bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways
Authors: Wang Su Hyeon , Lee Duk-Shin , Kim Tae-Hyun , Kim Ji-Eun , Kang Tae-Cheon 
Published: September 2024

AbstractLoss of parvalbumin (PV) expressing neurons (PV neurons) is relevant to the underlying mechanisms of the pathogenesis of neurological and psychiatric diseases associated with the dysregulation of neuronal excitatory networks and brain metabolism. Although PV modulates mitochondrial morphology, volume and dynamics, it is largely unknown whether mitochondrial dynamics affect PV expression and what the molecular events are responsible for PV neuronal degeneration. In the present study, L-buthionine sulfoximine (BSO, an inhibitor of glutathione synthesis) did not degenerate PV neurons under physiological condition. However, BSO-induced oxidative stress decreased PV expression and facilitated cyclin-dependent kinase 5 (CDK5) tyrosine (Y) 15 phosphorylation, dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and glutathione peroxidase-1 (GPx1) downregulation in PV neurons. Co-treatment of roscovitine (a CDK5 inhibitor) or mitochondrial division inhibitor-1 (Mdivi-1, an inhibitor of mitochondrial fission) attenuated BSO-induced PV downregulation. WY14643 (an inducer of mitochondrial fission) reduced PV expression without affecting CDK5 Y15 phosphorylation. Following status epilepticus (SE), CDK5 Y15 phosphorylation and mitochondrial fission were augmented in PV neurons. These were accompanied by reduced GPx1-mediated inhibition of NF-κB p65 serine (S) 536 phosphorylation. N-acetylcysteine (NAC), roscovitine and Mdivi-1 ameliorated SE-induced PV neuronal degeneration by mitigating CDK5 Y15 hyperphosphorylation, aberrant mitochondrial fragmentation and reduced GPx1-mediated NF-κB inhibition. Furthermore, SN50 (a NF-κB inhibitor) alleviated SE-induced PV neuronal degeneration, independent of dysregulation of mitochondrial fission, CDK5 hyperactivation and GPx1 downregulation. These findings provide an evidence that oxidative stress may activate CDK5-DRP1- and GPx1-NF-κB-mediated signaling pathways, which would be possible therapeutic targets for preservation of PV neurons in various diseases.
Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer
Authors: Jiang Jian-zhuo , Qiao Yin-biao , Zhu Xiao-ren , Gu Qian-hui , Lu Jing-jing , Ye Zhen-yu , Xu Lu , Liu Yuan-yuan 
Published: September 2024

AbstractThe increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3’s role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3’s critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.
Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth
Authors: Sang Yong-hua , Luo Chun-ying , Huang Bing-tao , Wu Siyang , Shu Jian , Lan Chang-gong , Zhang Fuquan 
Published: September 2024

AbstractExploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.
SALL2 regulates neural differentiation of mouse embryonic stem cells through Tuba1a
Authors: Xiong Hui , Lin Bowen , Liu Junyang , Lu Renhong , Lin Zheyi , Hang Chengwen , Liu Wenjun , Zhang Lei , Ding Jie , Guo Huixin , Zhang Mingshuai , Wang Siyu , Gong Zheng , Xie Duanyang , Liu Yi , Shi Dan , Liang Dandan , Liu Zhen , Chen Yi-Han , Yang Jian 
Published: September 2024

AbstractThe spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2’s function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.
Propane wet reforming over PtSn nanoparticles on γ-Al2O3 for acetone synthesis
Authors: Ma Xinlong , Yin Haibin , Pu Zhengtian , Zhang Xinyan , Hu Sunpei , Zhou Tao , Gao Weizhe , Luo Laihao , Li Hongliang , Zeng Jie 
Published: September 2024

AbstractAcetone serves as an important solvent and building block for the chemical industry, but the current industrial synthesis of acetone is generally accompanied by the energy-intensive and costly cumene process used for phenol production. Here we propose a sustainable route for acetone synthesis via propane wet reforming at a moderate temperature of 350 oC with the use of platinum-tin nanoparticles supported on γ-aluminium oxide (PtSn/γ-Al2O3) as catalyst. We achieve an acetone productivity of 858.4 μmol/g with a selectivity of 57.8% among all carbon-based products and 99.3% among all liquid products. Detailed spectroscopic and controlled experiments reveal that the acetone is formed through a tandem catalytic process involving propene and isopropanol as intermediates. We also demonstrate facile ketone synthesis via wet reforming with the use of different alkanes (e.g., n-butane, n-pentane, n-hexane, n-heptane, and n-octane) as substrates, proving the wide applicability of this strategy.
Leptospira interrogans biofilm transcriptome highlights adaption to starvation and general stress while maintaining virulence
Authors: Davignon Grégoire , Pietrosemoli Natalia , Benaroudj Nadia , Soupé-Gilbert Marie-Estelle , Cagliero Julie , Turc Élodie , Picardeau Mathieu , Guentas Linda , Goarant Cyrille , Thibeaux Roman 
Published: September 2024

AbstractLife-threatening Leptospira interrogans navigate a dual existence: surviving in the environment and infecting mammalian hosts. Biofilm formation is presumably an important survival strategy to achieve this process. Understanding the relation between biofilm and virulence might improve our comprehension of leptospirosis epidemiology. Our study focused on elucidating Leptospira’s adaptations and regulations involved in such complex microenvironments. To determine the transcriptional profile of Leptospira in biofilm, we compared the transcriptomes in late biofilms and in exponential planktonic cultures. While genes for motility, energy production, and metabolism were downregulated, those governing general stress response, defense against metal stress, and redox homeostasis showed a significant upsurge, hinting at a tailored defensive strategy against stress. Further, despite a reduced metabolic state, biofilm disruption swiftly restored metabolic activity. Crucially, bacteria in late biofilms or resulting from biofilm disruption retained virulence in an animal model. In summary, our study highlights Leptospira’s adaptive equilibrium in biofilms: minimizing energy expenditure, potentially aiding in withstanding stresses while maintaining pathogenicity. These insights are important for explaining the survival strategies of Leptospira, revealing that a biofilm lifestyle may confer an advantage in maintaining virulence, an understanding essential for managing leptospirosis across both environmental and mammalian reservoirs.
Marine carbon sink dominated by biological pump after temperature overshoot
Authors: Koeve Wolfgang , Landolfi Angela , Oschlies Andreas , Frenger Ivy 
Published: September 2024

AbstractIn the event of insufficient mitigation efforts, net-negative CO2 emissions may be required to return climate warming to acceptable limits as defined by the Paris Agreement. The ocean acts as an important carbon sink under increasing atmospheric CO2 levels when the physico-chemical uptake of carbon dominates. However, the processes that govern the marine carbon sink under net-negative CO2 emission regimes are unclear. Here we assessed changes in marine CO2 uptake and storage mechanisms under a range of idealized temperature-overshoot scenarios using an Earth system model of intermediate complexity over centennial timescales. We show that while the fate of CO2 from physico-chemical uptake is very sensitive to future atmospheric boundary conditions and CO2 is partly lost from the ocean at times of net-negative CO2 emissions, storage associated with the biological carbon pump continues to increase and may even dominate marine excess CO2 storage on multi-centennial timescales. Our findings imply that excess carbon that is attributable to the biological carbon pump needs to be considered carefully when quantifying and projecting changes in the marine carbon sink.
Madagascar rural observatory surveys, a longitudinal dataset on household living conditions 1995–2015
Authors: Andrianjafindrainibe Velomalala Solo , Andrianirina Nicole , Bédécarrats Florent , Droy Isabelle , Dubois Jean-Luc , de Montalembert Jeanne , Rabevohitra Bako Nirina , Rafidimanana Rolland , Rasolofo Patrick , Ratovoarinony Raphaël , Ratsaramiarina Lalasoa Anjarafara Onivola , Ravelonandro Jean Dieudonné , Razanamavo Voahirana , Razafindrakoto Mireille , Rivolala Bezaka , Roubaud François , Saint-Macary Camille 
Published: September 2024

AbstractA Rural Observatory System (ROS) was established in Madagascar to address the lack of socioeconomic data on rural areas. It collected, analyzed, and disseminated data to help formulate and evaluate development policies. From 1995 to 2015, the ROS surveyed a total of 26 areas. The ROS methodology involved annual household panel surveys using consistent questionnaires supplemented by modules covering new themes. Qualitative community surveys were used to understand local features and dynamics. The site selection combined quantitative and qualitative insights to reflect the diversity of Madagascar’s rural challenges. Quality control was comprehensive, with measures such as limiting the number of daily surveyor interviews and daily field supervision. By making this data available for 21 consecutive years, along with documentation, metadata, and code with analysis examples, we aim to facilitate their discovery, assessment, and understanding by researchers, policymakers, and social organizations. To our knowledge, this is the only available data for an in-depth analysis of the situation and trends in the rural areas of Madagascar.
Non-canonical chromatin-based functions for the threonine metabolic pathway
Authors: Chik Jennifer K. , Su Xue Bessie , Klepin Stephen , Raygoza Jessica , Pillus Lorraine 
Published: September 2024

AbstractThe emerging class of multi-functional proteins known as moonlighters challenges the “one protein, one function” mentality by demonstrating crosstalk between biological pathways that were previously thought to be functionally discrete. Here, we present new links between amino acid metabolism and chromatin regulation, two biological pathways that are critical for cellular and organismal homeostasis. We discovered that the threonine biosynthetic pathway is required for the transcriptional silencing of ribosomal DNA (rDNA) in Saccharomyces cerevisiae. The enzymes in the pathway promote rDNA silencing through distinct mechanisms as a subset of silencing phenotypes was rescued with exogenous threonine. In addition, we found that a key pathway enzyme, homoserine dehydrogenase, promotes DNA repair through a mechanism involving the MRX complex, a major player in DNA double strand break repair. These data further the understanding of enzymes with non-canonical roles, here demonstrated within the threonine biosynthetic pathway, and provide insight into their roles as potential anti-fungal pharmaceutical targets.
Toxoplasma gondii infection affects the complete blood count and disturbs the markers of oxidative stress from the vital organs of wild rodents
Authors: Ijaz Maryam , Khan Asmat Ullah , Ullah Shakir , Khan Afshan , Ibenmoussa Samir , Sitotaw Baye , Dawoud Turki M. , Khan Adil , Iqbal Furhan 
Published: September 2024

AbstractRodents are the synanthropic mammals that are existing in close proximity to humans and their belongings and have the potential to act as the reservoir for a variety of parasites having zoonotic potential. Present study was designed to report the molecular prevalence and phylogenetic evaluation of Toxoplasma gondii in the blood samples of four wild rodent species [Rattus rattus (N = 122), Mus musculus (N = 64), Rattus norvegicus (N = 57) and Dryomys nitedula (N = 1)] that were trapped during May 2022 till July 2023 from three districts in Punjab (Jampur, Dera Ghazi Khan and Multan) and three districts (Upper Dir, Mardan and Bunar) in Pakistan. Results revealed that 44/244 (18%) rodents amplified ITS-1 gene of Toxoplasma gondii through PCR. Parasite prevalence varied between the rodent species. Highest rate of infection was found in Rattus norvegicus followed by Rattus rattus and Mus musculus. For both rat species, Toxoplasma gondii infection significantly varies between the sampling districts. DNA sequencing and BLAST analysis confirmed the presence of Toxoplasma gondii in rodent blood samples. Phylogenetic analysis showed that Pakistani isolates were genetically diverse and clustered with the isolates that were reported from worldwide countries. Complete blood count analysis revealed that parasite infected rodents had disturbed lymphocyte, mean platelet volume, mean corpuscular volume (and mean corpuscular hemoglobin concentration. Markers of oxidative stress analysis revealed that infected rodent had elevated malondialdehyde levels in liver and kidney while disturb catalase concentrations in kidney and heart as compared to uninfected animals. In conclusion, we are reporting a relatively high prevalence of Toxoplasma gondii in Pakistani rodents. Infection leads to disturbed complete blood count and markers of oxidative stress in the vital organs. We recommend large scale studies in various geo-climatic regions of Pakistan to report the incidence and prevalence of this pathogen among the rodents in order to prevent their infections in local people as well as in livestock.
Enhanced homeostatic sleep response and decreased neurodegenerative proteins in cereblon knock-out mice
Authors: Jung Jun-Hyung , Kim Jinhong , Akber Uroos , Lee Na Young , Baek Jeong-won , Jung Jieun , Park Mincheol , Kang Jiseung , Jeon Seungje , Park Chul-Seung , Kim Tae 
Published: September 2024

AbstractEnergy homeostasis and sleep have a bidirectional relationship. Cereblon (CRBN) regulates energy levels by ubiquitinating the AMP-activated protein kinase(AMPK), an energy sensor. However, whether CRBN participates in sleep is unclear. Here, we examine sleep–wake patterns in Crbn+/+ and Crbn−/− mice during 24-h baseline, 6-h sleep deprivation (SD), and following 6-h recovery sleep (RS). At baseline, overall sleep patterns are similar between genotypes. However, SD decreases CRBN expression in Crbn+/+ mice and increases phospho-Tau, phospho-α-synuclein, DNAJA1 (DJ2), and DNAJB1 (DJ1) in both genotypes, with Crbn−/− mice showing a lesser extent of increase in p-Tau and p-α-synuclein and a higher level of heat shock protein 70 (HSP70), DJ2, and DJ1. During RS, Crbn−/− mice show increased slow-wave activity in the low-delta range (0.5–2.5 Hz), suggesting higher homeostatic sleep propensity associated with AMPK hyperactivation. By illuminating the role of CRBN in regulating sleep–wake behaviors through AMPK, we suggest CRBN as a potential therapeutic target for managing sleep disorders and preventing neurodegeneration.
Mildly explosive eruptions at Martian low-shield volcanoes
Authors: Pieterek Bartosz , Jones Thomas J. 
Published: September 2024

AbstractOngoing acquisition of Martian surface imagery constantly provides new opportunities to reveal previously undiscovered small-scale volcanic landforms, yielding critical insights into volcanic processes, and challenging existing inferences. Here, using the most recent, high-resolution topographical data, we mapped the accumulation of pyroclastic deposits occurring along the margins of several volcanic vents. They share morphological similarities with terrestrial volcanic deposits attributed to low-intensity lava fountaining occurring during mild explosive activity. Our identified, explosive volcanic deposits are associated with late Amazonian volcanic activity in Tharsis. The identification of these very recent (<100 Ma) deposits across the entire Tharsis volcanic province needs reconciling with our current view of the evolution of explosive volcanism on Mars. We contend that these small volume landforms, produced by mildly explosive volcanic activity, need to be considered in models surrounding planet-scale magmatic evolution and atmospheric volatile budgets.
Accounting for existing tenure and rights over marine and freshwater systems
Authors: Tholan Brittany , Basurto Xavier , Cohen Philippa J. , Franz Nicole , Himes-Cornell Amber , Govan Hugh , Fakoya Kafayat , Akintola Shehu L. , Aceves-Bueno Eréndira 
Published: September 2024

AbstractGlobal commitments to conservation and sustainable development increasingly demand sensitivity to the rights and territories of Indigenous peoples and local communities. However, existing tenure systems are often overlooked by global actors and their initiatives. Using key informant surveys, literature, and established databases, we describe 62 distinct tenure systems (or place-based, governance relationships between people and coasts) across 24 countries. In all systems, people held rights to access and use aquatic resources to support healthy diets, livelihoods, and culture. The three collective-choice rights (i.e., management, exclusion, transferability) were present in 29% of systems – suggesting conditions sufficient for “self-governance”. People gained or held rights due to their residency (in 63% of systems); through historical use (52%), permits (35%), and/or kinship (29%). Our synthesis provides an opportunity for policy and action to recognize these systems of tenure, and to stimulate further actions that illuminate and recognize the rights of communities toward their sovereignty.