bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA
Authors: Sen Ayesha , Kallabis Sebastian , Gaedke Felix , Jüngst Christian , Boix Julia , Nüchel Julian , Maliphol Kanjanamas , Hofmann Julia , Schauss Astrid C. , Krüger Marcus , Wiesner Rudolf J. , Pla-Martín David 
Published: November 2022

AbstractUnderstanding the mechanisms governing selective turnover of mutation-bearing mtDNA is fundamental to design therapeutic strategies against mtDNA diseases. Here, we show that specific mtDNA damage leads to an exacerbated mtDNA turnover, independent of canonical macroautophagy, but relying on lysosomal function and ATG5. Using proximity labeling and Twinkle as a nucleoid marker, we demonstrate that mtDNA damage induces membrane remodeling and endosomal recruitment in close proximity to mitochondrial nucleoid sub-compartments. Targeting of mitochondrial nucleoids is controlled by the ATAD3-SAMM50 axis, which is disrupted upon mtDNA damage. SAMM50 acts as a gatekeeper, influencing BAK clustering, controlling nucleoid release and facilitating transfer to endosomes. Here, VPS35 mediates maturation of early endosomes to late autophagy vesicles where degradation occurs. In addition, using a mouse model where mtDNA alterations cause impairment of muscle regeneration, we show that stimulation of lysosomal activity by rapamycin, selectively removes mtDNA deletions without affecting mtDNA copy number, ameliorating mitochondrial dysfunction. Taken together, our data demonstrates that upon mtDNA damage, mitochondrial nucleoids are eliminated outside the mitochondrial network through an endosomal-mitophagy pathway. With these results, we unveil the molecular players of a complex mechanism with multiple potential benefits to understand mtDNA related diseases, inherited, acquired or due to normal ageing.
An integrated platinum-nanocarbon electrocatalyst for efficient oxygen reduction
Authors: Huang Lei , Wei Min , Qi Ruijuan , Dong Chung-Li , Dang Dai , Yang Cheng-Chieh , Xia Chenfeng , Chen Chao , Zaman Shahid , Li Fu-Min , You Bo , Xia Bao Yu 
Published: November 2022

AbstractEfficient and robust platinum-carbon electrocatalysts are of great significance for the long-term service of high-performance fuel cells. Here, we report a Pt alloy integrated in a cobalt-nitrogen-nanocarbon matrix by a multiscale design principle for efficient oxygen reduction reaction. This Pt integrated catalyst demonstrates an increased mass activity, 11.7 times higher than that of commercial Pt catalyst, and retains a stability of 98.7% after 30,000 potential cycles. Additionally, this integrated catalyst delivers a current density of 1.50 A cm−2 at 0.6 V in the hydrogen-air fuel cell and achieves a power density of 980 mW cm−2. Comprehensive investigations demonstrate that the synergistic contribution of components and structure in the platinum-carbon integrated catalyst is responsible for the high-efficiency ORR in fuel cells.
Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51
Authors: Heijink Anne Margriet , Stok Colin , Porubsky David , Manolika Eleni Maria , de Kanter Jurrian K. , Kok Yannick P. , Everts Marieke , de Boer H. Rudolf , Audrey Anastasia , Bakker Femke J. , Wierenga Elles , Tijsterman Marcel , Guryev Victor , Spierings Diana C. J. , Knipscheer Puck , van Boxtel Ruben , Ray Chaudhuri Arnab , Lansdorp Peter M. , van Vugt Marcel A. T. M. 
Published: November 2022

AbstractSister chromatid exchanges (SCEs) are products of joint DNA molecule resolution, and are considered to form through homologous recombination (HR). Indeed, SCE induction upon irradiation requires the canonical HR factors BRCA1, BRCA2 and RAD51. In contrast, replication-blocking agents, including PARP inhibitors, induce SCEs independently of BRCA1, BRCA2 and RAD51. PARP inhibitor-induced SCEs are enriched at difficult-to-replicate genomic regions, including common fragile sites (CFSs). PARP inhibitor-induced replication lesions are transmitted into mitosis, suggesting that SCEs can originate from mitotic processing of under-replicated DNA. Proteomics analysis reveals mitotic recruitment of DNA polymerase theta (POLQ) to synthetic DNA ends. POLQ inactivation results in reduced SCE numbers and severe chromosome fragmentation upon PARP inhibition in HR-deficient cells. Accordingly, analysis of CFSs in cancer genomes reveals frequent allelic deletions, flanked by signatures of POLQ-mediated repair. Combined, we show PARP inhibition generates under-replicated DNA, which is processed into SCEs during mitosis, independently of canonical HR factors.
Sharp-wave ripple doublets induce complex dendritic spikes in parvalbumin interneurons in vivo
Authors: Judák Linda , Chiovini Balázs , Juhász Gábor , Pálfi Dénes , Mezriczky Zsolt , Szadai Zoltán , Katona Gergely , Szmola Benedek , Ócsai Katalin , Martinecz Bernadett , Mihály Anna , Dénes Ádám , Kerekes Bálint , Szepesi Áron , Szalay Gergely , Ulbert István , Mucsi Zoltán , Roska Botond , Rózsa Balázs 
Published: November 2022

AbstractNeuronal plasticity has been shown to be causally linked to coincidence detection through dendritic spikes (dSpikes). We demonstrate the existence of SPW-R-associated, branch-specific, local dSpikes and their computational role in basal dendrites of hippocampal PV+ interneurons in awake animals. To measure the entire dendritic arbor of long thin dendrites during SPW-Rs, we used fast 3D acousto-optical imaging through an eccentric deep-brain adapter and ipsilateral local field potential recording. The regenerative calcium spike started at variable, NMDA-AMPA-dependent, hot spots and propagated in both direction with a high amplitude beyond a critical distance threshold (~150 µm) involving voltage-gated calcium channels. A supralinear dendritic summation emerged during SPW-R doublets when two successive SPW-R events coincide within a short temporal window (~150 ms), e.g., during more complex association tasks, and generated large dSpikes with an about 2.5-3-fold amplitude increase which propagated down to the soma. Our results suggest that these doublet-associated dSpikes can work as a dendritic-level temporal and spatial coincidence detector during SPW-R-related network computation in awake mice.
Functionalized graphene grids with various charges for single-particle cryo-EM
Authors: Lu Ye , Liu Nan , Liu Yongbo , Zheng Liming , Yang Junhao , Wang Jia , Jia Xia , Zi Qinru , Peng Hailin , Rao Yu , Wang Hong-Wei 
Published: November 2022

AbstractA major hurdle for single particle cryo-EM in structural determination lies in the specimen preparation impaired by the air-water interface (AWI) and preferential particle-orientation problems. In this work, we develop functionalized graphene grids with various charges via a dediazoniation reaction for cryo-EM specimen preparation. The graphene grids are paraffin-assistant fabricated, which appear with less contaminations compared with those produced by polymer transfer method. By applying onto three different types of macromolecules, we demonstrate that the high-yield charged graphene grids bring macromolecules away from the AWI and enable adjustable particle-orientation distribution for more robust single particle cryo-EM structural determination.
Designing receptor agonists with enhanced pharmacokinetics by grafting macrocyclic peptides into fragment crystallizable regions
Authors: Sakai Katsuya , Sugano-Nakamura Nozomi , Mihara Emiko , Rojas-Chaverra Nichole Marcela , Watanabe Sayako , Sato Hiroki , Imamura Ryu , Voon Dominic Chih-Cheng , Sakai Itsuki , Yamasaki Chihiro , Tateno Chise , Shibata Mikihiro , Suga Hiroaki , Takagi Junichi , Matsumoto Kunio 
Published: November 2022

AbstractShort half-lives in circulation and poor transport across the blood–brain barrier limit the utility of cytokines and growth factors acting as receptor agonists. Here we show that surrogate receptor agonists with longer half-lives in circulation and enhanced transport rates across the blood–brain barrier can be generated by genetically inserting macrocyclic peptide pharmacophores into the structural loops of the fragment crystallizable (Fc) region of a human immunoglobulin. We used such ‘lasso-grafting’ approach, which preserves the expression levels of the Fc region and its affinity for the neonatal Fc receptor, to generate Fc-based protein scaffolds with macrocyclic peptides binding to the receptor tyrosine protein kinase Met. The Met agonists dimerized Met, inducing biological responses that were similar to those induced by its natural ligand. Moreover, lasso-grafting of the Fc region of the mouse anti-transferrin-receptor antibody with Met-binding macrocyclic peptides enhanced the accumulation of the resulting Met agonists in brain parenchyma in mice. Lasso-grafting may allow for designer protein therapeutics with enhanced stability and pharmacokinetics.
A structural biology community assessment of AlphaFold2 applications
Authors: Akdel Mehmet , Pires Douglas E. V. , Pardo Eduard Porta , Jänes Jürgen , Zalevsky Arthur O. , Mészáros Bálint , Bryant Patrick , Good Lydia L. , Laskowski Roman A. , Pozzati Gabriele , Shenoy Aditi , Zhu Wensi , Kundrotas Petras , Serra Victoria Ruiz , Rodrigues Carlos H. M. , Dunham Alistair S. , Burke David , Borkakoti Neera , Velankar Sameer , Frost Adam , Basquin Jérôme , Lindorff-Larsen Kresten , Bateman Alex , Kajava Andrey V. , Valencia Alfonso , Ovchinnikov Sergey , Durairaj Janani , Ascher David B. , Thornton Janet M. , Davey Norman E. , Stein Amelie , Elofsson Arne , Croll Tristan I. , Beltrao Pedro 
Published: November 2022

AbstractMost proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.
Characterization of four mitochondrial genomes from superfamilies Noctuoidea and Hyblaeoidea with their phylogenetic implications
Authors: Shah Rauf Ahmad , Riyaz Muzafar , Ignacimuthu Savarimuthu , Sivasankaran Kuppusamy 
Published: November 2022

AbstractIn the present study, the newly sequenced mitogenomes of three Noctuoid and one Hyblaeoid (Insecta: Lepidoptera) species were annotated based on next-generation sequence data. The complete mitogenome lengths ofOraesia emarginata, Actinotia polyodon, Odontodes seranensis,andHyblaea puerawere 16,668 bp, 15,347 bp, 15,419 bp, and 15,350 bp, respectively. These mitogenomes were found to encode 37 typical mitochondrial genes (13 protein-coding, 22 transfer RNA, 2 ribosomal RNA) and a control region, similar to most Lepidoptera species. Maximum likelihood (ML) methods and Bayesian inference (BI) were used to reconstruct the phylogenetic relationships of the moths. This study showed the relationships of Noctuoid families as follows: (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))). Furthermore, the speciesH. puerawas separately clustered from the Noctuoidea member groups. Till now, the species from the superfamily Hyblaeoidea have not been discussed for their phylogenetic relationships. In this study, the complete mitochondrial genome of one species from the superfamily Hyblaeoidea was analysed.
Photosynthetic modulation during the diurnal cycle in a unicellular diazotrophic cyanobacterium grown under nitrogen-replete and nitrogen-fixing conditions
Authors: Liberton Michelle , Biswas Sandeep , Pakrasi Himadri B. 
Published: November 2022

AbstractCyanobacteria are the only oxygenic photosynthetic organisms that can fix nitrogen. In diazotrophic cyanobacteria, the regulation of photosynthesis during the diurnal cycle is hypothesized to be linked with nitrogen fixation and involve the D1 protein isoform PsbA4. The amount of bioavailable nitrogen has a major impact on productivity in aqueous environments. In contrast to low- or nitrogen-fixing (−N) conditions, little data on photosynthetic regulation under nitrogen-replete (+ N) conditions are available. We compared the regulation of photosynthesis under −N and + N conditions during the diurnal cycle in wild type and a psbA4 deletion strain of the unicellular diazotrophic cyanobacterium Cyanothece sp. ATCC 51142. We observed common changes to light harvesting and photosynthetic electron transport during the dark in + N and −N conditions and found that these modifications occur in both diazotrophic and non-diazotrophic cyanobacteria. Nitrogen availability increased PSII titer when cells transitioned from dark to light and promoted growth. Under −N conditions, deletion of PsbA4 modified charge recombination in dark and regulation of PSII titer during dark to light transition. We conclude that darkness impacts the acceptor-side modifications to PSII and photosynthetic electron transport in cyanobacteria independently of the nitrogen-fixing status and the presence of PsbA4.
First report of glyphosate-resistant downy brome (Bromus tectorum L.) in Canada
Authors: Geddes Charles M. , Pittman Mattea M. 
Published: November 2022

AbstractGlyphosate is the most used herbicide worldwide, and is an important source of economical weed control in glyphosate-resistant crops, and conservation tillage systems, among other uses. Downy brome (Bromus tectorum L.), otherwise known as cheatgrass, is a highly invasive winter-annual grass weed in cropping systems, pastureland, and naturalized or ruderal areas in western North America. In 2021, a downy brome population remained uncontrolled following four applications of glyphosate in a glyphosate-resistant canola (Brassica napus L.) field located in Taber County, Alberta, Canada. All individuals from the subsequent generation of the population survived glyphosate treatment at the typical field rate (900 g ae ha−1). In dose-response bioassays, the putative glyphosate-resistant population exhibited 10.6- to 11.9-fold, 7.7- to 8.7-fold, 7.8- to 8.8-fold, and 8.3- to 9.5-fold resistance to glyphosate based on plant survival, visible control, and biomass fresh weight and dry weight, respectively, compared with two susceptible populations 21 days after treatment. Estimated glyphosate rates for 80% control of this population ranged from 2795 to 4511 g ae ha−1; well above common usage rates. This downy brome population represents the first glyphosate-resistant grass weed confirmed in Canada, and the second weed species exhibiting glyphosate resistance in the Canadian prairie region.
High-throughput analysis of tissue microarrays using automated desorption electrospray ionization mass spectrometry
Authors: Morato Nicolás M. , Brown Hannah Marie , Garcia Diogo , Middlebrooks Erik H. , Jentoft Mark , Chaichana Kaisorn , Quiñones-Hinojosa Alfredo , Cooks R. Graham 
Published: November 2022

AbstractTissue microarrays (TMAs) are commonly used for the rapid analysis of large numbers of tissue samples, often in morphological assessments but increasingly in spectroscopic analysis, where specific molecular markers are targeted via immunostaining. Here we report the use of an automated high-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS) for the rapid generation and online analysis of high-density (6144 samples/array) TMAs, at rates better than 1 sample/second. Direct open-air analysis of tissue samples (hundreds of nanograms) not subjected to prior preparation, plus the ability to provide molecular characterization by tandem mass spectrometry (MS/MS), make this experiment versatile and applicable to both targeted and untargeted analysis in a label-free manner. These capabilities are demonstrated in a proof-of-concept study of frozen brain tissue biopsies where we showcase (i) a targeted MS/MS application aimed at identification of isocitrate dehydrogenase mutation in glioma samples and (ii) an untargeted MS tissue type classification using lipid profiles and correlation with tumor cell percentage estimates from histopathology. The small sample sizes and large sample numbers accessible with this methodology make for a powerful analytical system that facilitates the identification of molecular markers for later use in intraoperative applications to guide precision surgeries and ultimately improve patient outcomes.
Design and experimental research of a novel deep-sea self-sustaining profiling float for observing the northeast off the Luzon Island
Authors: Wang Qiang , Qiu Zurong , Yang Shaobo , Li Hongyu , Li Xingfei 
Published: November 2022

AbstractTo understand the physical ocean laws of ocean circulation in the deep ocean below 2000 m, a profiling float named FUXING is presented to meet the deep-ocean observation requirements at a depth of 4000 m. First, to meet the low energy consumption and buoyancy regulation stability of the profiling float, the low–power buoyancy adjustment process of FUXING is effectively solved by introducing the external seawater pressure as the driving force. Then, to reduce the energy consumption of the single profile for the profiling float, the optimization of the oil draining adjustment mode in the floating process is studied. Simultaneously, a buoyancy-driven system characterization test was performed to examine the buoyancy adjustment of FUXING. When the frequency of oil draining is 15 times, the total energy consumption of FUXING is the lowest. Finally, FUXING was deployed in the northeast off the Luzon Island to validate the feasibility and reliability. The at-sea experiments indicated that the optimized oil draining adjustment mode can reduce the total energy consumption in the floating process by more than 20%. The profile data showed that the outer sea water gradually mixes with the South China Sea water after passing through the northeast off the Luzon Island.
Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients
Authors: Iwadare Takanobu , Kimura Takefumi , Tanaka Naoki , Yamazaki Tomoo , Wakabayashi Shun-ichi , Okumura Taiki , Kobayashi Hiroyuki , Yamashita Yuki , Pydi Sai P. , Nakajima Tomoyuki , Iwaya Mai , Sugiura Ayumi , Joshita Satoru , Uehara Takeshi , Umemura Takeji 
Published: November 2022

AbstractAmong several secreted glycoproteins belonging to the thrombospondin family, thrombospondin 2 (TSP2) is involved in various functions, including collagen/fibrin formation. Liver/serum TSP2 levels have been correlated to liver fibrosis stage and disease activity in nonalcoholic fatty liver disease. This study investigated whether serum TSP2 was associated with clinicopathological features in hepatitis C virus (HCV)-infected patients as well. A total of 350 patients with HCV who had undergone liver biopsy were retrospectively enrolled and divided into a discovery cohort (n = 270) and a validation cohort (n = 80). In the discovery cohort, serum TSP2 levels were moderately correlated with both liver fibrosis stage (r = 0.426, P < 0.0001) and activity grade (r = 0.435, P < 0.0001). The area under the receiver operating characteristic curve of TSP2 for predicting severe fibrosis (≥ F3) was 0.78 and comparable to or better than those of autotaxin (0.78), FIB-4 index (0.78), and APRI (0.76). The discovery cohort findings were closely replicated in the validation cohort. Moreover, comprehensive liver genetic analysis of HCV-infected patients confirmed that the expression of the THBS2 gene encoding TSP2 was significantly higher in severely fibrotic F4 than in F1 patients. Circulating TSP2 levels may reflect the severity of hepatic fibrosis/inflammation in HCV-infected patients.
Ship wave patterns on floating ice sheets
Authors: Johnsen Kristoffer , Kalisch Henrik , Părău Emilian I. 
Published: November 2022

AbstractThis paper aims to explore the response of a floating icesheet to a load moving in a curved path. We investigate the effect of turning on the wave patterns and strain distribution, and explore scenarios where turning increases the wave amplitude and strain in the ice, possibly leading to crack formation, fracturing and eventual ice failure. The mathematical model used here is the linearized system of differential equations introduced in Dinvay et al. (J. Fluid Mech. 876:122–149, 2019). The equations are solved using the Fourier transform in space, and the Laplace transform in time. The model is tested against existing results for comparison, and several cases of load trajectories involving turning and decelerating are tested.
The impact of resilience as a protective factor on Health-Related Quality of Life’s psychological dimensions among adolescents who experience peer victimization
Authors: Martín-Pérez Ángela de Lourdes , Morán-Sánchez Inés , Gascón-Cánovas Juan José 
Published: November 2022

AbstractPeer victimization have a negative impact on Health-Related Quality of Life (HRQoL) during adolescence, however some personal skills such a person's resilience could play a significant role in this relationship. In this context, this study aims to analyse if resilience is a moderator of the relation between peer victimization and HRQoL’s psychological dimensions. Sociodemographic data, peer victimization, psychological domains of HRQoL and resilience were measures in a sample of 1428 secondary school students using the following scales: “Adolescent Peer Relations Instrument-Bullying”, “KIDSCREEN-52” and “Brief Resilient Coping Scale. Different multivariate analyses were carried out using linear regression. PROCESS tool was used to examine the moderating role of resilience, with John-Neyman post-hoc approach to quantify moderation. Results suggest that resilience could moderate the association between physical (β =  − 0.0021; p = 0.025) and verbal victimization (β =  − 0.0018; p = 0.024) and the “Mood and Emotions” dimension of adolescents’ HRQoL. Nevertheless, this regulating influence appears to be faint (∆R2 0.004). Resilience showed no moderating effect between social victimization and psychological dimensions of HRQoL. We concluded that resilience could function as a protective factor that weakly regulates the negative association between physical and verbal victimization and the psychological sphere of adolescents’ HRQoL.