bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Authors: Hu Ming-Ming , Shu Hong-Bing 
Published: November 2023

AbstractVarious cellular stress conditions trigger mitochondrial DNA (mtDNA) release from mitochondria into the cytosol. The released mtDNA is sensed by the cGAS-MITA/STING pathway, resulting in the induced expression of type I interferon and other effector genes. These processes contribute to the innate immune response to viral infection and other stress factors. The deregulation of these processes causes autoimmune diseases, inflammatory metabolic disorders and cancer. Therefore, the cGAS-MITA/STING pathway is a potential target for intervention in infectious, inflammatory and autoimmune diseases as well as cancer. In this review, we focus on the mechanisms underlying the mtDNA-triggered activation of the cGAS-MITA/STING pathway, the effects of the pathway under various physiological and pathological conditions, and advances in the development of drugs that target cGAS and MITA/STING.
Rapid disintegration and weakening of ice shelves in North Greenland
Authors: Millan R. , Jager E. , Mouginot J. , Wood M. H. , Larsen S. H. , Mathiot P. , Jourdain N. C. , Bjørk A. 
Published: November 2023

AbstractThe glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.
An artificially-intelligent cornea with tactile sensation enables sensory expansion and interaction
Authors: Qu Shangda , Sun Lin , Zhang Song , Liu Jiaqi , Li Yue , Liu Junchi , Xu Wentao 
Published: November 2023

AbstractWe demonstrate an artificially-intelligent cornea that can assume the functions of the native human cornea such as protection, tactile perception, and light refraction, and possesses sensory expansion and interactive functions. These functions are realized by an artificial corneal reflex arc that is constructed to implement mechanical and light information coding, information processing, and the regulation of transmitted light. Digitally-aligned, long and continuous zinc tin oxide (ZTO) semiconductor fabric patterns were fabricated as the active channels of the artificial synapse, which are non-toxic, heavy-metal-free, low-cost, and ensure superior comprehensive optical properties (transmittance >99.89%, haze <0.36%). Precisely-tuned crystal-phase structures of the ZTO fibers enabled reconfigurable synaptic plasticity, which is applicable to encrypted communication and associative learning. This work suggests new strategies for the tuning of synaptic plasticity and the design of visual neuroprosthetics, and has important implications for the development of neuromorphic electronics and for visual restoration.
Direct detection of atomic oxygen on the dayside and nightside of Venus
Authors: Hübers Heinz-Wilhelm , Richter Heiko , Graf Urs U. , Güsten Rolf , Klein Bernd , Stutzki Jürgen , Wiesemeyer Helmut 
Published: November 2023

AbstractAtomic oxygen is a key species in the mesosphere and thermosphere of Venus. It peaks in the transition region between the two dominant atmospheric circulation patterns, the retrograde super-rotating zonal flow below 70 km and the subsolar to antisolar flow above 120 km altitude. However, past and current detection methods are indirect and based on measurements of other molecules in combination with photochemical models. Here, we show direct detection of atomic oxygen on the dayside as well as on the nightside of Venus by measuring its ground-state transition at 4.74 THz (63.2 µm). The atomic oxygen is concentrated at altitudes around 100 km with a maximum column density on the dayside where it is generated by photolysis of carbon dioxide and carbon monoxide. This method enables detailed investigations of the Venusian atmosphere in the region between the two atmospheric circulation patterns in support of future space missions to Venus.
Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies
Authors: Gouveia Mateus H. , Bentley Amy R. , Leal Thiago P. , Tarazona-Santos Eduardo , Bustamante Carlos D. , Adeyemo Adebowale A. , Rotimi Charles N. , Shriner Daniel 
Published: November 2023

AbstractEuropean-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrate individual-level genome-wide data from ~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generate a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European Americans are admixed at the subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant in LCT (rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association between LCT and body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
Vegetation controls on channel network complexity in coastal wetlands
Authors: van de Vijsel Roeland C. , van Belzen Jim , Bouma Tjeerd J. , van der Wal Daphne , Borsje Bas W. , Temmerman Stijn , Cornacchia Loreta , Gourgue Olivier , van de Koppel Johan 
Published: November 2023

AbstractChannel networks are key to coastal wetland functioning and resilience under climate change. Vegetation affects sediment and hydrodynamics in many different ways, which calls for a coherent framework to explain how vegetation shapes channel network geometry and functioning. Here, we introduce an idealized model that shows how coastal wetland vegetation creates more complexly branching networks by increasing the ratio of channel incision versus topographic diffusion rates, thereby amplifying the channelization feedback that recursively incises finer-scale side-channels. This complexification trend qualitatively agrees with and provides an explanation for field data presented here as well as in earlier studies. Moreover, our model demonstrates that a stronger biogeomorphic feedback leads to higher and more densely vegetated marsh platforms and more extensive drainage networks. These findings may inspire future field research by raising the hypothesis that vegetation-induced self-organization enhances the storm surge buffering capacity of coastal wetlands and their resilience under sea-level rise.
Forgotten memory storage and retrieval in Drosophila
Authors: Wang Chih-Ming , Wu Chun-Yuan , Lin Chen-En , Hsu Ming-Chi , Lin Jing-Chun , Huang Chuan-Chin , Lien Ting-Yu , Lin Hsin-Kai , Chang Ting-Wei , Chiang Hsueh-Cheng 
Published: November 2023

AbstractInaccessibility of stored memory in ensemble cells through the forgetting process causes animals to be unable to respond to natural recalling cues. While accumulating evidence has demonstrated that reactivating memory-stored cells can switch cells from an inaccessible state to an accessible form and lead to recall of previously learned information, the underlying cellular and molecular mechanisms remain elusive. The current study used Drosophila as a model to demonstrate that the memory of one-trial aversive olfactory conditioning, although inaccessible within a few hours after learning, is stored in KCαβ and retrievable after mild retraining. One-trial aversive conditioning triggers protein synthesis to form a long-lasting cellular memory trace, approximately 20 days, via creb in KCαβ, and a transient cellular memory trace, approximately one day, via orb in MBON-α3. PPL1-α3 negatively regulates forgotten one-trial conditioning memory retrieval. The current study demonstrated that KCαβ, PPL1-α3, and MBON-α3 collaboratively regulate the formation of forgotten one-cycle aversive conditioning memory formation and retrieval.
Candidate genes under selection in song sparrows co-vary with climate and body mass in support of Bergmann’s Rule
Authors: Carbeck Katherine , Arcese Peter , Lovette Irby , Pruett Christin , Winker Kevin , Walsh Jennifer 
Published: November 2023

AbstractEcogeographic rules denote spatial patterns in phenotype and environment that may reflect local adaptation as well as a species’ capacity to adapt to change. To identify genes underlying Bergmann’s Rule, which posits that spatial correlations of body mass and temperature reflect natural selection and local adaptation in endotherms, we compare 79 genomes from nine song sparrow (Melospiza melodia) subspecies that vary ~300% in body mass (17 − 50 g). Comparing large- and smaller-bodied subspecies revealed 9 candidate genes in three genomic regions associated with body mass. Further comparisons to the five smallest subspecies endemic to California revealed eight SNPs within four of the candidate genes (GARNL3, RALGPS1, ANGPTL2, and COL15A1) associated with body mass and varying as predicted by Bergmann’s Rule. Our results support the hypothesis that co-variation in environment, body mass and genotype reflect the influence of natural selection on local adaptation and a capacity for contemporary evolution in this diverse species.
Structural basis of peptide secretion for Quorum sensing by ComA
Authors: Yu Lin , Xu Xin , Chua Wan-Zhen , Feng Hao , Ser Zheng , Shao Kai , Shi Jian , Wang Yumei , Li Zongli , Sobota Radoslaw M. , Sham Lok-To , Luo Min 
Published: November 2023

AbstractQuorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as Streptococcus pneumoniae, ComA is a conserved efflux pump responsible for the maturation and secretion of peptide signals, including the competence-stimulating peptide (CSP), yet its structure and function remain unclear. Here, we functionally characterize ComA as an ABC transporter with high ATP affinity and determined its cryo-EM structures in the presence or absence of CSP or nucleotides. Our findings reveal a network of strong electrostatic interactions unique to ComA at the intracellular gate, a putative binding pocket for two CSP molecules, and negatively charged residues facilitating CSP translocation. Mutations of these residues affect ComA’s peptidase activity in-vitro and prevent CSP export in-vivo. We demonstrate that ATP-Mg2+ triggers the outward-facing conformation of ComA for CSP release, rather than ATP alone. Our study provides molecular insights into the QS signal peptide secretion, highlighting potential targets for QS-targeting drugs.
Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration
Authors: Liu Chi , Liu Xiaoliang , He Zhongwei , Zhang Jiangping , Tan Xiaoqin , Yang Wenmin , Zhang Yunfeng , Yu Ting , Liao Shuyi , Dai Lu , Xu Zhi , Li Furong , Huang Yinghui , Zhao Jinghong 
Published: November 2023

AbstractOrgan regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.
RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing
Authors: Moursy Ahmed , Cléry Antoine , Gerhardy Stefan , Betz Katharina M. , Rao Sanjana , Mazur Jarosław , Campagne Sébastien , Beusch Irene , Duszczyk Malgorzata M. , Robinson Mark D. , Panse Vikram Govind , Allain Frédéric H.-T. 
Published: November 2023

AbstractThe conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.
C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule
Authors: Zeng Yue , Shi Wei , Liu Zhi , Xu Hao , Liu Liya , Hang Jiaying , Wang Yongqin , Lu Mengru , Zhou Wei , Huang Wei , Tang Feng 
Published: November 2023

AbstractThe precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.
Efficient PFOA removal from drinking water by a dual-functional mixed-matrix-composite nanofiltration membrane
Authors: Chaudhary Mohit , Sela-Adler Michal , Ronen Avner , Nir Oded 
Published: November 2023

AbstractDrinking water contamination by per- and polyfluorinated alkyl substances (PFAS) is a global concern. Nanofiltration is a promising PFAS removal technology due to its scalability and cost-effectiveness. However, nanofiltration cannot typically reduce PFAS concentrations below current drinking water recommendations. To enhance PFAS removal, we developed mixed-matrix-composite nanofiltration (MMCNF) membranes—an active nanofiltration layer on porous adsorptive support that synergetically combines filtration and adsorption. We synthesized MMCNF membranes comprising thin polyelectrolyte multilayer films deposited on thick (~400 µm) polyethersulfone supports incorporating β-cyclodextrin microparticles. These membranes achieved near complete removal (>99.9%) of model PFAS (PFOA: perfluorooctanoic acid) for significantly longer filtration times compared to a control membrane without β-cyclodextrin, but otherwise identical. The spent MMCNF membrane was regenerated using ethanol, and high PFOA removal performance was regained during three filtration cycles. Perfluorooctanoic acid was concentrated 38-fold in the ethanol eluent. Further concentration by evaporation is straightforward and can enable eluent recycling and effective PFAS removal.
Early Eocene low orography and high methane enhance Arctic warming via polar stratospheric clouds
Authors: Dutta Deepashree , Jucker Martin , Sherwood Steven C. , Meissner Katrin J. , Sen Gupta Alex , Zhu Jiang 
Published: November 2023

AbstractProxy data suggest that the early Eocene (∼56–47.8 million years ago) was characterized by a much weaker equator-to-pole temperature gradient than today. However, general circulation models consistently underestimate high-latitude temperatures indicated by proxy records, suggesting that they may miss important processes. Previous studies hypothesized that wintertime polar stratospheric clouds may have played an important role in Arctic warming through greenhouse forcing, but these studies did not consider the effects of atmospheric chemistry or the early Eocene topography. Here we examine these factors using a high-top atmospheric model with interactive chemistry. The lower orography in the low- to mid-latitude Northern Hemisphere early Eocene weakens the stratospheric circulation which, in combination with sufficiently high methane concentrations, leads to a substantial increase in polar stratospheric clouds in the Arctic winter. Furthermore, an increase in early Eocene polar stratospheric clouds due to a 16- to 64-fold higher than pre-industrial methane concentration results in a radiative forcing larger than the direct greenhouse effect from the methane itself. This polar stratospheric cloud-induced radiative forcing could cause up to 7.4 K of Arctic surface warming. These results point to the potential for nonlinear interactions between individual forcings.
Improved high-quality reference genome of red drum facilitates the processes of resistance-related gene exploration
Authors: Xiao Yongshuang , Liu Jing , Wei Jiehong , Xiao Zhizhong , Li Jun , Ma Yuting 
Published: November 2023

AbstractSciaenops ocellatus is among the most important artificially introduced farmed fish across 11 countries and regions. However, the frequent occurrence of extreme weather events and breeding escapes have placed great pressure on local marine biodiversity and ecosystems. We reported the de novo assembly and annotation with a contig N50 of 28.30 Mb using PacBio HiFi sequencing and Hi-C technologies, which resulted in a 283-fold increase in contig N50 length and improvement in continuity and quality in complex repetitive region for S. ocellatus compared to the previous version. In total, 257.36 Mb of repetitive sequences accounted for 35.48% of the genome, and 22,845 protein-coding genes associated with a BUSCO value of 98.32%, were identified by genome annotation. Moreover, 54 hub genes rapidly responding to hypoosmotic stress were identified by WGCNA. The high-quality chromosome-scale S. ocellatus genome and candidate resistance-related gene sets will not only provide a genomic basis for genetic improvement via molecular breeding, but will also lay an important foundation for investigating the molecular regulation of rapid responses to stress.
Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan
Authors: Chou Jui-Feng , Wu Jian-Sheng , Chen Yi-Ling , Chen San-Ni 
Published: November 2023

AbstractGiven the rising prevalence of patients with diabetes and increasing treatment burden for patients with vision-threatening diabetic macular edema (DME), we aimed to explore the efficacy of modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor (VEGF) therapy under the Taiwan National Insurance Bureau reimbursement policy. We obtained data on 69 eyes treated with initial 4-monthly intravitreal injections of aflibercept or ranibizumab, plus individualized treat-and-extend regimen. At 12 months, the mean (SD) change in LogMAR best corrected visual acuity from baseline was − 0.28 (0.31) in all eyes, while that in the aflibercept and ranibizumab groups were − 0.30 (0.34) and − 0.25 (0.28), respectively. Central retinal thickness decreased by 137.2 (122.4) in all eyes, 138.1 (134.2) in the aflibercept group, and 136.2 (110.9) in the ranibizumab group. Additionally, the aflibercept group had a lower mean number of injections than the ranibizumab group (8.5 vs. 8.7). The last extended dosing interval of > 12 weeks was 31.0% and 16.7% of the eyes in the aflibercept and ranibizumab groups, respectively. The modified anti-VEGF regimens effectively managed DME in terms of functional and anatomical outcomes, and efficiently reduced the healthcare burden by reducing the number of injections and extending treatment intervals within 12 months.
Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system
Authors: Asano Hiroto , Tian Yu-Shi , Hatabu Asuka , Takagi Tatsuya , Ueda Mikiko , Ikeda Kenji 
Published: November 2023

AbstractMonoamine oxidase B (MAO-B) inhibitors are used to control Parkinson’s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.