bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy-induced senescence is regulated by p38α signaling
Authors: Slobodnyuk Konstantin , Radic Nevenka , Ivanova Saška , Llado Anna , Trempolec Natalia , Zorzano Antonio , Nebreda Angel R. 
Published: May 2019

AbstractApoptosis and senescence are two mutually exclusive cell fate programs that can be activated by stress. The factors that instruct cells to enter into senescence or apoptosis are not fully understood, but both programs can be regulated by the stress kinase p38α. Using an inducible system that specifically activates this pathway, we show that sustained p38α activation suffices to trigger massive autophagosome formation and to enhance the basal autophagic flux. This requires the concurrent effect of increased mitochondrial reactive oxygen species production and the phosphorylation of the ULK1 kinase on Ser-555 by p38α. Moreover, we demonstrate that macroautophagy induction by p38α signaling determines that cancer cells preferentially enter senescence instead of undergoing apoptosis. In agreement with these results, we present evidence that the induction of autophagy by p38α protects cancer cells from chemotherapy-induced apoptosis by promoting senescence. Our results identify a new mechanism of p38α-regulated basal autophagy that controls the fate of cancer cells in response to stress.
Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Authors: Lees John A. , Ferwerda Bart , Kremer Philip H. C. , Wheeler Nicole E. , Serón Mercedes Valls , Croucher Nicholas J. , Gladstone Rebecca A. , Bootsma Hester J. , Rots Nynke Y. , Wijmega-Monsuur Alienke J. , Sanders Elisabeth A. M. , Trzciński Krzysztof , Wyllie Anne L. , Zwinderman Aeilko H. , van den Berg Leonard H. , van Rheenen Wouter , Veldink Jan H. , Harboe Zitta B. , Lundbo Lene F. , de Groot Lisette C. P. G. M. , van Schoor Natasja M. , van der Velde Nathalie , Ängquist Lars H. , Sørensen Thorkild I. A. , Nohr Ellen A. , Mentzer Alexander J. , Mills Tara C. , Knight Julian C. , du Plessis Mignon , Nzenze Susan , Weiser Jeffrey N. , Parkhill Julian , Madhi Shabir , Benfield Thomas , von Gottberg Anne , van der Ende Arie , Brouwer Matthijs C. , Barrett Jeffrey C. , Bentley Stephen D. , van de Beek Diederik 
Published: May 2019

AbstractStreptococcus pneumoniaeis a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants inCCDC33associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness includingpspCandzmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
Evaluating cell lines as models for metastatic breast cancer through integrative analysis of genomic data
Authors: Liu Ke , Newbury Patrick A. , Glicksberg Benjamin S. , Zeng William Z. D. , Paithankar Shreya , Andrechek Eran R. , Chen Bin 
Published: May 2019

AbstractCell lines are widely-used models to study metastatic cancer although the extent to which they recapitulate the disease in patients remains unknown. The recent accumulation of genomic data provides an unprecedented opportunity to evaluate the utility of them for metastatic cancer research. Here, we reveal substantial genomic differences between breast cancer cell lines and metastatic breast cancer patient samples. We also identify cell lines that more closely resemble the different subtypes of metastatic breast cancer seen in the clinic and show that surprisingly, MDA-MB-231 cells bear little genomic similarities to basal-like metastatic breast cancer patient samples. Further comparison suggests that organoids more closely resemble the transcriptome of metastatic breast cancer samples compared to cell lines. Our work provides a guide for cell line selection in the context of breast cancer metastasis and highlights the potential of organoids in these studies.
Limited capacity of tree growth to mitigate the global greenhouse effect under predicted warming
Authors: Büntgen Ulf , Krusic Paul J. , Piermattei Alma , Coomes David A. , Esper Jan , Myglan Vladimir S. , Kirdyanov Alexander V. , Camarero J. Julio , Crivellaro Alan , Körner Christian 
Published: May 2019

AbstractIt is generally accepted that animal heartbeat and lifespan are often inversely correlated, however, the relationship between productivity and longevity has not yet been described for trees growing under industrial and pre-industrial climates. Using 1768 annually resolved and absolutely dated ring width measurement series from living and dead conifers that grew in undisturbed, high-elevation sites in the Spanish Pyrenees and the Russian Altai over the past 2000 years, we test the hypothesis of grow fast—die young. We find maximum tree ages are significantly correlated with slow juvenile growth rates. We conclude, the interdependence between higher stem productivity, faster tree turnover, and shorter carbon residence time, reduces the capacity of forest ecosystems to store carbon under a climate warming-induced stimulation of tree growth at policy-relevant timescales.
Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy
Authors: Dobaño Carlota , Sanz Hèctor , Sorgho Hermann , Dosoo David , Mpina Maximilian , Ubillos Itziar , Aguilar Ruth , Ford Tom , Díez-Padrisa Núria , Williams Nana Aba , Ayestaran Aintzane , Traore Ousmane , Nhabomba Augusto J. , Jairoce Chenjerai , Waitumbi John , Agnandji Selidji Todagbe , Kariuki Simon , Abdulla Salim , Aponte John J. , Mordmüller Benjamin , Asante Kwaku Poku , Owusu-Agyei Seth , Tinto Halidou , Campo Joseph J. , Moncunill Gemma , Gyan Ben , Valim Clarissa , Daubenberger Claudia 
Published: May 2019

AbstractRTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48–0.76]) and avidity to C-terminus (0.07 [0.05–0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.
Coordination corrected ab initio formation enthalpies
Authors: Friedrich Rico , Usanmaz Demet , Oses Corey , Supka Andrew , Fornari Marco , Buongiorno Nardelli Marco , Toher Cormac , Curtarolo Stefano 
Published: May 2019

AbstractThe correct calculation of formation enthalpy is one of the enablers of ab-initio computational materials design. For several classes of systems (e.g. oxides) standard density functional theory produces incorrect values. Here we propose the “coordination corrected enthalpies” method (CCE), based on the number of nearest neighbor cation–anion bonds, and also capable of correcting relative stability of polymorphs. CCE uses calculations employing the Perdew, Burke and Ernzerhof (PBE), local density approximation (LDA) and strongly constrained and appropriately normed (SCAN) exchange correlation functionals, in conjunction with a quasiharmonic Debye model to treat zero-point vibrational and thermal effects. The benchmark, performed on binary and ternary oxides (halides), shows very accurate room temperature results for all functionals, with the smallest mean absolute error of 27(24) meV/atom obtained with SCAN. The zero-point vibrational and thermal contributions to the formation enthalpies are small and with different signs—largely canceling each other.
Recovery of stem cell proliferation by low intensity vibration under simulated microgravity requires LINC complex
Authors: Touchstone H. , Bryd R. , Loisate S. , Thompson M. , Kim S. , Puranam K. , Senthilnathan A. N. , Pu X. , Beard R. , Rubin J. , Alwood J. , Oxford J. T. , Uzer G. 
Published: May 2019

AbstractMesenchymal stem cells (MSC) rely on their ability to integrate physical and spatial signals at load bearing sites to replace and renew musculoskeletal tissues. Designed to mimic unloading experienced during spaceflight, preclinical unloading and simulated microgravity models show that alteration of gravitational loading limits proliferative activity of stem cells. Emerging evidence indicates that this loss of proliferation may be linked to loss of cellular cytoskeleton and contractility. Low intensity vibration (LIV) is an exercise mimetic that promotes proliferation and differentiation of MSCs by enhancing cell structure. Here, we asked whether application of LIV could restore the reduced proliferative capacity seen in MSCs that are subjected to simulated microgravity. We found that simulated microgravity (sMG) decreased cell proliferation and simultaneously compromised cell structure. These changes included increased nuclear height, disorganized apical F-actin structure, reduced expression, and protein levels of nuclear lamina elements LaminA/C LaminB1 as well as linker of nucleoskeleton and cytoskeleton (LINC) complex elements Sun-2 and Nesprin-2. Application of LIV restored cell proliferation and nuclear proteins LaminA/C and Sun-2. An intact LINC function was required for LIV effect; disabling LINC functionality via co-depletion of Sun-1, and Sun-2 prevented rescue of cell proliferation by LIV. Our findings show that sMG alters nuclear structure and leads to decreased cell proliferation, but does not diminish LINC complex mediated mechanosensitivity, suggesting LIV as a potential candidate to combat sMG-induced proliferation loss.
Fractional quantum Hall effects in In0.75Ga0.25As bilayer electron systems observed as “Finger print”
Authors: Yamada Syoji , Fujimoto Akira , Hidaka Siro , Akabori Masashi , Imanaka Yasutaka , Takehana Kanji 
Published: May 2019

AbstractObservations of fractional quantum Hall (FQH) plateaus are reported in bilayer electron gas system in wide (>80 nm) In0.75Ga0.25As wells. Several q/p (p = 5, 3, and 2, q > 5) QH states are confirmed at high temperatures (~1.6 K) when the critical conditions including an electron density imbalance as well as a dynamical resistance behavior at the bilayer-monolayer transition are properly satisfied. The former leads to a quantum limit in either of the layers and the latter might bring a meta-stable nature into FQH phenomena. Such a behavior occurs as a probability process associating with impurities or defects in the wells, they inevitably reflect the local structural landscapes of each sample. This is verified by the new finding that the kinds of fractional plateaus (what set of fractional filling factors) appeared are different depending on the samples, that is, they are the “finger print” in each sample.
The involvement of autotaxin in renal interstitial fibrosis through regulation of fibroblast functions and induction of vascular leakage
Authors: Sakai Norihiko , Bain Gretchen , Furuichi Kengo , Iwata Yasunori , Nakamura Miki , Hara Akinori , Kitajima Shinji , Sagara Akihiro , Miyake Taito , Toyama Tadashi , Sato Koichi , Nakagawa Shiori , Shimizu Miho , Kaneko Shuichi , Wada Takashi 
Published: May 2019

AbstractThe accumulation of fibroblasts is a critical step in the development of fibrosis, and lysophosphatidic acid (LPA) promotes fibrosis by regulating multiple fibroblast functions. Autotaxin (ATX) is a key LPA-producing enzyme, and we hypothesized that ATX contributes to the development of renal interstitial fibrosis through LPA-mediated effects on fibroblast functions. In a mouse model of renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO), the levels of renal ATX protein and activity increased with the progression of fibrosis in ligated kidneys, despite concurrent reductions in renal ATX mRNA. UUO enhanced vascular permeability in the renal interstitium, and ATX protein localized to areas of vascular leak, suggesting that vascular leak allowed ATX to enter the renal interstitium. In vitro studies showed that ATX induces the migration and proliferation of renal fibroblasts and enhances the vascular permeability of endothelial monolayers. Finally, pharmacological inhibition of ATX partially attenuated renal interstitial fibrosis. These results suggest that during the development of renal fibrosis, ATX accumulates in the renal interstitium and drives fibroblast accumulation and promotes renal interstitial vascular leak, thereby partially contributing to the pathogenesis of renal interstitial fibrosis. Taken together, ATX inhibition may have the potential to be a novel therapeutic strategy to combat renal interstitial fibrosis.
Enhanced metastatic potential in the MB49 urothelial carcinoma model
Authors: Liu Yu-Ru , Yin Peng-Nien , Silvers Christopher R. , Lee Yi-Fen 
Published: May 2019

AbstractRecent data suggest that patients with a basal/stem-like bladder cancer (BC) subtype tend to have metastatic disease, but this is unconfirmed. Here we report the identification of murine MB49 cell line sub-clones with stem-like characteristics in culture. Subcutaneous implantation of S2 and S4 MB49 sub-clones into immunocompetent mice resulted in lung metastases in 50% and 80% of mice respectively, whereas none of the mice implanted with the parental cells developed metastasis. Gene profiling of cells cultured from S2 and S4 primary and metastatic tumors revealed that a panel of genes with basal/stem-like/EMT properties is amplified during metastatic progression. Among them, ITGB1, TWIST1 and KRT6B are consistently up-regulated in metastatic tumors of both MB49 sub-clones. To evaluate clinical relevance, we examined these genes in a human public dataset and found that ITGB1 and KRT6B expression in BC patient tumor samples are positively correlated with tumor grade. Likewise, the expression levels of these three genes are correlated with worse clinical outcomes. This MB49 BC metastatic pre-clinical model provides a unique opportunity to validate and recapitulate results discovered in patient studies and to pursue future mechanistic therapeutic interventions for BC metastasis.
Controlling parameters and characteristics of electrochemical biosensors for enhanced detection of 8-hydroxy-2′-deoxyguanosine
Authors: Faria Aline M. , Peixoto Elisa B. M. I. , Adamo Cristina B. , Flacker Alexander , Longo Elson , Mazon Talita 
Published: May 2019

AbstractThis work discusses the parameters and characteristics required on the development of a scalable and reliable electrochemical sensor board for detecting 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative stress biomarker for diabetic nephropathy, cancer and Parkinson’s disease. We used Printed Circuit Board (PCB) technology to make a precise, low-cost bare sensor board. ZnO nanorods (NRs) and ZnO NRs: reduced graphene oxide (RGO) composites were used as a pathway for antibody immobilization on the working electrode (WE). The parameters and characteristics of the WE were controlled for enhancing the quality of the electrochemical sensor board. Thickness of the gold and the presence of ZnO NRs or their composite on the WE have influence on charge transference process and reproducibility of the sensor board. The amount of the antibody, and its incubation period are crucial to avoid saturation of the sites during immobilization step and reduce the cost of the sensor. Our ZnO NRs-based electrochemical sensor board showed high sensitivity and selectivity to 8-OHdG with detection capacity in the range of 0.001–5.00 ng.mL−1. The successful application of our immunosensor to detect 8-OHdG in urine was evidenced.
Aquaporin 4 inhibition alters chemokine receptor expression and T cell trafficking
Authors: Nicosia Michael , Miyairi Satoshi , Beavers Ashley , Farr George W. , McGuirk Paul R. , Pelletier Marc F. , Valujskikh Anna 
Published: May 2019

AbstractAquaporins (AQPs) are water channels that mediate a variety of biological processes. However, their role in the immune system is poorly understood. We recently reported that AQP4 is expressed by naïve and memory T cells and that AQP4 blockade with a small molecule inhibitor prolongs murine heart allograft survival at least partially through diminishing T cell activation, proliferation and trafficking. The goal of this study was to determine how AQP4 function impacts T cells in the absence of antigen stimulation. AQP4 inhibition transiently reduced the number of circulating CD4+ and CD8+ T cells in naïve non-transplanted mice in the absence of systemic T cell depletion. Adoptive transfer studies demonstrated T cell intrinsic effect of AQP4 inhibition. AQP4 blockade altered T cell gene and protein expression of chemokine receptors S1PR1 and CCR7, and their master regulator KLF-2, and reduced chemotaxis toward S1P and CCL21. Consistent with the in vitro data, in vivo AQP4 inhibition reduced T lymphocyte numbers in the lymph nodes with simultaneous accumulation in the liver. Our findings indicate that blocking AQP4 reversibly alters T lymphocyte trafficking pattern. This information can be explored for the treatment of undesirable immune responses in transplant recipients or in patients with autoimmune diseases.
Development and validation of a novel panel of 16 STR markers for simultaneous diagnosis of β-thalassemia, aneuploidy screening, maternal cell contamination detection and fetal sample authenticity in PND and PGD/PGS cases
Authors: Sharifi Zohreh , Rahiminejad Faezeh , Joudaki Atefeh , Bandehi Ameneh Sarhadi , Farahzadi Hossein , Keshvar Yeganeh , Golnabi Fatemeh , Naderi Sanaz , Yazdani Rasaneh , Shafaat Mehdi , Ghadami Shirin , Abiri Maryam , Zeinali Sirous 
Published: May 2019

AbstractPrenatal diagnosis (PND) may be complicated with sample mix-up; maternal cell contamination, non-paternity and allele drop out at different stages of diagnosis. Aneuploidy screening if combined with PND for a given single gene disorder, can help to detect any common aneuploidy as well as aiding sample authenticity and other probable complications which may arise during such procedures. This study was carried out to evaluate the effectiveness of a novel panel of STR markers combined as a multiplex PCR kit (HapScreen™ kit) for the detection of β-thalassemia, aneuploidy screening, ruling in/out maternal cell contamination (MCC), and sample authenticity. The kit uses 7 STR markers linked to β-globin gene (HBB) as well as using 9 markers for quantitative analysis of chromosomes 21, 18, 13, X and Y. Selection of the markers was to do linkage analysis with β-globin gene, segregation analysis and to perform a preliminary aneuploidy screening of fetal samples respectively. These markers (linked to the β-globin gene) were tested on more than 2185 samples and showed high heterozygosity values (68.4–91.4%). From 2185 fetal cases we found 3 cases of non-paternity, 5 cases of MCC, one case of sample mix-up and one case of trisomy 21 which otherwise may have end up to misdiagnosis. This kit was also successfully used on 231 blastomeres for 29 cases of pre-implantation genetic diagnosis (PGD) and screening (PGS). The markers used for simultaneous analysis of haplotype segregation and aneuploidy screening proved to be very valuable to confirm results obtained from direct mutation detection methods (i.e. ARMS, MLPA and sequencing) and aneuploidy screening.
Segmental differences of cervical spinal cord motion: advancing from confounders to a diagnostic tool
Authors: Hupp M. , Vallotton K. , Brockmann C. , Huwyler S. , Rosner J. , Sutter R. , Klarhoefer M. , Freund P. , Farshad M. , Curt A. 
Published: May 2019

AbstractIncreased cranio-caudal spinal cord motion is associated with clinical impairment in degenerative cervical myelopathy. However, whether spinal cord motion holds potential as a neuroimaging biomarker requires further validation. Different confounders (i.e. subject characteristics, methodological problems such as phase drift, etc.) on spinal cord motion readouts have to be considered. Twenty-two healthy subjects underwent phase contrast MRI, a subset of subjects (N = 9) had repeated scans. Parameters of interest included amplitude of velocity signal, maximum cranial respectively maximum caudal velocity, displacement (=area under curve of the velocity signal). The cervical spinal cord showed pulse synchronic oscillatory motions with significant differences in all readouts across cervical segments, with a maximum at C5. The Inter-rater reliability was excellent for all readouts. The test-retest reliability was excellent for all parameters at C2 to C6, but not for maximum cranial velocity at C6 and all readouts at C7. Spinal cord motion was correlated with spinal canal size, heart rate and body size. This is the first study to propose a standardized MRI measurement of spinal cord motion for further clinical implementation based on satisfactory phase drift correction and excellent reliability. Understanding the influence of confounders (e.g. structural conditions of the spine) is essential for introducing cord motion into the diagnostic work up.
Food knowledge depends upon the integrity of both sensory and functional properties: a VBM, TBSS and DTI tractography study
Authors: Vignando Miriam , Aiello Marilena , Rinaldi Adriana , Cattarruzza Tatiana , Mazzon Giulia , Manganotti Paolo , Eleopra Roberto , Rumiati Raffaella I. 
Published: May 2019

AbstractFood constitutes a fuel of life for human beings. It is therefore of chief importance that their recognition system readily identifies the most relevant properties of food by drawing on semantic memory. One of the most relevant properties to be considered is the level of processing impressed by humans on food. We hypothesized that recognition of raw food capitalizes on sensory properties and that of transformed food on functional properties, consistently with the hypothesis of a sensory-functional organization of semantic knowledge. To test this hypothesis, patients with Alzheimer’s disease, frontotemporal dementia, primary progressive aphasia, and healthy controls performed lexical-semantic tasks with food (raw and transformed) and non-food (living and nonliving) stimuli. Correlations between task performance and local grey matter concentration (VBM) and white matter fractional anisotropy (TBSS) led to two main findings. First, recognition of raw food and living things implicated occipital cortices, typically involved in processing sensory information and, second, recognition of processed food and nonliving things implicated the middle temporal gyrus and surrounding white matter tracts, regions that have been associated with functional properties. In conclusion, the present study confirms and extends the hypothesis of a sensory and a functional organization of semantic knowledge.