bluuebunny/crossref_metadata_2025_split huggingface dataset:
SBT-272 improves TDP-43 pathology in the ALS motor cortex by modulating mitochondrial integrity, motility, and function
Authors: Gautam Mukesh , Genç Barış , Helmold Benjamin , Ahrens Angela , Kuka Janis , Makrecka-Kuka Marina , Günay Aksu , Koçak Nuran , Aguilar-Wickings Izaak R. , Keefe Dennis , Zheng Guozhu , Swaminathan Suchitra , Redmon Martin , Zariwala Hatim A. , Özdinler P. Hande 
Published: October 2022

AbstractMitochondrial defects are one of the common underlying causes of neuronal vulnerability in motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is the most common proteinopathy in ALS. Disrupted inner mitochondrial membrane (IMM) reported in the upper motor neurons (UMNs) of ALS patients with TDP-43 pathology is recapitulated in the UMNs of well-characterized mutant hTDP-43 mouse models of ALS. The construct validity, such as common cellular pathology in mice and human, offers a unique opportunity to test treatment strategies that may translate. SBT-272 is a well-tolerated brain-penetrant small molecule that stabilizes cardiolipin, a phospholipid found in IMM, thereby restoring mitochondrial structure and respiratory function. We investigated whether SBT-272 can improve IMM structure and health in UMNs diseased with TDP-43 pathology in our well-characterized UMN reporter line for ALS. We found that SBT-272 significantly improved mitochondrial structural integrity and restored mitochondrial motility and function. This led to improved health of diseased UMNsin vitro.In comparison to edaravone and AMX0035, SBT-272 appeared more effective in restoring health of diseased UMNs. Chronic treatment of SBT-272 for sixty days starting at an early symptomatic stage of the diseasein vivoled to a reduction in astrogliosis, microgliosis, and retention of UMN degeneration in the ALS motor cortex. Our results underscore the therapeutic potential of SBT-272, especially within the context of TDP-43 pathology and mitochondrial dysfunction.HighlightsEarly and progressive upper motor neuron (UMN) degeneration defines ALS pathologyMitochondrial defects are prominent and common in UMNs with TDP-43 pathologySBT-272 treatment improves mitochondrial stability, mobility and functionSBT-272 treatment reduces astrogliosis, microgliosis and improves UMN health
Cortical-wide impairment of “The Glymphatic system” after focal brain injury
Authors: Azuma M. , Lee H. , Shinzaki K. , Yamane R. , Morita M. 
Published: October 2022

AbstractIn peripheral tissues, cells are maintained in the interstitial fluid that flows from capillaries to lymph system. However, the brain has no lymphatic capillaries, and the actual state of the interstitial fluid has long been unknown. Recently, a glymphatic system has been proposed in which part of the cerebrospinal fluid flowing on the surface of brain tissue enters the brain parenchyma via the peri-arterial space, becomes interstitial fluid, and then flows out again from the peri-venous space. Brain injury due to head contusion or stroke is thought to impair the intracerebral circulation and aggravate the extracellular environment, but the actual situation is unknown. Therefore, in this study, we examined the effects of focal brain tissue damage on intracerebral circulation using the light-injured mouse, an originally developed closed head injury model. In light-injured mice, the injury-making process does not affect intracerebral circulation because the cranium is maintained. However, this method has quantitative problems, so we developed a method to image cerebrospinal fluid and blood vessels from the surface of the cerebral cortex. After examining different injury sites and different time periods after injury, it was found that intracerebral circulation was reduced to the same extent on the ipsilateral and contralateral sides of the injury at one-week post-injury. This intracerebral circulatory deficit was still partially present at four-weeks post-injury. These results indicate that the intracerebral circulation is extensively impaired by local injury and neurodegenerative diseases.
Panomics reveals patient-individuality as the major driver for colorectal cancer progression
Authors: Praus Friederike , Künstner Axel , Sauer Thorben , Kohl Michael , Kern Katharina , Deichmann Steffen , Végvári Ákos , Keck Tobias , Busch Hauke , Habermann Jens K , Gemoll Timo 
Published: October 2022

AbstractColorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases. The prognosis of CRC considerably depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aims to integrate genomic, transcriptomic, and proteomic analyses to identify significant expression differences during colorectal progression using a unique set of paired patient samples concerning tumor heterogeneity.We analyzed fresh-frozen tissue samples of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from same patients prepared under strict cryogenic conditions. While somatic mutations of known cancer-related genes were analyzed using Illumina’s TruSeq Amplicon Cancer Panel, the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC-MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated using differential expression results.While panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumor and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with a patient-individual transcriptome and proteome.In conclusion, the results highlight the importance of inter- and intra-tumor heterogeneity alongside the individual, patient-paired evaluation for clinical studies. Next to changes among groups reflecting colorectal cancer progression, we identified significant expression differences between patient-individual normal colon mucosa, primary tumor, and liver metastasis, which could speed up the implementation of precision oncology in the future.
Feasibility and preliminary effectiveness of behavioral activation for cancer patients with depression
Authors: Hirayama Takatoshi , Ogawa Yuko , Yanai Yuko , Shindo Akie , Tanaka Moeko , Suzuki Shin-ichi 
Published: October 2022

AbstractBackgroundBehavioral activation (BA) is a psychotherapy that directly approaches patients’ most valued daily activities. BA may be particularly useful for treating depression in patients with cancer, but there is insufficient evidence in this population. This study aimed to verify the feasibility and preliminary effectiveness of BA for patients with depression with all types and stages of cancer.MethodsThis pre–post study without a control group was conducted in patients with cancer and depression. The program completion rate was compared with those of previous studies to verify feasibility. To examine the preliminary effectiveness of BA, outcomes were evaluated four times: before and immediately after the program, and 2 weeks and 3 months after the program ended. The primary outcome was the remission rate of depression determined using a binomial test and the 17-item version of the GRID Hamilton Rating Scale for Depression (HAMD17). Secondary outcomes were self-reported depression, anxiety, quality of life, changes in behavior, values, and perceived reward of activity and environmental factors. Pre- and post-program data were compared using paired-samples t-tests, and data obtained at four time points were analyzed using one-way repeated measures analysis of variance. Hedge’s g was computed for calculating effect sizes.ResultsParticipants were recruited from February 2018 to January 2022. Of the 68 patients who were initially recruited, 32 were registered. The completion rate was 75% (24/32), which was similar to previous studies. The total HAMD17 score significantly improved after the program with large effect sizes (Hedge’s g =1.95). The remission rate of depression was 62.5% (20/32), which was above the defined threshold value (30%). All but two secondary outcomes significantly improved after the program (p<0.05).ConclusionsThis study suggested the feasibility and preliminary effectiveness of BA for patients with depression. To establish further evidence for the use of BA in patients with cancer, randomized controlled trials are needed.Trial RegistrationUniversity Hospital Medical Information Network (UMIN CTR) UMIN000036104. Registered 6 March 2019 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041129
Biological fractionation of lithium isotopes by cellular Na+/H+ exchangers unravels fundamental transport mechanisms
Authors: Poet Mallorie , Vigier Nathalie , Bouret Yann , Jarretou Gisèle , Bendahhou Saïd , Montanes Maryline , Thibon Fanny , Counillon Laurent 
Published: October 2022

SUMMARYLithium (Li) has a wide range of uses in science, medicine and industry but its isotopy is underexplored, except in nuclear science and in geoscience. 6Li and 7Li isotopic ratio exhibits the second largest variation on Earth’s surface and constitutes a widely used tool for reconstructing past oceans and climates. As large variations have been measured in mammalian organs, plants or marine species, and as 6Li elicits stronger effects than natural Li (~95% 7Li) a central issue is the identification and quantification of biological influence of Li isotopes distribution. We show here that membrane ion channels and Na+-Li+/H+ exchangers (NHEs), strongly fractionate Li isotopes. This systematic 6Li enrichment is driven by membrane potential for channels, and by intracellular pH for NHEs, where it displays cooperativity, a hallmark of dimeric transport. Evidencing that transport proteins discriminate between isotopes differing by one neutron, opens new avenues for transport mechanisms, Li physiology, and paleoenvironments.
OligoArchive-DSM: Columnar Design for Error-Tolerant Database Archival using Synthetic DNA
Authors: Marinelli Eugenio , Yan Yiqing , Magnone Virginie , Dumargne Marie-Charlotte , Barbry Pascal , Heinis Thomas , Appuswamy Raja 
Published: October 2022

ABSTRACTThe surge in demand for cost-effective, durable long-term archival media, coupled with density limitations of contemporary magnetic media, has resulted in synthetic DNA emerging as a promising new alternative. Today, the limiting factor for DNA-based data archival is the cost of writing (synthesis) and reading (sequencing) DNA. Newer techniques that reduce the cost often do so at the expense of reliability, as they introduce complex, technology-specific error patterns. In order to deal with such errors, it is important to design efficient pipelines that can carefully use redundancy to mask errors without amplifying overall cost. In this paper, we present OligoArchive-DSM (OA-DSM), an end-to-end DNA archival pipeline that can provide error-tolerant data storage at low read/write costs. Central to OA-DSM is a database-inspired columnar encoding technique that makes it possible to improve efficiency by enabling integrated decoding and consensus calling during data restoration.
C1orf112 is a novel regulator of interstrand crosslink that decreases FIGNL1-RAD51 interaction
Authors: Pinedo-Carpio Edgar , Dessapt Julien , Villot Romain , Sacre Lauralicia , Malina Abba , Boulais Jonathan , Lavoie Elise G. , Luo Vincent , Lazaratos Ana-Maria , Côté Jean-François , Mallette Frédérick , Guarné Alba , Fradet-Turcotte Amelie , Orthwein Alexandre 
Published: October 2022

ABSTRACTInterstrand DNA crosslinks (ICLs) represent complex lesions that block essential biological processes, including DNA replication, recombination, and transcription. Several pathways have been involved in ICL repair, in particular nucleotide excision repair (NER), translesion DNA synthesis (TLS), Fanconi anemia (FA), and homologous recombination (HR). Still, the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genome-wide screening, we identified the poorly characterized C1orf112 (also known as Apolo1) as a novel sensitizer to the clinically relevant ICL-inducing agent mafosfamide. Consistently, we noted that low expression of C1orf112 correlates with increased sensitivity to a series of ICL agents and PARP inhibitors in a panel of cell lines. We showed that lack of C1orf112 does not impact the initial recruitment and ubiquitylation of FANCD2 at the ICL site but rather impairs the resolution of RAD51 from ICL-induced DSBs, thereby compromising homology-directed DNA repair pathways. Our proximal mapping of C1orf112 protein neighbours coupled to structure-function analysis revealed that C1orf112, through its WCF motif, forms a complex with the N-terminal domain of the AAA+ ATPase FIGNL1 and regulates the interaction of FIGNL1 with RAD51. Our work establishes the C1orf112-FIGNL1 complex as an integral part of the HR-mediated response to ICLs by regulating the unloading of RAD51 during ICL repair.
Mitochondrial Function is Preserved Under Cysteine Starvation via Glutathione Catabolism in NSCLC
Authors: Ward Nathan P. , Yoon Sang Jun , Flynn Tyce , Sherwood Amanda , Madej Juliana , DeNicola Gina M. 
Published: October 2022

AbstractCysteine metabolism occurs across cellular compartments to support diverse biological functions and prevent the induction of ferroptosis. Though the disruption of cytosolic cysteine metabolism is implicated in this form of cell death, it is unknown whether the substantial cysteine metabolism resident within the mitochondria is similarly pertinent to ferroptosis. Here, we show that despite the rapid depletion of intracellular cysteine upon loss of extracellular cystine, cysteine-dependent synthesis of Fe-S clusters persists in the mitochondria of lung cancer cells. This promotes a retention of respiratory function and a maintenance of the mitochondrial redox state. Under these limiting conditions, we find that mitochondrial glutathione sustains the function of the Fe-S proteins critical to oxidative metabolism. This is achieved through CHAC1 catabolism of the cysteine-containing tripeptide within the mitochondrial matrix. We find that disrupting Fe-S cluster synthesis under cysteine restriction protects against the induction of ferroptosis, suggesting that the preservation of mitochondrial function is antagonistic to survival under starved conditions. Overall, our findings implicate mitochondrial cysteine metabolism in the induction of ferroptosis and reveal a novel mechanism of mitochondrial resilience in response to nutrient stress.
Farnesoid X Receptor suppresses lipid peroxidation and ferroptosis
Authors: Tschuck Juliane , Theilacker Lea , Rothenaigner Ina , Weiß Stefanie A. I. , Akdogan Banu , Müller Constanze , Graf Roman , Brandner Stefanie , Pütz Christian , Rieder Tamara , Schmitt-Kopplin Philippe , Zischka Hans , Schorpp Kenji , Hadian Kamyar 
Published: October 2022

ABSTRACTObjectiveFerroptosis is a regulated cell death modality that occurs upon iron-dependent lipid peroxidation. The recent decade of research has uncovered many regulators driving ferroptosis as well as cellular gatekeepers preventing ferroptosis. Yet, many processes and networks remain to be elucidated.Methods and resultsIn this study, we performed a chemical screen using small molecules with known mode of action and identified two agonists (Turofexorate and Fexaramine) of the nuclear receptor Farnesoid X Receptor (FXR), also known as NR1H4, to suppress ferroptosis, but not apoptosis or necroptosis. Further, we demonstrate that in liver cells with high FXR protein levels, inhibition of FXR sensitizes cells to undergo ferroptotic cell death, while activation of FXR inhibits ferroptosis. Importantly, FXR also inhibits ferroptosis in ex vivo primary mouse hepatocytes. Activation of FXR by Turofexorate and Fexaramine significantly reduces lipid peroxidation. Mechanistically, overexpression of FXR or activation of FXR by bile acids upregulates the ferroptosis-inhibitory regulators FSP1, PPARα, GPX4, SCD1, and ACSL3 to reduce peroxidized lipids and to counteract ferroptosis.ConclusionIn this study, we demonstrate that activation of FXR inhibits ferroptotic cell death via upregulation of a number of ferroptosis-inhibitory proteins (FSP1, PPARα, GPX4, SCD1, and ACSL3) to reduce lipid peroxidation. Hence, modulating FXR activity may be beneficial to overcome ferroptosis-mediated degenerative diseases.
Big data analytics capabilities and green supply chain performance: investigating the moderated mediation model for green innovation and technological intensity
Authors: Al-Khatib Ayman Wael 
Published: October 2022

PurposeThis study investigates the impact of big data analytics capabilities on green supply chain performance. Moreover, it assesses the mediating effect of the green innovation and moderating effect of technological intensity.Design/methodology/approachThis study is based on primary data that were collected from the food and beverages manufacturing sector operating in Jordan. A total of 420 samples were used for the final data analysis. Data analysis was performed via structural equation modeling (SEM) using SmartPLS 3.3.9.FindingsThe results of the data analysis supported a positive relationship between big data analytics capabilities and the green supply chain performance as well as a mediating effect of green innovation. It was confirmed that technological intensity moderated the relationship of green innovation on green supply chain performance.Research limitations/implicationsThe study faced many limitations such as the method of collecting primary data, which relied on a questionnaire only and the use of cross-sectional data, as well as studying one context and in one country.Practical implicationsThe findings can guide managers and policymakers in the Jordanian food and beverage manufacturing sector on how to manage organizational capabilities related to big data analytics to enhance green supply chain performance and improve green innovation in these firms.Originality/valueThis study developed a theoretical and empirical model to investigate the relationship between big data analytics capabilities, green innovation, technological intensity and green supply chain performance. This study offers new theoretical and managerial contributions that add value to the supply chain management and innovation literature by testing the moderated mediation model of these constructs in the food and beverages manufacturing sector in Jordan.
Circuit analysis and modeling of a soft-switching pulse power supply based on full-bridge inverter for DBD application
Authors: Tang Xiongmin , Jiang Tianhong , Chen Weizheng , Lin ZhiHong , Zhou Zexin , Yongquan Chen , Zhang Miao 
Published: October 2022

Purpose
How to use a simple and classical topology to provide a high-efficiency excitation voltage for dielectric barrier discharge (DBD) loads is one of the primary problems to be solved for DBD application fields.

Design/methodology/approach
To address the issue, a set of modes that can generate a high-efficiency pulse excitation voltage in a full-bridge inverter are adopted. With the set of modes, the unique equivalent circuit of DBD loads and the parasitic parameter of the step-up transformer can be fully used. Based on the set of modes, a control strategy for the full-bridge inverter is designed. To test the performance of the power supply, a simulation model is established and an experimental prototype is made with a DBD excimer lamp.

Findings
The simulation and experimental results show that not only a high-efficiency excitation voltage can be generated for the DBD load, but also the soft switching of all power switch is realized. Besides this, with the set of modes and the proposed control strategy, the inverter can operate in a high frequency. Compared with other types of power supplies, the power supply used in the paper can fully take advantage of the potential of the excimer lamp at the same input power.

Originality/value
This work considers that how to use a simple and classical topology to provide a high-efficiency excitation voltage for DBD loads is one of the primary problems to be solved for DBD application fields.
Toward a critical technical practice in disaster risk management: lessons from designing collaboration initiatives
Authors: Lallemant David , Bicksler Rebecca , Barns Karen , Hamel Perrine , Soden Robert , Bannister Steph 
Published: October 2022

Purpose Despite decades of social science research into disasters, practice in the field continues to be informed largely from a technical perspective. The outcome is often a perpetuation of vulnerability, as narrowly defined technical interventions fail to address or recognize the ethical, historical, political and structural complexities of real-world community vulnerability and its causes. The authors propose that addressing this does not require a rejection of technical practice, but its evolution into a critical technical practice – one which foregrounds interdisciplinarity, inclusion, creativity and reflexivity, as means to question the assumptions, ideologies and delimited solutions built into the technical tools for understanding risks.Design/methodology/approach The authors present findings from three events they designed and facilitated, aimed at rethinking the engineering pedagogy and technical practice of disaster risk management. The first was a 2-day “artathon” that brought together engineers, artists and scientists to collaborate on new works of art based on disaster and climate data. The second was the Understanding Risk Field Lab, a 1-month long arts and technology un-conference exploring critical design practices, collaborative technology production, hacking and art to address complex issues of urban flooding. The third was a 4-month long virtual workshop on responsible engineering, science and technology for disaster risk management.Findings Each of these events uncovered and highlighted the benefits of interdisciplinary collaboration and reflexivity in disaster risk modeling, communication and management. The authors conclude with a discussion of the key design elements that help promote the principles of a critical technical practice.Originality/value The authors propose “critical technical practice” which foregrounds principles of interdisciplinarity, inclusion, creativity and reflexivity, as a means to question the assumptions, ideologies and delimited solutions built into the technical tools for understanding climate and disaster risk.