reductase 3 (CYB5R3), that localizes on the ER membrane. Ufmylation of CYB5R3 depends on the E3 components UFL1 and UFBP1 on the ER, and converts CYB5R3 into its inactive form. Ufmylated CYB5R3 is recognized by UFBP1 through the UFM1-interacting motif, which plays an important role in the further uyfmylation of CYB5R3. Ufmylated CYB5R3 is degraded in lysosomes, which depends on the autophagy-related protein Atg7- and the autophagy-adaptor protein CDK5RAP3. Mutations ofCYB5R3and genes involved in the UFM1 system cause hereditary developmental disorders, and ufmylation-defectiveCyb5r3knock-in mice exhibit microcephaly. Our results indicate that CYB5R3 ufmylation induces ER-phagy, which is indispensable for brain development.
Molecular mechanism of antibody neutralization of coxsackievirus A16
Authors: Zhang Chao , Liu Caixuan , Shi Jinping , Wang Yalei , Xu Cong , Ye Xiaohua , Liu Qingwei , Li Xue , Qiao Weihua , Yin Yannan , Cong Yao , Huang Zhong 
Published: December 2022

AbstractCoxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.
Inheritance of paternal DNA damage by histone-mediated repair restriction
Authors: Wang Siyao , Meyer David H. , Schumacher Björn 
Published: December 2022

AbstractHow paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question in radiation biology. In humans, nearly 80% of transmitted mutations arise in the paternal germline1, but the transgenerational effects of ionizing radiation exposure has remained controversial and the mechanisms are unknown. Here we show that in sex-separated Caenorhabditis elegans strains, paternal, but not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males displayed various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement and aneuploidy. Paternal DNA double strand breaks were repaired by maternally provided error-prone polymerase theta-mediated end joining. Mechanistically, we show that depletion of an orthologue of human histone H1.0, HIS-24, or the heterochromatin protein HPL-1, could significantly reverse the transgenerational embryonic lethality. Removal of HIS-24 or HPL-1 reduced histone 3 lysine 9 dimethylation and enabled error-free homologous recombination repair in the germline of the F1 generation from ionizing radiation-treated P0 males, consequently improving the viability of the F2 generation. This work establishes the mechanistic underpinnings of the heritable consequences of paternal radiation exposure on the health of offspring, which may lead to congenital disorders and cancer in humans.
A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk
Authors: Rottner Antje K. , Ye Yingying , Navarro-Guerrero Elena , Rajesh Varsha , Pollner Alina , Bevacqua Romina J. , Yang Jing , Spigelman Aliya F. , Baronio Roberta , Bautista Austin , Thomsen Soren K. , Lyon James , Nawaz Sameena , Smith Nancy , Wesolowska-Andersen Agata , Fox Jocelyn E. Manning , Sun Han , Kim Seung K. , Ebner Daniel , MacDonald Patrick E. , Gloyn Anna L. 
Published: December 2022

AbstractIdentification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many of the genetic signals for type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in a human pancreatic beta cell line. We assessed the regulation of insulin content as a disease-relevant readout of beta cell function and identified 580 genes influencing this phenotype. Integration with genetic and genomic data provided experimental support for 20 candidate T2D effector transcripts including the autophagy receptorCALCOCO2. Loss ofCALCOCO2was associated with distorted mitochondria, less proinsulin-containing immature granules and accumulation of autophagosomes upon inhibition of late-stage autophagy. Carriers of T2D-associated variants at theCALCOCO2locus further displayed altered insulin secretion. Our study highlights how cellular screens can augment existing multi-omic efforts to support mechanistic understanding and provide evidence for causal effects at genome-wide association studies loci.
Empirical evaluation of computational models of lightness perception
Authors: Nedimović Predrag , Zdravković Sunčica , Domijan Dražen 
Published: December 2022

AbstractLightness of a surface depends not only on its physical characteristics, but also on the properties of the surrounding context. As a result, varying the context can significantly alter surface lightness, an effect exploited in many lightness illusions. Computational models can produce outcomes similar to human illusory percepts, allowing for demonstrable assessment of the applied mechanisms and principles. We tested 8 computational models on 13 typical displays used in lightness research (11 Illusions and 2 Mondrians), and compared them with results from human participants (N = 85). Results show that HighPass and MIR models predict empirical results for simultaneous lightness contrast (SLC) and its close variations. ODOG and its newer variants (ODOG-2 and L-ODOG) in addition to SLC displays were able to predict effect of White’s illusion. RETINEX was able to predict effects of both SLC displays and Dungeon illusion. Dynamic decorrelation model was able to predict obtained effects for all tested stimuli except two SLC variations. Finally, FL-ODOG model was best at simulating human data, as it was able to predict empirical results for all displays, bar the Reversed contrast illusion. Finally, most models underperform on the Mondrian displays that represent most natural stimuli for the human visual system.
Ketamine induces apical extracellular matrix modifications in Caenorhabditis elegans
Authors: Yücel Duygu 
Published: December 2022

AbstractKetamine is a widely used anesthetic agent since 1960s and has recently been exploited for its rapid antidepressant action at subanesthetic doses. It has been demonstrated that ketamine induces alterations in extracellular matrix (ECM) in rodent models which in part plays a role in its anti-depressant action. The nematodeCaenorhabditis elegansserves as a powerful tool for understanding mechanisms of drug action with its short life cycle, genetic amenability and conserved cellular processes. Further investigation is required particularly in in vivo systems to gain broader understanding of ketamine’s actions. In this study, we aimed to decipher ketamine-mediated alterations usingC. elegansas a model. We show that ketamine specifically induces apical extracellular matrix modifications (aECM) in the vulva and the cuticle. Ketamine treatment phenocopies neuronal migration and vulval invagination defects of chondroitin mutants despite wild-type like chondroitin staining pattern. Normal vulval expansion and defective vulval eversion phenotypes of ketamine-treated animals are suggestive of alterations in the network of aECM factors which do not impinge on chondroitin. Ketamine ameliorates impaired movement of a group ofrollermutants characterised with collagen defects in the cuticle and RNA-seq identifies that 30% of the cuticular collagens are upregulated in response to ketamine. Ketamine alters aECM, neuronal migration and collagen expression inC. elegans. We proposeC. elegansas a putative animal model to investigate ketamine-mediated ECM modifications.
Production enhancement of human adipose-derived mesenchymal stem cells by low-intensity ultrasound stimulation
Authors: Min Soohong , Byeon Yungsun , Kim Min , Lee Youngjun , Lee Sung-Hoon , Lee Youngjun , Farooqi Hafiz Muhammad Umer , Lee Hong-Ki , Paeng Dong-Guk 
Published: December 2022

AbstractLow-intensity ultrasound (LIUS) enhances the proliferation rate of various mammalian stem cells through mechanical stimulation. This study quantitively finds suitable LIUS stimulation parameters for increasing the proliferation rate of human adipose-derived mesenchymal stem cells (hAdMSCs) for mass production. Various stimulation conditions of LIUS were assessed based on the beam pattern of the ultrasonic transducer and the attenuation of the sound waves. Using optimal LIUS stimulation parameters for enhancing proliferation of hAdMSCs taken from bromodeoxyuridine (BrdU) incorporation assay, long-term culture of hAdMSCs was performed for 16 days. The resultant hAdMSCs were characterized for various biomarkers such as CD34−, CD45−, CD73+, CD95+, CD105+ and cytological staining and a cytokine array assay. LIUS stimulation parameters found for enhancing the hAdMSCs proliferation were the frequency of 5 MHz, an intensity of 300 mWcm−2, a duration of 10 min per day, and continuous waves with a 100% duty cycle. The LIUS stimulated hAdMSCs group showed a 3.25-fold increase in the cell number compared to the control group after 16 days of culture. By confirming the effects of quantitatively measured LIUS stimulation on the enhancement of hAdMSCs proliferation, this study may be a foundation for the applications of LIUS stimulation in the industrial-scale production of hAdMSCs.