bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia
Authors: Lin Xia-Hui , Qiu Bai-Quan , Ma Min , Zhang Rui , Hsu Shu-Jung , Liu Hua-Hua , Chen Jun , Gao Dong-Mei , Cui Jie-Feng , Ren Zheng-Gang , Chen Rong-Xin 
Published: July 2020

AbstractTransarterial embolization/transarterial chemoembolization (TAE/TACE) is the acceptable palliative treatment for hepatocellular carcinoma (HCC), mainly through ischemic necrosis induced by arterial embolization. However, how HCC cells survive under such ischemic hypoxic condition remains unclear, which can be exploited to potentiate TAE/TACE treatment. We hypothesized that targeting mitophagy can increase HCC cell apoptosis during hypoxia. HCC cells were subjected to hypoxia and then mitophagy was quantified. The role of dynamin-related protein 1 (DRP1) in hypoxia-induced HCC mitophagy was determined. Moreover, the synergistic effect of hypoxia and DRP1 inhibitor on HCC apoptosis was assessed in vitro and in vivo. Clinical association between DRP1 expression and outcome for HCC patients was validated. HCC cells that survived hypoxia showed significantly increased DRP1-mediated mitochondrial fission and mitophagy compared with cells in normoxia. Hypoxia induced mitophagy in surviving HCC cells by enhancing DRP1 expression and its translocation into the mitochondria and excessive mitochondrial fission into fragments. Blocking the DRP1 heightened the possibility of hypoxic cytotoxicity to HCC cells due to impaired mitophagy and increased the mitochondrial apoptosis, which involved decreased in mitochondrial membrane potential and mitochondrial release of apoptosis-inducing factor and cytochrome c. Additionally, DRP1 inhibitor Mdivi-1 suppressed the in vivo growth of hypoxia-exposed HCC cells. High expression of DRP1 was significantly associated with shorter survival in HCC patients. In conclusion, our results demonstrate that blocking DRP1-mediated mitochondrial fission and mitophagy increases the incidence of mitochondrial apoptosis of HCC cells during hypoxia, suggesting the new approach of targeting mitophagy to potentiate TAE/TACE.
Mutations in sphingolipid metabolism genes are associated with ADHD
Authors: Henriquez-Henriquez Marcela , Acosta Maria T. , Martinez Ariel F. , Vélez Jorge I. , Lopera Francisco , Pineda David , Palacio Juan D. , Quiroga Teresa , Worgall Tilla S. , Deckelbaum Richard J. , Mastronardi Claudio , Molina Brooke S. G. ,   the MTA Cooperative Group, Vitiello Benedetto , Severe Joanne B. , Jensen Peter S. , Arnold L. Eugene , Hoagwood Kimberly , Richters John , Vereen Donald R. , Hinshaw Stephen P. , Elliott Glen R. , Wells Karen C. , Epstein Jeffery N. , Murray Desiree W. , Conners C. Keith , March John , Swanson James , Wigal Timothy , Cantwell Dennis P. , Abikoff Howard B. , Hechtman Lily , Greenhill Laurence L. , Newcorn Jeffrey H. , Molina Brooke S. G. , Hoza Betsy , Pelham William E. , Gibbons Robert D. , Marcus Sue , Hur Kwan , Kraemer Helena C. , Hanley Thomas , Stern Karen , Arcos-Burgos Mauricio , Muenke Maximilian 
Published: July 2020

AbstractAttention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75–80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC,CERS6,SMPD1,SMPDL3B,CERS2,FADS3,ELOVL5, andCERK). Successful local replication for associations with variants inGALC,SMPD1, andCERS6was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increasedGALCexpression in the cerebellum.
Tauopathy in the young autistic brain: novel biomarker and therapeutic target
Authors: Grigg Iris , Ivashko-Pachima Yanina , Hait Tom Aharon , Korenková Vlasta , Touloumi Olga , Lagoudaki Roza , Van Dijck Anke , Marusic Zlatko , Anicic Mirna , Vukovic Jurica , Kooy R. Frank , Grigoriadis Nikolaos , Gozes Illana 
Published: July 2020

AbstractGiven our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer’s disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c.2244Adup/p.His559Glnfs*3 allowed exploration of tauopathy, reflecting on a general unexplored mechanism. The tested subject exhibited autism, fine motor delays, severe intellectual disability and seizures. The patient died after multiple organ failure following liver transplantation. To compare to other ADNP syndrome mutations, immortalized lymphoblastoid cell lines from three different patients (including ADNP p.Arg216*, p.Lys408Valfs*31, and p.Tyr719* heterozygous dominant mutations) and a control were subjected to RNA-seq. Immunohistochemistry, high-throughput gene expression profiles in numerous postmortem tissues followed. Comparisons to a control brain and to extensive datasets were used. Live cell imaging investigated Tau-microtubule interaction, protecting against tauopathy. Extensive child brain tauopathy paralleled by multiple gene expression changes was discovered. Tauopathy was explained by direct mutation effects on Tau-microtubule interaction and correction by the ADNP active snippet NAP. Significant pathway changes (empirical P value < 0.05) included over 100 genes encompassing neuroactive ligand–receptor and cytokine–cytokine receptor interaction, MAPK and calcium signaling, axon guidance and Wnt signaling pathways. Changes were also seen in steroid biosynthesis genes, suggesting sex differences. Selecting the most affected genes by the ADNP mutations for gene expression analysis, in multiple postmortem tissues, identified Tau (MAPT)-gene-related expression changes compared with extensive normal gene expression (RNA-seq) databases. ADNP showed relatively reduced expression in the ADNP syndrome cerebellum, which was also observed for 25 additional genes (representing >50% of the tested genes), including NLGN1, NLGN2, PAX6, SMARCA4, and SNAP25, converging on nervous system development and tauopathy. NAP provided protection against mutated ADNP disrupted Tau-microtubule association. In conclusion, tauopathy may explain brain-imaging findings in ADNP syndrome children and may provide a new direction for the development of tauopathy protecting drug candidates like NAP in ASD/ID.
In vivo human brain expression of histone deacetylases in bipolar disorder
Authors: Tseng Chieh-En J. , Gilbert Tonya M. , Catanese Mary C. , Hightower Baileigh G. , Peters Amy T. , Parmar Anjali J. , Kim Minhae , Wang Changning , Roffman Joshua L. , Brown Hannah E. , Perlis Roy H. , Zürcher Nicole R. , Hooker Jacob M. 
Published: July 2020

AbstractThe etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [11C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance – positron emission tomography (MR-PET) scan with [11C]Martinostat. Lower [11C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [11C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [11C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [11C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.
Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice
Authors: Wang Jun , Sun Bin-Lu , Xiang Yang , Tian Ding-Yuan , Zhu Chi , Li Wei-Wei , Liu Yu-Hui , Bu Xian-Le , Shen Lin-Lin , Jin Wang-Sheng , Wang Zhen , Zeng Gui-Hua , Xu Wei , Chen Li-Yong , Chen Xiao-Wei , Hu Zhian , Zhu Zhi-Ming , Song Weihong , Zhou Hua-Dong , Yu Jin-Tai , Wang Yan-Jiang 
Published: July 2020

AbstractAlzheimer’s disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.
Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position
Authors: Jones Christopher M. , Radhakrishna Ganesh , Aitken Katharine , Bridgewater John , Corrie Pippa , Eatock Martin , Goody Rebecca , Ghaneh Paula , Good James , Grose Derek , Holyoake Daniel , Hunt Arabella , Jamieson Nigel B. , Palmer Daniel H. , Soonawalla Zahir , Valle Juan W. , Hawkins Maria A. , Mukherjee Somnath 
Published: July 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk–benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk–benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.
Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes
Authors: Di Fede Elisabetta , Massa Valentina , Augello Bartolomeo , Squeo Gabriella , Scarano Emanuela , Perri Anna Maria , Fischetto Rita , Causio Francesco Andrea , Zampino Giuseppe , Piccione Maria , Curridori Elena , Mazza Tommaso , Castellana Stefano , Larizza Lidia , Ghelma Filippo , Colombo Elisa Adele , Gandini Maria Chiara , Castori Marco , Merla Giuseppe , Milani Donatella , Gervasini Cristina 
Published: July 2020

AbstractLysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as “writer” of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann–Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein–Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions.
A global dataset of surface water and groundwater salinity measurements from 1980–2019
Authors: Thorslund Josefin , van Vliet Michelle T. H. 
Published: July 2020

AbstractSalinization of freshwater resources is a growing water quality challenge, which may negatively impact both sectoral water-use and food security, as well as biodiversity and ecosystem services. Although monitoring of salinity is relatively common compared to many other water quality parameters, no compilation and harmonisation of available datasets for both surface and groundwater components have been made yet at the global scale. Here, we present a new global salinity database, compiled from electrical conductivity (EC) monitoring data of both surface water (rivers, lakes/reservoirs) and groundwater locations over the period 1980–2019. The data were assembled from a range of sources, including local to global salinity databases, governmental organizations, river basin management commissions and water development boards. Our resulting database comprises more than 16.3 million measurements from 45,103 surface water locations and 208,550 groundwater locations around the world. This database could provide new opportunities for meta-analyses of salinity levels of water resources, as well as for addressing data and model-driven questions related to historic and future salinization patterns and impacts.
GlobalFungi, a global database of fungal occurrences from high-throughput-sequencing metabarcoding studies
Authors: Větrovský Tomáš , Morais Daniel , Kohout Petr , Lepinay Clémentine , Algora Camelia , Awokunle Hollá Sandra , Bahnmann Barbara Doreen , Bílohnědá Květa , Brabcová Vendula , D’Alò Federica , Human Zander Rainier , Jomura Mayuko , Kolařík Miroslav , Kvasničková Jana , Lladó Salvador , López-Mondéjar Rubén , Martinović Tijana , Mašínová Tereza , Meszárošová Lenka , Michalčíková Lenka , Michalová Tereza , Mundra Sunil , Navrátilová Diana , Odriozola Iñaki , Piché-Choquette Sarah , Štursová Martina , Švec Karel , Tláskal Vojtěch , Urbanová Michaela , Vlk Lukáš , Voříšková Jana , Žifčáková Lucia , Baldrian Petr 
Published: July 2020

AbstractFungi are key players in vital ecosystem services, spanning carbon cycling, decomposition, symbiotic associations with cultivated and wild plants and pathogenicity. The high importance of fungi in ecosystem processes contrasts with the incompleteness of our understanding of the patterns of fungal biogeography and the environmental factors that drive those patterns. To reduce this gap of knowledge, we collected and validated data published on the composition of soil fungal communities in terrestrial environments including soil and plant-associated habitats and made them publicly accessible through a user interface athttps://globalfungi.com. The GlobalFungi database contains over 600 million observations of fungal sequences across > 17 000 samples with geographical locations and additional metadata contained in 178 original studies with millions of unique nucleotide sequences (sequence variants) of the fungal internal transcribed spacers (ITS) 1 and 2 representing fungal species and genera. The study represents the most comprehensive atlas of global fungal distribution, and it is framed in such a way that third-party data addition is possible.
Japan prefectural emission accounts and socioeconomic data 2007 to 2015
Authors: Long Yin , Yoshida Yoshikuni , Zhang Haoran , Zheng Heran , Shan Yuli , Guan Dabo 
Published: July 2020

AbstractIn the wake of the Fukushima nuclear disaster, Japan largely moved away from nuclear power generation and turned back towards an energy sector dominated by fossil fuels. As a result, the pace towards reaching emission reduction targets has largely slowed down. This situation indicates that higher emissions will continue to be generated if there is no appropriate and efficient measurement implemented to bridge the energy demand gap. To contribute adequate mitigation policies, a detailed inventory of both CO2 emissions and socioeconomic factors, both at the national and regional level, should be issued. Thereby, this work contributes to a time-series emission with a record of 47 prefectures in Japan as well as their associated socioeconomic features. The compiled emission inventory is based on three major fossil fuels and 26 sectors with careful emission allocations for regional electricity generation. This dataset is uniformly formatted and can be expected to provide vital information to set regional reduction allowances and sectoral reduction priorities.
Evaluation of various commodities for the development of the yellow mealworm, Tenebrio molitor
Authors: Rumbos Christos I. , Karapanagiotidis Ioannis T. , Mente Eleni , Psofakis Pier , Athanassiou Christos G. 
Published: July 2020

AbstractWe evaluated the suitability of forty-four commodities (i.e., cereal flours and meals, non-flour, cereal commodities, legumes and various commodities of vegetative and animal origin) as oviposition and feeding substrates for the yellow mealworm,Tenebrio molitor. ΤenT. molitoradults were introduced in plastic vials containing 30 g of each commodity. At the end of the 1 week period, all adults were removed, and mortality was determined; then the vials were further incubated for additional 9 weeks. After this time, the vials were opened, and the larvae of each vial were separated from the feeding substrate, counted and weighed as a group. The efficiency of ingested food conversion was calculated for each substrate. Finally, proximate composition was calculated to determine the nutrient components of the feeding substrates tested and theT. molitorlarvae that fed on various selected substrates. In general, adult reproduction was clearly favoured by most amylaceous substrates tested, which was in contrast to the tested legumes on which fewer offspring were produced. Similar effects were observed for larval development. Feeding on selected substrates exerted an impact on the nutrient composition ofT. molitorlarvae, with a high protein content of the substrate usually resulting in a high protein content of the larvae.
Near-chromosome level genome assembly of the fruit pest Drosophila suzukii using long-read sequencing
Authors: Paris Mathilde , Boyer Roxane , Jaenichen Rita , Wolf Jochen , Karageorgi Marianthi , Green Jack , Cagnon Mathilde , Parinello Hugues , Estoup Arnaud , Gautier Mathieu , Gompel Nicolas , Prud’homme Benjamin 
Published: July 2020

AbstractOver the past decade, the spotted wing Drosophila, Drosophila suzukii, has invaded Europe and America and has become a major agricultural pest in these areas, thereby prompting intense research activities to better understand its biology. Two draft genome assemblies already exist for this species but contain pervasive assembly errors and are highly fragmented, which limits their values. Our purpose here was to improve the assembly of theD. suzukiigenome and to annotate it in a way that facilitates comparisons withD. melanogaster. For this, we generated PacBio long-read sequencing data and assembled a novel, high-qualityD. suzukiigenome assembly. It is one of the largestDrosophilagenomes, notably because of the expansion of its repeatome. We found that despite 16 rounds of full-sib crossings theD. suzukiistrain that we sequenced has maintained high levels of polymorphism in some regions of its genome. As a consequence, the quality of the assembly of these regions was reduced. We explored possible origins of this high residual diversity, including the presence of structural variants and a possible heterogeneous admixture pattern of North American and Asian ancestry. Overall, our assembly and annotation constitute a high-quality genomic resource that can be used for both high-throughput sequencing approaches, as well as manipulative genetic technologies to studyD. suzukii.