bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation with cognitive functioning
Authors: Broeders Tommy A.A. , Bhogal Alex A. , Morsinkhof Lisan M. , Schoonheim Menno M. , Röder Christian H. , Edens Mirte , Klomp Dennis W.J. , Wijnen Jannie P. , Vinkers Christiaan H. 
Published: February 2021

ABSTRACTPatients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but knowledge on its role in deep gray matter regions is limited and previous studies have yielded heterogeneous results. The aim was to evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction and post-processing techniques. A 7 tesla MRI scanner combined with a unique lipid suppression coil and subject specific water signal suppression pulses were used to acquire high-resolution magnetic resonance spectroscopic imaging data. Anatomical scans were used to perform tissue fraction correction and registration to a standard brain for group comparison in specifically delineated brain regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. Average glutamate levels across deep gray matter structures (i.e. caudate, pallidum, putamen, and thalamus) in patients with a psychotic disorder (n=16, 4 females) were lower compared to healthy controls (n=23, 7 females). Stratified analyses showed lower glutamate levels in the caudate and putamen but not in the pallidum or thalamus. Average glutamate levels across deep gray matter structures were positively correlated with cognition, particularly to psychomotor speed. We find reduced glutamate levels across deep brain structures such as the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Our results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in patients with psychotic disorders.
Neurofilament light protein as a blood biomarker for Huntington’s disease in children
Authors: Byrne Lauren M , Schultz Jordan L , Rodrigues Filipe B , van der Plas Ellen , Langbehn Douglas , Nopoulos Peg , Wild Edward J 
Published: February 2021

AbstractJuvenile-onset Huntington’s disease (JoHD) is a rare, particularly devastating form of Huntington’s Disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD. We report that plasma NfL is elevated in JoHD and premanifest HD mutation-carrying children. Quantifying plasma NfL may improve clinical diagnosis and therapeutic trial design in the pediatric population.
Living with relatives offsets the harm caused by pathogens in natural populations
Authors: Bensch Hanna M. , O’Connor Emily , Cornwallis Charlie K. 
Published: February 2021

AbstractLiving with relatives can be highly beneficial, enhancing reproduction and survival. However, high relatedness can increase susceptibility to pathogens, a phenomenon known as the ‘monoculture effect’. Here we examine if the benefits of living with relatives offsets the harm caused by pathogens, and if this depends if species typically live with kin. Using comparative meta-analysis across plants, animals and bacteria (nspecies= 56), we show that high within-group relatedness increases mortality when pathogens are present. Contrastingly, mortality decreased with relatedness when pathogens were rare, particularly in species that live with kin. Variation in pathogen abundances was lower across groups of relatives, but rates of mortality were more unpredictable. The effects of within-group relatedness were only evident when pathogens were manipulated, suggesting that the harm caused by pathogens is masked by the benefits of living with relatives. These results highlight the importance of kin selection for understanding disease spread in natural populations.
CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal
Authors: Crozier Lisa , Foy Reece , Mouery Brandon L. , Whitaker Robert H. , Corno Andrea , Spanos Christos , Ly Tony , Cook Jeanette Gowen , Saurin Adrian T. 
Published: February 2021

AbstractCDK4/6 inhibitors arrest the cell cycle in G1-phase. They are approved to treat breast cancer and are also undergoing clinical trials against a range of other tumour types. To facilitate these efforts, it is important to understand why a cytostatic arrest in G1 causes long-lasting effects on tumour growth. Here we demonstrate that a prolonged G1-arrest following CDK4/6 inhibition downregulates replisome components and impairs origin licencing. This causes a failure in DNA replication after release from that arrest, resulting in a p53-dependent withdrawal from the cell cycle. If p53 is absent, then cells bypass the G2-checkpoint and undergo a catastrophic mitosis resulting in excessive DNA damage. These data therefore link CDK4/6 inhibition to genotoxic stress; a phenotype that is shared by most other broad-spectrum anti-cancer drugs. This provides a rationale to predict responsive tumour types and effective combination therapies, as demonstrated by the fact that CDK4/6 inhibition induces sensitivity to chemotherapeutics that also cause replication stress.
Plant pathogens convergently evolved to counteract redundant nodes of an NLR immune receptor network
Authors: Derevnina Lida , Contreras Mauricio P. , Adachi Hiroaki , Upson Jessica , Cruces Angel Vergara , Xie Rongrong , Sklenar Jan , Menke Frank L.H. , Mugford Sam T. , MacLean Dan , Ma Wenbo , Hogenhout Saskia , Goverse Aska , Maqbool Abbas , Wu Chih-Hang , Kamoun Sophien 
Published: February 2021

ABSTRACTIn plants, NLR (nucleotide-binding domain and leucine-rich repeat-containing) proteins can form receptor networks to confer hypersensitive cell death and innate immunity. One class of NLRs, known as NRCs (NLR required for cell death), are central nodes in a complex network that protects against multiple pathogens and comprises up to half of the NLRome of solanaceous plants. Given the prevalence of this NLR network, we hypothesized that pathogens convergently evolved to secrete effectors that target NRC activities. To test this, we screened a library of 167 bacterial, oomycete, nematode and aphid effectors for their capacity to suppress the cell death response triggered by the NRC-dependent disease resistance proteins Prf and Rpi-blb2. Among five of the identified suppressors, one cyst nematode protein and one oomycete protein suppress the activity of autoimmune mutants of NRC2 and NRC3, but not NRC4, indicating that they specifically counteract a subset of NRC proteins independently of their sensor NLR partners. Whereas the cyst nematode effector SPRYSEC15 binds the nucleotide-binding domain of NRC2 and NRC3, the oomycete effector AVRcap1b suppresses the response of these NRCs via the membrane trafficking-associated protein NbTOL9a (Target of Myb 1-like protein 9a). We conclude that plant pathogens have evolved to counteract central nodes of the NRC immune receptor network through different mechanisms. Coevolution with pathogen effectors may have driven NRC diversification into functionally redundant nodes in a massively expanded NLR network.
High-throughput selection of microalgae based on biomass accumulation rates in production environments using PicoShell Particles
Authors: van Zee Mark , de Rutte Joseph , Rumyan Rose , Williamson Cayden , Burnes Trevor , Radakovits Randor , Eugenio Andrew Sonico , Badih Sara , Lee Dong-Hyun , Archang Maani , Di Carlo Dino 
Published: February 2021

AbstractProduction of high-energy lipids by microalgae may provide a sustainable, renewable energy source that can help tackle climate change. However, microalgae engineered to produce more lipids usually grow slowly, leading to reduced overall yields. Unfortunately, tools that enable the selection of cells based on growth while maintaining high biomass production, such as well-plates, water-in-oil droplet emulsions, and nanowell arrays do not provide production-relevant environments that cells experience in scaled-up cultures (e.g. bioreactors or outdoor cultivation farms). As a result, strains that are developed in the lab often do not exhibit the same beneficial phenotypic behavior when transferred to industrial production. Here we introduce PicoShells, picoliter-scale porous hydrogel compartments, that can enable >100,000 individual cells to be compartmentalized, cultured in production-relevant environments, and selected based on growth and biomass accumulation traits using standard flow cytometers. PicoShells consist of a hollow inner cavity where cells are encapsulated, and a porous outer shell that allows for continuous solution exchange with the external environment so that nutrients, cell-communication factors, and cytotoxic cellular byproducts can transport freely in and out of the inner cavity. PicoShells can also be placed directly into shaking flasks, bioreactors, or other production-relevant environments. We experimentally demonstrate thatChlorellasp. andSaccharomyces cerevisiaegrow to significantly larger colony sizes in PicoShells than in water-in-oil droplet emulsions (P < 0.05). We have also demonstrated that PicoShells containing faster biomass accumulatingChlorellaclonal colonies can be selected using a fluorescence-activated cell sorter and re-grown. Using the PicoShell process, we select aChlorellapopulation that accumulates biomass 8% faster than does an un-selected population after a single selection cycle.
Two transcriptionally distinct pathways drive female development in a reptile with both genetic and temperature dependent sex determination
Authors: Whiteley Sarah L. , Holleley Clare E. , Wagner Susan , Blackburn James , Deveson Ira W. , Graves Jennifer A. Marshall , Georges Arthur 
Published: February 2021

AbstractHow temperature determines sex remains unknown. A recent hypothesis proposes that conserved cellular mechanisms (calcium and redox; ‘CaRe’ status) sense temperature and identify genes and regulatory pathways likely to be involved in driving sexual development. We take advantage of the unique sex determining system of the model organism,Pogona vitticeps, to assess predictions of this hypothesis.P. vitticepshas ZZ male: ZW female sex chromosomes whose influence can be overridden in genetic males by high temperatures, causing male-to-female sex reversal. We compare a developmental transcriptome series of ZWf females and temperature sex reversed ZZf females. We demonstrate that early developmental cascades differ dramatically between genetically driven and thermally driven females, later converging to produce a common outcome (ovaries). We show that genes proposed as regulators of thermosensitive sex determination play a role in temperature sex reversal. Our study greatly advances the search for the mechanisms by which temperature determines sex.Author SummaryIn many reptiles and fish, environment can determine, or influence, the sex of developing embryos. How this happens at a molecular level that has eluded resolution for half a century of intensive research. We studied the bearded dragon, a lizard that has sex chromosomes (ZZ male and ZW female), but in which that temperature can override ZZ sex chromosomes to cause male to female sex reversal. This provides an unparalleled opportunity to disentangle, in the same species, the biochemical pathways required to make a female by these two different routes. We sequenced the transcriptomes of gonads from developing ZZ reversed and normal ZW dragon embryos and discovered that different sets of genes are active in ovary development driven by genotype or temperature. Females whose sex was initiated by temperature showed a transcriptional profile consistent with the recently-proposed Calcium-Redox hypotheses of cellular temperature sensing. These findings are an important for understanding how the environment influences the development of sex, and more generally how the environment can epigenetically modify the action of genes.
Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2
Authors: Dwivedy Abhisek , Mariadasse Richard , Ahmad Mohammed , Chakraborty Sayan , Kar Deepsikha , Tiwari Satish , Majumdar Tanmay , Jeyakanthan Jeyaraman , Biswal Bichitra K. 
Published: February 2021

AbstractApart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of the NiRAN domain. Using in silico tools, we predict that the NiRAN domain assumes a kinase or phosphotransferase like fold and binds nucleoside triphosphates at its proposed active site. Additionally, using molecular docking we have predicted the binding of three widely used kinase inhibitors and five well characterized anti-microbial compounds at the NiRAN domain active site along with their drug-likeliness as well as DFT properties. For the first time ever, using basic biochemical tools, this study shows the presence of a kinase like activity exhibited by the SARS-CoV-2 RdRp. Interestingly, the proposed kinase inhibitors and a few of the predicted nucleotidyl transferase inhibitors significantly inhibited the aforementioned enzymatic activity. In line with the current global COVID-19 pandemic urgency and the emergence of newer strains with significantly higher infectivity, this study provides a new anti-SARS-CoV-2 drug target and potential lead compounds for drug repurposing against SARS-CoV-2.
Polar and non-polar fractions of deep fried edible oils induce differential cytotoxicity and hemolysis
Authors: Sneha P. , Paul Yemeema , Venugopal Mithula , Narayanankutty Arunaksharan 
Published: February 2021

AbstractEdible oils are the essential part of diet, however, deep frying process induce oxidative changes in these oils, making them unsuitable for consumption. Deep frying generates various noxious polar and non-polar aldehydes and carbonyls, which may be polar or non-polar in nature. The present study thus evaluated the cytotoxic and hemolytic effects of polar and non-polar fractions of different deep fried edible oils. There observed a significantly elevated level of lipid peroxidation products in the polar fraction of deep fried sunflower (FSO-P) and rice bran oils (FRO-P). The treatment with these fractions induced cytotoxicity in cultured colon epithelial cells, with a higher intensity in FSO-P and FRO-P. Further, an increased TBARS level and catalase activity in RBCs treated with FSO-P and FRO-P led to hemolysis. In comparison, the fried coconut oil (FCO) fractions were less toxic and hemolytic; in addition, the non-polar fraction was more toxic, compared to FCO-P fraction.
‘Nepotistic journals’: a survey of biomedical journals
Authors: Scanff Alexandre , Naudet Florian , Cristea Ioana , Moher David , Bishop Dorothy V M , Locher Clara 
Published: February 2021

AbstractContextConvergent analyses in different disciplines support the use of the Percentage of Papers by the Most Prolific author (PPMP) as a red flag to identify journals that can be suspected of questionable editorial practices. We examined whether this index, complemented by the Gini index, could be useful for identifying cases of potential editorial bias, using a large sample of biomedical journals.MethodsWe extracted metadata for all biomedical journals referenced in the National Library of Medicine, with any attributed Broad Subject Terms, and at least 50 authored (i.e. by at least one author) articles between 2015 and 2019, identifying the most prolific author (i.e. the person who signed the most papers in each particular journal). We calculated the PPMP and the 2015-2019 Gini index for the distribution of articles across authors. When the relevant information was reported, we also computed the median publication lag (time between submission and acceptance) for articles authored by any of the most prolific authors and that for articles not authored by prolific authors. For outlier journals, defined as a PPMP or Gini index above the 95th percentile of their respective distributions, a random sample of 100 journals was selected and described in relation to status on the editorial board for the most prolific author.Results5 468 journals that published 4 986 335 papers between 2015 and 2019 were analysed. The PPMP 95thpercentile was 10.6% (median 2.9%). The Gini index 95thpercentile was 0.355 (median 0.183). Correlation between the two indices was 0.35 (95CI 0.33 to 0.37). Information on publication lag was available for 2 743 journals. We found that 277 journals (10.2%) had a median time lag to publication for articles by the most prolific author(s) that was shorter than 3 weeks, versus 51 (1.9%) journals with articles not authored by prolific author(s). Among the random sample of outlier journals, 98 provided information about their editorial board. Among these 98, the most prolific author was part of the editorial board in 60 cases (61%), among whom 25 (26% of the 98) were editors-in-chief.DiscussionIn most journals publications are distributed across a large number of authors. Our results reveal a subset of journals where a few authors, often members of the editorial board, were responsible for a disproportionate number of publications. The papers by these authors were more likely to be accepted for publication within 3 weeks of their submission. To enhance trust in their practices, journals need to be transparent about their editorial and peer review practices.
Knowledge and Awareness of coronavirus disease 2019 (COVID-19) among Chinese dental students——a comparison study
Authors: Deng Chengdan , Ma Huangshui , Shou Yuke , Zhao Yuxuan , Li Yang , Shi Bing 
Published: February 2021

AbstractBackgroudThis study aimed to measure the knowledge and awareness of COVID-19 among Chinese dental students during the global outbreak recently.MethodA descriptive cross-sectional study was performed among dental students and nonmedical college students in China. All the participants were required to anonymously answer a reliable online questionnaire, which covered 3 different fields of COVID-19. Average scores of dental students (D group), including junior (JD group) and senior dental students (SD group), and nonmedical college students (N group) were compared respectively. Chi-square test and independent sample T test were taken for statistical analysis with SPSS.12.ResultsTotally 497 questionnaires were collected, including 224 from dental students and 273 from non-medical students. The overall average score was 57±19.2. The average scores of dental students were 64.5±18. The D group had significantly higher scores on the total score, section scores, and 20 questions respectively than with the N group. No significant differences were found on 5 questions. Compared with the N group, the SD group won on all three sections while JD group failed to win on the diagnose section.ConclusionAlthough the dental student showed good awareness regarding the clinical aspects of COVID-19 than non-medical students, there are still some weakness in the part of treatment and prevention, which need to be strengthened for better prepare during work. Besides, the low accuracy rate of lower grade dental students is also worth noting.
The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis
Authors: Haley Emma , Matmusaev Mederbek , Hossain Imtiyaz N. , Davin Sean , Martin Tammy M. , Ermann Joerg 
Published: February 2021

AbstractBackgroundOverexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated.MethodsWe compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA.FindingsMale B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight.ConclusionsSystemic IL-23 overexpression results in spondyloarthritis-like disease in B10.RIII mice. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests organ-specific genetic control mechanisms of IL-23 driven inflammation. Discrepancies regarding the phenotype of IL-23 induced disease in different labs and the sexual dimorphism observed in this study warrant further exploration.