bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease
Authors: Szabo Peter A. , Levitin Hanna Mendes , Miron Michelle , Snyder Mark E. , Senda Takashi , Yuan Jinzhou , Cheng Yim Ling , Bush Erin C. , Dogra Pranay , Thapa Puspa , Farber Donna L. , Sims Peter A. 
Published: October 2019

AbstractHuman T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.
A fast and sensitive room-temperature graphene nanomechanical bolometer
Authors: Blaikie Andrew , Miller David , Alemán Benjamín J. 
Published: October 2019

AbstractBolometers are a powerful means of detecting light. Emerging applications demand that bolometers work at room temperature, while maintaining high speed and sensitivity, properties which are inherently limited by the heat capacity of the detector. To this end, graphene has generated interest, because it has the lowest mass per unit area of any material, while also possessing extreme thermal stability and an unmatched spectral absorbance. Yet, due to its weakly temperature-dependent electrical resistivity, graphene has failed to challenge the state-of-the-art at room temperature. Here, in a departure from conventional bolometry, we use a graphene nanoelectromechanical system to detect light via resonant sensing. In our approach, absorbed light heats and thermally tensions a suspended graphene resonator, thereby shifting its resonant frequency. Using the resonant frequency as a readout for photodetection, we achieve a room-temperature noise-equivalent power (2 pW Hz−1/2) and bandwidth (from 10 kHz up to 1.3 MHz), challenging the state-of-the-art.
De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes
Authors: Watkins W. Scott , Hernandez E. Javier , Wesolowski Sergiusz , Bisgrove Brent W. , Sunderland Ryan T. , Lin Edwin , Lemmon Gordon , Demarest Bradley L. , Miller Thomas A. , Bernstein Daniel , Brueckner Martina , Chung Wendy K. , Gelb Bruce D. , Goldmuntz Elizabeth , Newburger Jane W. , Seidman Christine E. , Shen Yufeng , Yost H. Joseph , Yandell Mark , Tristani-Firouzi Martin 
Published: October 2019

AbstractThe genetic architecture of sporadic congenital heart disease (CHD) is characterized by enrichment in damaging de novo variants in chromatin-modifying genes. To test the hypothesis that gene pathways contributing to de novo forms of CHD are distinct from those for recessive forms, we analyze 2391 whole-exome trios from the Pediatric Cardiac Genomics Consortium. We deploy a permutation-based gene-burden analysis to identify damaging recessive and compound heterozygous genotypes and disease genes, controlling for confounding effects, such as background mutation rate and ancestry. Cilia-related genes are significantly enriched for damaging rare recessive genotypes, but comparatively depleted for de novo variants. The opposite trend is observed for chromatin-modifying genes. Other cardiac developmental gene classes have less stratification by mode of inheritance than cilia and chromatin-modifying gene classes. Our analyses reveal dominant and recessive CHD are associated with distinct gene functions, with cilia-related genes providing a reservoir of rare segregating variation leading to CHD.
Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo
Authors: Akieda Yuki , Ogamino Shohei , Furuie Hironobu , Ishitani Shizuka , Akiyoshi Ryutaro , Nogami Jumpei , Masuda Takamasa , Shimizu Nobuyuki , Ohkawa Yasuyuki , Ishitani Tohru 
Published: October 2019

AbstractMorphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
Mice with hyper-long telomeres show less metabolic aging and longer lifespans
Authors: Muñoz-Lorente Miguel A. , Cano-Martin Alba C. , Blasco Maria A. 
Published: October 2019

AbstractShort telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.
Epigenetic modifiers DNMT3A and BCOR are recurrently mutated in CYLD cutaneous syndrome
Authors: Davies Helen R. , Hodgson Kirsty , Schwalbe Edward , Coxhead Jonathan , Sinclair Naomi , Zou Xueqing , Cockell Simon , Husain Akhtar , Nik-Zainal Serena , Rajan Neil 
Published: October 2019

AbstractPatients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. Here, we comprehensively profile the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families and discover recurrent mutations in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumors suggest that isoform-specific DNMT3A2 mutations are associated with dysregulated methylation. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumors. These findings contribute to existing paradigms of cutaneous tumorigenesis and metastasis.
Quadruple bonding between iron and boron in the BFe(CO)3− complex
Authors: Chi Chaoxian , Wang Jia-Qi , Hu Han-Shi , Zhang Yang-Yang , Li Wan-Lu , Meng Luyan , Luo Mingbiao , Zhou Mingfei , Li Jun 
Published: October 2019

AbstractWhile main group elements have four valence orbitals accessible for bonding, quadruple bonding to main group elements is extremely rare. Here we report that main group element boron is able to form quadruple bonding interactions with iron in the BFe(CO)3- anion complex, which has been revealed by quantum chemical investigation and identified by mass-selected infrared photodissociation spectroscopy in the gas phase. The complex is characterized to have a B-Fe(CO)3− structure of C3v symmetry and features a B-Fe bond distance that is much shorter than that expected for a triple bond. Various chemical bonding analyses indicate that the complex involves unprecedented B≣Fe quadruple bonding interactions. Besides the common one electron-sharing σ bond and two Fe→B dative π bonds, there is an additional weak B→Fe dative σ bonding interaction. This finding of the new quadruple bonding indicates that there might exist a wide range of boron-metal complexes that contain such high multiplicity of chemical bonds.
Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts
Authors: St. John-Williams Lisa , Mahmoudiandehkordi Siamak , Arnold Matthias , Massaro Tyler , Blach Colette , Kastenmüller Gabi , Louie Gregory , Kueider-Paisley Alexandra , Han Xianlin , Baillie Rebecca , Motsinger-Reif Alison A. , Rotroff Daniel , Nho Kwangsik , Saykin Andrew J. , Risacher Shannon L. , Koal Therese , Moseley M. Arthur , Tenenbaum Jessica D. , Thompson J. Will , Kaddurah-Daouk Rima ,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium
Published: October 2019

AbstractAlzheimer’s disease (AD) is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related factors. There is a growing body of evidence that metabolic defects may contribute to this complex disease. To interrogate the relationship between system level metabolites and disease susceptibility and progression, the AD Metabolomics Consortium (ADMC) in partnership with AD Neuroimaging Initiative (ADNI) is creating a comprehensive biochemical database for patients in the ADNI1 cohort. We used the Biocrates Bile Acids platform to evaluate the association of metabolic levels with disease risk and progression. We detail the quantitative metabolomics data generated on the baseline samples from ADNI1 and ADNIGO/2 (370 cognitively normal, 887 mild cognitive impairment, and 305 AD). Similar to our previous reports on ADNI1, we present the tools for data quality control and initial analysis. This data descriptor represents the third in a series of comprehensive metabolomics datasets from the ADMC on the ADNI.
Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading
Authors: Sobue Yasumori , Takahashi Nobunori , Ohashi Yoshifumi , Suzuki Mochihito , Nishiume Tsuyoshi , Kobayakawa Tomonori , Terabe Kenya , Knudson Warren , Knudson Cheryl , Ishiguro Naoki , Kojima Toshihisa 
Published: October 2019

AbstractCD44 fragmentation is enhanced in chondrocytes of osteoarthritis (OA) patients. We hypothesized that mechanical stress-induced enhancement of CD44-intracellular domain (CD44-ICD) production plays an important role in the de-differentiation of chondrocytes and OA. This study aimed to assess the relationship between CD44-ICD and chondrocyte gene expression. Monolayer cultured primary bovine articular chondrocytes (BACs) were subjected to cyclic tensile strain (CTS) loading. ADAM10 inhibitor (GI254023X) and γ-secretase inhibitor (DAPT) were used to inhibit CD44 cleavage. In overexpression experiments, BACs were electroporated with a plasmid encoding CD44-ICD. CTS loading increased the expression of ADAM10 and subsequent CD44 cleavage, while decreasing the expression of SOX9, aggrecan, and type 2 collagen (COL2). Overexpression of CD44-ICD also resulted in decreased expression of these chondrocyte genes. Both GI254023X and DAPT reduced the production of CD44-ICD upon CTS loading, and significantly rescued the reduction of SOX9 expression by CTS loading. Chemical inhibition of CD44-ICD production also rescued aggrecan and COL2 expression following CTS loading. Our findings suggest that CD44-ICD is closely associated with the de-differentiation of chondrocytes. Excessive mechanical stress loading promoted the de-differentiation of BACs by enhancing CD44 cleavage and CD44-ICD production. Suppression of CD44 cleavage has potential as a novel treatment strategy for OA.
Controls on Dissolved Organic Carbon Bioreactivity in River Systems
Authors: Soares Ana R. A. , Lapierre Jean-François , Selvam Balathandayuthabani P. , Lindström Göran , Berggren Martin 
Published: October 2019

AbstractInland waters transport, transform and retain significant amounts of dissolved organic carbon (DOC) that may be biologically reactive (bioreactive) and thus potentially degraded into atmospheric CO2. Despite its global importance, relatively little is known about environmental controls on bioreactivity of DOC as it moves through river systems with varying water residence time (WRT). Here we determined the influence of WRT and landscape properties on DOC bioreactivity in 15 Swedish catchments spanning a large geographical and environmental gradient. We found that the short-term bioreactive pools (0–6 d of decay experiments) were linked to high aquatic primary productivity that, in turn, was stimulated by phosphorus loading from forested, agricultural and urban areas. Unexpectedly, the percentage of long-term bioreactive DOC (determined in 1-year experiments) increased with WRT, possibly due to photo-transformation of recalcitrant DOC from terrestrial sources into long-term bioreactive DOC with relatively lower aromaticity. Thus, despite overall decreases in DOC during water transit through the inland water continuum, DOC becomes relatively more bioreactive on a long time-scale. This increase in DOC bioreactivity with increasing WRT along the freshwater continuum has previously been overlooked. Further studies are needed to explain the processes and mechanisms behind this pattern on a molecular level.
Downhill seed dispersal by temperate mammals: a potential threat to plant escape from global warming
Authors: Naoe Shoji , Tayasu Ichiro , Sakai Yoichiro , Masaki Takashi , Kobayashi Kazuki , Nakajima Akiko , Sato Yoshikazu , Yamazaki Koji , Kiyokawa Hiroki , Koike Shinsuke 
Published: October 2019

AbstractVertical seed dispersal, i.e. seed dispersal towards a higher or lower altitude, is considered a critical process for plant escape from climate change. However, studies exploring vertical seed dispersal are scarce, and thus, its direction, frequency, and mechanisms are little known. In the temperate zone, evaluating vertical seed dispersal of animal-dispersed plants fruiting in autumn and/or winter is essential considering the dominance of such plants in temperate forests. We hypothesized that their seeds are dispersed towards lower altitudes because of the downhill movement of frugivorous animals following the autumn-to-winter phenology of their food plants which proceeds from the mountain tops to the foot in the temperate zone. We evaluated the vertical seed dispersal of the autumn-fruiting wild kiwi,Actinidia arguta, which is dispersed by temperate mammals. We collected dispersed seeds from mammal faeces in the Kanto Mountains of central Japan and estimated the distance of vertical seed dispersal using the oxygen isotope ratios of the dispersed seeds. We found the intensive downhill seed dispersal of wild kiwi by all seed dispersers, except the raccoon dog (bear: mean −393.1 m; marten: −245.3 m; macaque: −98.5 m; and raccoon dog: +4.5 m). Mammals with larger home ranges dispersed seeds longer towards the foot of the mountains. Furthermore, we found that seeds produced at higher altitudes were dispersed a greater distance towards the foot of the mountains. Altitudinal gradients in autumn-to-winter plant phenology and other mountain characteristics, i.e. larger surface areas and more attractive human crops at lower altitudes compared to higher altitudes, were considered drivers of downhill seed dispersal via animal movement. Strong downhill seed dispersal by mammals suggests that populations of autumn-to-winter fruiting plants dispersed by animals may not be able to sufficiently escape from current global warming in the temperate zone.
Systematic study of resonant transmission effects in visible band using variable depth gratings
Authors: Ushkov Andrei A. , Shcherbakov Alexey A. , Verrier Isabelle , Kampfe Thomas , Jourlin Yves 
Published: October 2019

AbstractThe article focuses on depth-dependent visible band transmission effects in a symmetrical “insulator-metal-insulator” diffraction system based on a variable depth grating. These effects were studied both experimentally and theoretically in TM and TE polarizations. In particular, the existence of an optimized grating depth for plasmon-mediated resonant transmission was confirmed experimentally, and differences in TE and TM transmission behavior are discussed. We utilize a simple and flexible fabrication approach for rapid synthesis of apodized structures with adiabatically varying depth based on a beat pattern of two interferential lithography exposures. The present study can be useful in the fields of transmission-based optical security elements and biosensors.
Comparative evaluation of affibody- and antibody fragments-based CAIX imaging probes in mice bearing renal cell carcinoma xenografts
Authors: Garousi Javad , Huizing Fokko J. , Vorobyeva Anzhelika , Mitran Bogdan , Andersson Ken G. , Leitao Charles Dahlsson , Frejd Fredrik Y. , Löfblom John , Bussink Johan , Orlova Anna , Heskamp Sandra , Tolmachev Vladimir 
Published: October 2019

AbstractCarbonic anhydrase IX (CAIX) is a cancer-associated molecular target for several classes of therapeutics. CAIX is overexpressed in a large fraction of renal cell carcinomas (RCC). Radionuclide molecular imaging of CAIX-expression might offer a non-invasive methodology for stratification of patients with disseminated RCC for CAIX-targeting therapeutics. Radiolabeled monoclonal antibodies and their fragments are actively investigated for imaging of CAIX expression. Promising alternatives are small non-immunoglobulin scaffold proteins, such as affibody molecules. A CAIX-targeting affibody ZCAIX:2 was re-designed with the aim to decrease off-target interactions and increase imaging contrast. The new tracer, DOTA-HE3-ZCAIX:2, was labeled with 111In and characterized in vitro. Tumor-targeting properties of [111In]In-DOTA-HE3-ZCAIX:2 were compared head-to-head with properties of the parental variant, [99mTc]Tc(CO)3-HE3-ZCAIX:2, and the most promising antibody fragment-based tracer, [111In]In-DTPA-G250(Fab’)2, in the same batch of nude mice bearing CAIX-expressing RCC xenografts. Compared to the 99mTc-labeled parental variant, [111In]In-DOTA-HE3-ZCAIX:2 provides significantly higher tumor-to-lung, tumor-to-bone and tumor-to-liver ratios, which is essential for imaging of CAIX expression in the major metastatic sites of RCC. [111In]In-DOTA-HE3-ZCAIX:2 offers significantly higher tumor-to-organ ratios compared with [111In]In-G250(Fab’)2. In conclusion, [111In]In-DOTA-HE3-ZCAIX:2 can be considered as a highly promising tracer for imaging of CAIX expression in RCC metastases based on our results and literature data.
Modeling Living Cells Within Microfluidic Systems Using Cellular Automata Models
Authors: Ballesteros Hernando Julia , Ramos Gómez Milagros , Díaz Lantada Andrés 
Published: October 2019

AbstractSeveral computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.
Vitamin D Supplementation for Premenstrual Syndrome-Related inflammation and antioxidant markers in students with vitamin D deficient: a randomized clinical trial
Authors: Heidari Hajar , Amani Reza , Feizi Awat , Askari Gholamreza , Kohan Shahnaz , Tavasoli Parastoo 
Published: October 2019

AbstractPremenstrual syndrome (PMS) is a common disorder in the reproductive age that negatively significant impacts on women’s quality of life. This randomized clinical trial study was undertaken to investigate the effect of vitamin D supplementation on inflammatory and antioxidant markers in 44 vitamin D deficient (25(OH)D < 20 ng/mL) students with PMS. Participants received either 50,000 IU vitamin D3 or a placebo pearl fortnightly for 4 months. At the baseline and in the last 2 months of intervention, participants were asked to complete the PMS Daily Symptoms Rating form along with taking the pearls and their blood samples were collected to assess serum levels of 25(OH)D3, Interleukin10 and 12 (IL-10, IL-12) and total antioxidant capacity (TAC). In vitamin D group, serum levels of IL-10 and IL-12 significantly decreased while TAC significantly increased post-intervention. There were significant differences regarding serum IL-12 and TAC levels between the two groups. Mean score of the total PMS symptoms showed significant improvement in 25(OH)D. Vitamin D supplementation seems to be an effective strategy to improve inflammation and antioxidant markers in vitamin D deficient women with PMS. This clinical trial was registered at Iranian Registry of Clinical Trials on 20/06/2018 (IRCT20180525039822N1).