bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations in Martian Lithospheric Strength Based on Gravity/Topography Analysis
Authors: Ding Min , Lin Jian , Gu Chen , Huang Qinghua , Zuber Maria T. 
Published: November 2019

AbstractWe applied localized gravity/topography admittance and correlation analysis, as well as the Markov chain Monte Carlo method, to invert for loading and flexural parameters of 21 subregions on Mars with five distinct tectonic types. The loading styles of the five tectonic types are distinct: The surface and subsurface loading in the polar and plain regions can be assumed to be largely uncorrelated, in contrast to the correlated loading associated with the volcanic montes and Valles Marineris. For the impact basins, we consider the initial topographic depression and mantle plug before postimpact surface loading. Our analyses yield four main results: (1) The inverted effective lithospheric thickness (Te) is highly dependent on assumptions of loading type. (2) There is a trend of increasing Te from the Noachian southern highlands (20–60 km) to the Hesperian northern lowlands (>90 km) and from the Hesperian Elysium Mons (<55 km) to the Hesperian/Amazonian Olympus Mons (>105 km). These Te estimates are consistent with the thermal states at the time of loading, corresponding to a global secular cooling history with decreasing heat flux. (3) Our analyses suggest high‐density basaltic surface loading at the volcanic montes and Isidis basin, in contrast to the low‐density sedimentary surface loading at the Utopia and Argyre basins. (4) We find some degree of correlation between the surface and subsurface loading for the northern polar cap and the northern plains, likely due to earlier, larger polar deposits and ancient buried features, respectively.
High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels
Authors: Chang Jane Pei-Chen , Su Kuan-Pin , Mondelli Valeria , Satyanarayanan Senthil Kumaran , Yang Hui-Ting , Chiang Yi-Ju , Chen Hui-Ting , Pariante Carmine M. 
Published: November 2019

AbstractNo studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6–18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.
Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome
Authors: Morin-Parent Florence , Champigny Camille , Lacroix Angelina , Corbin François , Lepage Jean-François 
Published: November 2019

AbstractFragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient γ-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.
Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy
Authors: Pretzsch Charlotte M , Voinescu Bogdan , Lythgoe David , Horder Jamie , Mendez Maria Andreina , Wichers Robert , Ajram Laura , Ivin Glynis , Heasman Martin , Edden Richard A. E. , Williams Steven , Murphy Declan G. M. , Daly Eileen , McAlonan Gráinne M. 
Published: November 2019

AbstractAutism spectrum disorder (ASD) is a high cost neurodevelopmental condition; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies – including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown. Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites – markers of the brain’s primary excitatory and inhibitory system - in both the ‘typical’ and autistic brain. Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design. We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the ‘shift’ in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group. Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.
Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases
Authors: Mundo Lucia , Ambrosio Maria Raffaella , Raimondi Francesco , Del Porro Leonardo , Guazzo Raffaella , Mancini Virginia , Granai Massimo , Jim Rocca Bruno , Lopez Cristina , Bens Susanne , Onyango Noel , Nyagol Joshua , Abinya Nicholas , Navari Mohsen , Ndede Isaac , Patel Kirkita , Paolo Piccaluga Pier , Bob Roshanak , de Santi Maria Margherita , Russell Robert B. , Lazzi Stefano , Siebert Reiner , Stein Harald , Leoncini Lorenzo 
Published: November 2019

AbstractMYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.
Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background
Authors: Rojas Elizabeta A. , Corchete Luis A. , Mateos María Victoria , García-Sanz Ramón , Misiewicz-Krzeminska Irena , Gutiérrez Norma C. 
Published: November 2019

AbstractPrimary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.
Airway epithelial regeneration requires autophagy and glucose metabolism
Authors: Li Kuan , Li Minmin , Li Wenli , Yu Hongzhi , Sun Xin , Zhang Qiuyang , Li Yu , Li Xue , Li Yue , Abel E. Dale , Wu Qi , Chen Huaiyong 
Published: November 2019

AbstractEfficient repair of injured epithelium by airway progenitor cells could prevent acute inflammation from progressing into chronic phase in lung. Here, we used small molecules, genetic loss-of-function, organoid cultures, and in vivo lung-injury models to show that autophagy is essential for maintaining the pool of airway stem-like vClub cells by promoting their proliferation during ovalbumin-induced acute inflammation. Mechanistically, impaired autophagy disrupted glucose uptake in vClub progenitor cells, and either reduced accessibility to glucose or partial inhibition of glycolysis promoted the proliferative capacity of vClub progenitor cells and their daughter Club cells. However, glucose deprivation or glycolysis blockade abrogated the proliferative capacity of airway vClub cells and Club cells but promoted ciliated and goblet cell differentiation. Deficiency of glucose transporter-1 suppressed the proliferative capacity of airway progenitor cells after ovalbumin challenge. These findings suggested that autophagy and glucose metabolism are essential for the maintenance of airway epithelium at steady state and during allergic inflammation.
Upregulation of IGF2R evades lysosomal dysfunction-induced apoptosis of cervical cancer cells via transport of cathepsins
Authors: Takeda Takashi , Komatsu Masayuki , Chiwaki Fumiko , Komatsuzaki Rie , Nakamura Kanako , Tsuji Kosuke , Kobayashi Yusuke , Tominaga Eiichiro , Ono Masaya , Banno Kouji , Aoki Daisuke , Sasaki Hiroki 
Published: November 2019

AbstractCervical cancer is the most common gynecological malignancy in the world; however, the survival rates of advanced-stage and recurrent cervical cancer patients remain poor. The multifaced protein insulin-like growth factor 2 receptor (IGF2R) has various ligands, represented as IGF-2 and mannose-6-phosphate (M6P)-tagged proteins. Regarding its antagonistic activity as an IGF1R signal, IGF2R is currently considered a tumor suppressor gene, whereas its significance as an M6P receptor is still unclear. Here, on the basis of transcriptome analysis of TCGA and GEO open datasets, we show that IGF2R is upregulated and correlated with poor prognosis in cervical cancer. Several experiments using cervical cancer cell lines revealed that IGF2R depletion induced apoptosis, decreased cell viability, and increased vulnerability to certain anticancer drug cisplatin. In contrast to its negligible impact in IGF1R signaling, loss of IGF2R disrupted the Golgi-to-lysosome transport of M6P-tagged cathepsins, resulting in decreased lysosomal activity, with their abnormal accumulation and dysfunction of both autophagy and mitophagy, which cause the accumulation of misfolded proteins and production of reactive oxygen species. Taken together, IGF2R has an oncogenic role through transportation of M6P-tagged cargo in cervical cancer and can be used as a predictive biomarker for prognostic classification.
Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors
Authors: Almeida Catarina F. , Sundararaj Srinivasan , Le Nours Jérôme , Praveena T. , Cao Benjamin , Burugupalli Satvika , Smith Dylan G. M. , Patel Onisha , Brigl Manfred , Pellicci Daniel G. , Williams Spencer J. , Uldrich Adam P. , Godfrey Dale I. , Rossjohn Jamie 
Published: November 2019

AbstractType I and type II natural killer T (NKT) cells are restricted to the lipid antigen-presenting molecule CD1d. While we have an understanding of the antigen reactivity and function of type I NKT cells, our knowledge of type II NKT cells in health and disease remains unclear. Here we describe a population of type II NKT cells that recognise and respond to the microbial antigen, α-glucuronosyl-diacylglycerol (α-GlcADAG) presented by CD1d, but not the prototypical type I NKT cell agonist, α-galactosylceramide. Surprisingly, the crystal structure of a type II NKT TCR-CD1d-α-GlcADAG complex reveals a CD1d F’-pocket-docking mode that contrasts sharply with the previously determined A’-roof positioning of a sulfatide-reactive type II NKT TCR. Our data also suggest that diverse type II NKT TCRs directed against distinct microbial or mammalian lipid antigens adopt multiple recognition strategies on CD1d, thereby maximising the potential for type II NKT cells to detect different lipid antigens.
Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy
Authors: Park Hongryeol , Yamamoto Hiroyuki , Mohn Lucas , Ambühl Lea , Kanai Kenichi , Schmidt Inga , Kim Kee-Pyo , Fraccaroli Alessia , Feil Silke , Junge Harald J. , Montanez Eloi , Berger Wolfgang , Adams Ralf H. 
Published: November 2019

AbstractFamilial exudative vitreoretinopathy (FEVR) is a human disease characterized by defective retinal angiogenesis and associated complications that can result in vision loss. Defective Wnt/β-catenin signaling is an established cause of FEVR, whereas other molecular alterations contributing to the disease remain insufficiently understood. Here, we show that integrin-linked kinase (ILK), a mediator of cell-matrix interactions, is indispensable for retinal angiogenesis. Inactivation of the murine Ilk gene in postnatal endothelial cells results in sprouting defects, reduced endothelial proliferation and disruption of the blood-retina barrier, resembling phenotypes seen in established mouse models of FEVR. Retinal vascularization defects are phenocopied by inducible inactivation of the gene for α-parvin (Parva), an interactor of ILK. Screening genomic DNA samples from exudative vitreoretinopathy patients identifies three distinct mutations in human ILK, which compromise the function of the gene product in vitro. Together, our data suggest that defective cell-matrix interactions are linked to Wnt signaling and FEVR.
Highly variable iron content modulates iceberg-ocean fertilisation and potential carbon export
Authors: Hopwood Mark J. , Carroll Dustin , Höfer Juan , Achterberg Eric P. , Meire Lorenz , Le Moigne Frédéric A. C. , Bach Lennart T. , Eich Charlotte , Sutherland David A. , González Humberto E. 
Published: November 2019

AbstractMarine phytoplankton growth at high latitudes is extensively limited by iron availability. Icebergs are a vector transporting the bioessential micronutrient iron into polar oceans. Therefore, increasing iceberg fluxes due to global warming have the potential to increase marine productivity and carbon export, creating a negative climate feedback. However, the magnitude of the iceberg iron flux, the subsequent fertilization effect and the resultant carbon export have not been quantified. Using a global analysis of iceberg samples, we reveal that iceberg iron concentrations vary over 6 orders of magnitude. Our results demonstrate that, whilst icebergs are the largest source of iron to the polar oceans, the heterogeneous iron distribution within ice moderates iron delivery to offshore waters and likely also affects the subsequent ocean iron enrichment. Future marine productivity may therefore be not only sensitive to increasing total iceberg fluxes, but also to changing iceberg properties, internal sediment distribution and melt dynamics.
Structural determinants of microtubule minus end preference in CAMSAP CKK domains
Authors: Atherton Joseph , Luo Yanzhang , Xiang Shengqi , Yang Chao , Rai Ankit , Jiang Kai , Stangier Marcel , Vemu Annapurna , Cook Alexander D. , Wang Su , Roll-Mecak Antonina , Steinmetz Michel O. , Akhmanova Anna , Baldus Marc , Moores Carolyn A. 
Published: November 2019

AbstractCAMSAP/Patronins regulate microtubule minus-end dynamics. Their end specificity is mediated by their CKK domains, which we proposed recognise specific tubulin conformations found at minus ends. To critically test this idea, we compared the human CAMSAP1 CKK domain (HsCKK) with a CKK domain from Naegleria gruberi (NgCKK), which lacks minus-end specificity. Here we report near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes, which show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit different footprints on microtubules. NMR experiments show that both HsCKK and NgCKK are remarkably rigid. However, whereas NgCKK binding does not alter the microtubule architecture, HsCKK remodels its microtubule interaction site and changes the underlying polymer structure because the tubulin lattice conformation is not optimal for its binding. Thus, in contrast to many MAPs, the HsCKK domain can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.
Towards the application of Tc toxins as a universal protein translocation system
Authors: Roderer Daniel , Schubert Evelyn , Sitsel Oleg , Raunser Stefan 
Published: November 2019

AbstractTc toxins are bacterial protein complexes that inject cytotoxic enzymes into target cells using a syringe-like mechanism. Tc toxins are composed of a membrane translocator and a cocoon that encapsulates a toxic enzyme. The toxic enzyme varies between Tc toxins from different species and is not conserved. Here, we investigate whether the toxic enzyme can be replaced by other small proteins of different origin and properties, namely Cdc42, herpes simplex virus ICP47, Arabidopsis thaliana iLOV, Escherichia coli DHFR, Ras-binding domain of CRAF kinase, and TEV protease. Using a combination of electron microscopy, X-ray crystallography and in vitro translocation assays, we demonstrate that it is possible to turn Tc toxins into customizable molecular syringes for delivering proteins of interest across membranes. We also infer the guidelines that protein cargos must obey in terms of size, charge, and fold in order to apply Tc toxins as a universal protein translocation system.
Combined orbital tomography study of multi-configurational molecular adsorbate systems
Authors: Kliuiev Pavel , Zamborlini Giovanni , Jugovac Matteo , Gurdal Yeliz , Arx Karin von , Waltar Kay , Schnidrig Stephan , Alberto Roger , Iannuzzi Marcella , Feyer Vitaliy , Hengsberger Matthias , Osterwalder Jürg , Castiglioni Luca 
Published: November 2019

AbstractMolecular reactivity is determined by the energy levels and spatial extent of the frontier orbitals. Orbital tomography based on angle-resolved photoelectron spectroscopy is an elegant method to study the electronic structure of organic adsorbates, however, it is conventionally restricted to systems with one single rotational domain. In this work, we extend orbital tomography to systems with multiple rotational domains. We characterise the hydrogen evolution catalyst Co-pyrphyrin on an Ag(110) substrate and compare it with the empty pyrphyrin ligand. In combination with low-energy electron diffraction and DFT simulations, we fully determine adsorption geometry and both energetics and spatial distributions of the valence electronic states. We find two states close to the Fermi level in Co-pyrphyrin with Co $$3d$$
3
d
character that are not present in the empty ligand. In addition, we identify several energetically nearly equivalent adsorption geometries that are important for the understanding of the electronic structure. The ability to disentangle and fully elucidate multi-configurational systems renders orbital tomography much more useful to study realistic catalytic systems.