bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel analysis of tri-molecular biosynthesis with cell identity and function in single cells
Authors: Kimmey Samuel C. , Borges Luciene , Baskar Reema , Bendall Sean C. 
Published: March 2019

AbstractCellular products derived from the activity of DNA, RNA, and protein synthesis collectively control cell identity and function. Yet there is little information on how these three biosynthesis activities are coordinated during transient and sparse cellular processes, such as activation and differentiation. Here, we describe Simultaneous Overview of tri-Molecule Biosynthesis (SOM3B), a molecular labeling and simultaneous detection strategy to quantify DNA, RNA, and protein synthesis in individual cells. Comprehensive interrogation of biosynthesis activities during transient cell states, such as progression through cell cycle or cellular differentiation, is achieved by partnering SOM3B with parallel quantification of select biomolecules with conjugated antibody reagents. Here, we investigate differential de novo DNA, RNA, and protein synthesis dynamics in transformed human cell lines, primary activated human immune cells, and across the healthy human hematopoietic continuum, all at a single-cell resolution.
Nuclear lamina integrity is required for proper spatial organization of chromatin in Drosophila
Authors: Ulianov Sergey V. , Doronin Semen A. , Khrameeva Ekaterina E. , Kos Pavel I. , Luzhin Artem V. , Starikov Sergei S. , Galitsyna Aleksandra A. , Nenasheva Valentina V. , Ilyin Artem A. , Flyamer Ilya M. , Mikhaleva Elena A. , Logacheva Mariya D. , Gelfand Mikhail S. , Chertovich Alexander V. , Gavrilov Alexey A. , Razin Sergey V. , Shevelyov Yuri Y. 
Published: March 2019

AbstractHow the nuclear lamina (NL) impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to chromatin compaction and repositioning from the nuclear envelope. This increases the chromatin density in a fraction of topologically-associating domains (TADs) enriched in active chromatin and enhances interactions between active and inactive chromatin. Importantly, upon NL disruption the NL-associated TADs become more acetylated at histone H3 and less compact, while background transcription is derepressed. Two-colour FISH confirms that a TAD becomes less compact following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
Mycobacterium tuberculosis Rv3463 induces mycobactericidal activity in macrophages by enhancing phagolysosomal fusion and exhibits therapeutic potential
Authors: Park Hye-Soo , Back Yong Woo , Shin Ki-Won , Bae Hyun Shik , Lee Kang-In , Choi Han-Gyu , Choi Seunga , Lee Hwang-Ho , Choi Chul Hee , Park Jeong-Kyu , Kim Hwa-Jung 
Published: March 2019

AbstractMacrophages are responsible for innate and adaptive immune response activation necessary for eliminating infections. Optimal activation of macrophages to phagocytize Mycobacterium tuberculosis is critical in anti-mycobacterial defense. Here, we identified a novel Rv3463 hypothetical protein that induces macrophage activation in Mtb culture filtrate. Recombinant Rv3463 activated mouse bone marrow-derived macrophages to induce the expression of surface molecules and secrete pro-inflammatory cytokines via the TLR2 and TLR4 pathways. Mitogen activated protein kinase, phospatidylinositol-4,5-bisphosphate 3-kinases, and the NF-κB signaling pathways are involved in Rv3463-mediated macrophage activation. Furthermore, Rv3463 induced bactericidal effects in Mtb-infected macrophages through phagosome maturation and phagolysosomal fusion enhanced by phospatidylinositol-4,5-bisphosphate 3-kinases and Ca2+ signaling pathways and exhibited therapeutic effects in a short-term Mtb-infection mouse model. Overexpression of Rv3463 in M. smegmatis caused rapid clearance of bacteria in macrophages and mice. Our study suggests that Rv3463 is a promising target for the development of post-exposure tuberculosis vaccines or adjunct immune-therapy.
Apparent absence of Batrachochytrium salamandrivorans in wild urodeles in the United Kingdom
Authors: Cunningham Andrew A. , Smith Freya , McKinley Trevelyan J. , Perkins Matthew W. , Fitzpatrick Liam D. , Wright Owen N. , Lawson Becki 
Published: March 2019

AbstractWhether an infectious disease threat to wildlife arises from pathogen introduction or the increased incidence of an already-present agent informs mitigation policy and actions. The prior absence of a pathogen can be difficult to establish, particularly in free-living wildlife. Subsequent to the epidemic emergence of the fungus, Batrachochytrium salamandrivorans (Bsal), in mainland Europe in 2010 and prior to its detection in captive amphibians in the United Kingdom (UK), we tested archived skin swabs using a Bsal-specific qPCR. These samples had been collected in 2011 from 2409 wild newts from ponds across the UK. All swabs were negative for Bsal. Bayesian hierarchical modelling suggests that Bsal was absent from, or present at very low levels in, these ponds at the time of sampling. Additionally, surveillance of newt mortality incidents, 2013–2017, failed to detect Bsal. As this pathogen has been shown to be widespread in British captive amphibian collections, there is an urgent need to raise awareness of the importance of effective biosecurity measures, especially amongst people with captive amphibians, to help minimise the risk of Bsal spreading to the wild. Continued and heightened wild amphibian disease surveillance is a priority to provide an early warning system for potential incursion events.
Magnetism in iridate heterostructures leveraged by structural distortions
Authors: Meyers D. , Cao Yue , Fabbris G. , Robinson Neil J. , Hao Lin , Frederick C. , Traynor N. , Yang J. , Lin Jiaqi , Upton M. H. , Casa D. , Kim Jong-Woo , Gog T. , Karapetrova E. , Choi Yongseong , Haskel D. , Ryan P. J. , Horak Lukas , Liu X. , Liu Jian , Dean M. P. M. 
Published: March 2019

AbstractFundamental control of magnetic coupling through heterostructure morphology is a prerequisite for rational engineering of magnetic ground states. We report the tuning of magnetic interactions in superlattices composed of single and bilayers of SrIrO3 inter-spaced with SrTiO3 in analogy to the Ruddlesden-Popper series iridates. Magnetic scattering shows predominately c-axis antiferromagnetic orientation of the magnetic moments for the bilayer, as in Sr3Ir2O7. However, the magnetic excitation gap, measured by resonant inelastic x-ray scattering, is quite different between the two structures, evidencing a significant change in the stability of the competing magnetic phases. In contrast, the single layer iridate hosts a more bulk-like gap. We find these changes are driven by bending of the c-axis Ir-O-Ir bond, which is much weaker in the single layer, and subsequent local environment changes, evidenced through x-ray diffraction and magnetic excitation modeling. Our findings demonstrate how large changes in the magnetic interactions can be tailored and probed in spin-orbit coupled heterostructures by engineering subtle structural modulations.
Pivotal role of inter-organ aspartate metabolism for treatment of mitochondrial aspartate-glutamate carrier 2 (citrin) deficiency, based on the mouse model
Authors: Saheki Takeyori , Moriyama Mitsuaki , Kuroda Eishi , Funahashi Aki , Yasuda Izumi , Setogawa Yoshiko , Gao Qinghua , Ushikai Miharu , Furuie Sumie , Yamamura Ken-ichi , Takano Katsura , Nakamura Yoichi , Eto Kazuhiro , Kadowaki Takashi , Sinasac David S. , Furukawa Tatsuhiko , Horiuchi Masahisa , Tai Yen How 
Published: March 2019

AbstractPrevious studies using citrin/mitochondrial glycerol-3-phosphate (G3P) dehydrogenase (mGPD) double-knockout mice have demonstrated that increased dietary protein reduces the extent of carbohydrate-induced hyperammonemia observed in these mice. This study aimed to further elucidate the mechanisms of this effect. Specific amino acids were initially found to decrease hepatic G3P, or increase aspartate or citrulline levels, in mGPD-knockout mice administered ethanol. Unexpectedly, oral glycine increased ammonia in addition to lowering G3P and increasing citrulline. Subsequently, simultaneous glycine-plus-sucrose (Gly + Suc) administration led to a more severe hyperammonemic state in double-KO mice compared to sucrose alone. Oral arginine, ornithine, aspartate, alanine, glutamate and medium-chain triglycerides all lowered blood ammonia following Gly + Suc administration, with combinations of ornithine-plus-aspartate (Orn + Asp) or ornithine-plus-alanine (Orn + Ala) suppressing levels similar to wild-type. Liver perfusion and portal vein-arterial amino acid differences suggest that oral aspartate, similar to alanine, likely activated ureagenesis from ammonia and lowered the cytosolic NADH/NAD+ ratio through conversion to alanine in the small intestine. In conclusion, Gly + Suc administration induces a more severe hyperammonemic state in double-KO mice that Orn + Asp or Orn + Ala both effectively suppress. Aspartate-to-alanine conversion in the small intestine allows for effective oral administration of either, demonstrating a pivotal role of inter-organ aspartate metabolism for the treatment of citrin deficiency.
Novel blaCTX-M variants and genotype-phenotype correlations among clinical isolates of extended spectrum beta lactamase-producing Escherichia coli
Authors: Ramadan Ahmed A. , Abdelaziz Neveen A. , Amin Magdy A. , Aziz Ramy K. 
Published: March 2019

AbstractThe rapid emergence of multiresistant microbial pathogens, dubbed superbugs, is a serious threat to human health. Extended spectrum beta lactamase (ESBL)-producing Escherichia coli is a superbug causing worldwide outbreaks, necessitating timely and accurate tracking of resistant strains. Accordingly, this study was designed to investigate the spread of ESBL-producing Escherichia coli isolates, to analyze the effect of different genotypic and phenotypic factors on in vitro resistance patterns, and to assess the diagnostic value of commonly used ESBL genetic markers. For that purpose, we cultured 250 clinical isolates and screened their susceptibility to beta-lactam antibiotics. Among 12 antibiotics screened, only imipenem seems to have remained resilient. We subsequently analyzed the ESBL phenotype of Escherichia coli isolates and examined potential associations between their resistance phenotypes and patient-related factors. ESBL genotyping of 198 multiresistant isolates indicated that 179 contained at least one blaCTX-M gene. As we statistically dissected the data, we found associations between overall resistance and body site / type of disease. Additionally, we confirmed the diagnostic value of testing both blaCTX-M-1 and blaCTX-M-15 in providing better prediction of overall resistance. Finally, on sequencing the amplification products of detected blaCTX-M genes, we discovered two novel variants, which we named blaCTX-M-14.2 and blaCTX-M-15.2.
Language Outcomes in Adults with a History of Institutionalization: Behavioral and Neurophysiological Characterization
Authors: Kornilov Sergey A. , Zhukova Marina A. , Ovchinnikova Irina V. , Golovanova Irina V. , Naumova Oxana Yu. , Logvinenko Tatiana I. , Davydova Aleksandra O. , Petrov Maxim V. , Chumakova Maria A. , Grigorenko Elena L. 
Published: March 2019

AbstractImpoverished early care environments are associated with developmental deficits in children raised in institutional settings. Despite the accumulation of evidence regarding deficits in general cognitive functioning in this population, less is known about the impact of institutionalization on language development at the level of brain and behavior. We examined language outcomes in young adults and adolescents raised in institutions (n = 23) as compared to their socioeconomic status and age peers raised in biological families (n = 24) using a behavioral language assessment and linguistic event-related potentials (ERPs). Controlling for intelligence, adults with a history of institutionalization demonstrated deficits in lexical and grammatical development and spelling. Analyses of ERP data revealed significant group differences in the dynamic processing of linguistic stimuli. Adults with a history of institutionalization displayed reduced neural sensitivity to violations of word expectancy, leading to reduced condition effects for temporo-spatial factors that tentatively corresponded to the N200, P300/N400, and phonological mismatch negativity. The results suggest that language is a vulnerable domain in adults with a history of institutionalization, the deficits in which are not explained by general developmental delays, and point to the pivotal role of early linguistic environment in the development of the neural networks involved in language processing.
Acute sublethal exposure to toxic heavy metals alters honey bee (Apis mellifera) feeding behavior
Authors: Burden Christina M. , Morgan Mira O. , Hladun Kristen R. , Amdam Gro V. , Trumble John J. , Smith Brian H. 
Published: March 2019

AbstractHeavy metal toxicity is an ecological concern in regions affected by processes like mining, industry, and agriculture. At sufficiently high concentrations, heavy metals are lethal to honey bees, but little is known about how sublethal doses affect honey bees or whether they will consume contaminated food. We investigated whether honey bees reject sucrose solutions contaminated with three heavy metals – cadmium, copper, and lead – as a measure of their ability to detect the metals, and whether ingesting these metals altered the bees’ sucrose sensitivity. The metals elicited three different response profiles in honey bees. Cadmium was not rejected in any of the assays, and ingesting cadmium did not alter sucrose sensitivity. Copper was rejected following antennal stimulation, but was readily consumed following proboscis stimulation. Ingestion of copper did not alter sucrose sensitivity. Lead appeared to be palatable at some concentrations and altered the bees’ sensitivity to and/or valuation of sucrose following antennal stimulation or ingestion of the metal. These differences likely represent unique mechanisms for detecting each metal and the pathology of toxicity. The bees’ ability to detect and consume these toxic metals highlights the risk of exposure to these elements for bees living in or near contaminated environments.
Characterization of polydactyly chondrocytes and their use in cartilage engineering
Authors: Cavalli Emma , Levinson Clara , Hertl Matthias , Broguiere Nicolas , Brück Oscar , Mustjoki Satu , Gerstenberg Anja , Weber Daniel , Salzmann Gian , Steinwachs Matthias , Barreto Gonçalo , Zenobi-Wong Marcy 
Published: March 2019

AbstractTreating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-β transduced polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns. In this study, we characterized infant, polydactyly chondrocytes during in vitro expansion and chondrogenic re-differentiation. Polydactyly chondrocytes have a steady proliferative rate and re-differentiate in 3D pellet culture after up to five passages. Additionally, we demonstrated that polydactyly chondrocytes produce cartilage-like matrix in a hyaluronan-based hydrogel, namely transglutaminase cross-linked hyaluronic acid (HA-TG). We utilized the versatility of TG cross-linking to augment the hydrogels with heparin moieties. The heparin chains allowed us to load the scaffolds with TGF-β1, which induced cartilage-like matrix deposition both in vitro and in vivo in a subcutaneous mouse model. This strategy introduces the possibility to use infant, polydactyly chondrocytes for the clinical treatment of joint diseases.
Trimethylamine N-Oxide, Circulating Endothelial Progenitor Cells, and Endothelial Function in Patients with Stable Angina
Authors: Chou Ruey-Hsing , Chen Chi-Yu , Chen I-Chun , Huang Hsin-Lei , Lu Ya-Wen , Kuo Chin-Sung , Chang Chun-Chin , Huang Po-Hsun , Chen Jaw-Wen , Lin Shing-Jong 
Published: March 2019

AbstractTrimethylamine N-oxide (TMAO) is a metabolite originated from bacterial metabolism of choline-rich foods. Evidence suggests an association between TMAO and atherosclerosis, but the relationship between TMAO and endothelial progenitor cells (EPCs) remains unclear. This study aimed to identify the relationship between TMAO concentrations, circulating EPCs, and endothelial function in patients with stable angina. Eighty-one stable angina subjects who underwent coronary angiography were enrolled. The circulating EPCs and flow-mediated vasodilation (FMD) were measured to evaluate endothelial function. Plasma TMAO and inflammatory markers, such as hsCRP and IL-1β, were determined. Furthermore, the effect of TMAO on EPCs was assessed in vitro. Patients with lower FMD had significantly decreased circulating EPCs, elevated TMAO, hsCRP, and IL-1β concentrations. Plasma TMAO levels were negatively correlated with circulating EPC numbers and the FMD, and positively correlated with hsCRP, IL-1β concentrations. In in vitro studies, incubation of TMAO in cultured EPCs promoted cellular inflammation, elevated oxidative stress, and suppressed EPC functions. Enhanced plasma TMAO levels were associated with reduced circulating EPCs numbers, endothelial dysfunction, and more adverse cardiovascular events. These findings provided evidence of TMAO’s toxicity on EPCs, and delivered new insight into the mechanism of TMAO-mediated atherosclerosis, which could be derived from TMAO-downregulated EPC functions.
The relationship between physiological and mechanical properties of Acer platanoides L. and Tilia cordata Mill. leaves and their seasonal senescence
Authors: Ciupak Anna , Dziwulska-Hunek Agata , Gładyszewska Bożena , Kwaśniewska Anita 
Published: March 2019

AbstractThe seasonal senescence of leaves in the phenological cycle coincides with the change of their strength properties which determine resistance to environmental conditions and the efficiency of the photosynthesis process. That affects the development, growth and condition of the plant. Therefore, the aim of this paper was to observe and compare the results of strength tests performed on the leaves of two species of trees popular in Poland - lime and maple. As well as chlorophyll fluorescence and photosynthetic pigments content in the context of the changes occurring during the entire leaf life cycle. Obtained results showed that the strength properties of the tested leaves reached the minimum values in spring and the maximum in the summer similarly to the leaf greenness index. Whereas the fluorescence increased which the seasonal senescence in opposition to the photosynthesis efficiency of the leaves. Collected data revealed that strength parameters and photosynthetic pigment content were significantly higher for maple leaves than for lime leaves. Studies showed differences between physiological and mechanical properties of the leaves of two trees species, even if they grew under the same environmental conditions. It is concluded from the results that phenotype and physical parameters of leaves are related to seasonal senescence.
Association between self-reported physical activity and incident atrial fibrillation in a young Korean population
Authors: Lee Sung Ho , Ryu Seungho , Lee Jong-Young , Seo Dae Chul , Kim Byung Jin , Sung Ki-Chul 
Published: March 2019

AbstractThe association between physical activity (PA) and atrial fibrillation (AF) remains unclear. We thus investigated association of PA with the development of AF. Type and duration data for PA were acquired from 211,992 AF-free individuals using the validated Korean version of the International Physical Activity Questionnaire Short From between March 2002 and December 2014. Individuals were divided into four groups according to self-reported PA level and previous international PA guidelines: no PA with a sedentary lifestyle, insufficient PA, sufficient PA, and health-enhancing PA. AF was diagnosed by annual 12-lead electrocardiogram. During a median follow-up of 5.6 years, AF occurred in 304 participants (annual AF incidence rate 2.5/10,000 person-years). After adjusting for age and sex, PA level was not associated with AF incidence (P for trend = 0.26). The multivariable-adjusted hazard ratios (95% confidence interval) for incidental AF was 1.00 (0.74–1.37) for the insufficient PA group, 1.34 (0.91–1.97) for the sufficient PA group, and 1.27 (0.72–2.23) for the health-enhancing PA group compared with the no PA group (P for trend = 0.18). Thus, our study does not support an association between the risk of AF and PA level in a young Korean population.
Real-world evidence and clinical observations of the treatment of advanced non-small cell lung cancer with PD-1/PD-L1 inhibitors
Authors: Song Peng , Zhang Jingcheng , Shang Congcong , Zhang Li 
Published: March 2019

AbstractTo summarize the therapeutic effects of PD-1/PD-L1 inhibitors on patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting, we attempted to identify potential molecular biomarkers or clinical factors that reflected the therapeutic effect. The medical records of patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitors were obtained from the outpatient department or inpatient department of Peking Union Medical College Hospital from August 1, 2015, to January 1, 2018. Our follow-up continued until May 1,2018. We chose overall survival (OS) as the primary observation endpoint and progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety as the secondary observation endpoints. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan-Meier method was used to generate survival curves, and we compared the influence of different factors on PFS and OS by the log-rank test. The median follow-up time was 11 months. At the end of the follow-up, 24 patients (61.5%) were still undergoing immunotherapy, and 7 patients (17.9%) had died. Twenty-six cases (66.7%) employed PD-1/PD-L1 inhibitors as first-line treatment, and 7 cases (17.9%) employed PD-1/PD-L1 inhibitors as second-line treatment. Only 6 cases (15.4%) employed PD-1/PD-L1 inhibitors as third-line treatment. Therapeutic effect evaluation: Complete response (CR): 1 case (2.6%). Partial response (PR): 10 cases (25.6%). Stable disease (SD): 16 cases (41.0%). Progressive disease (PD): 12 cases (30.8%). The ORR was 28.2%, and DCR was 69.2%. The median PFS was 25.5 months (95% CI 6.8–44.1 months), which failed to reach the median OS. PD-1/PD-L1 inhibitor treatment is more effective for advanced non-small cell lung cancer patients in a real-world setting than in clinical trials; PD-1/PD-L1 inhibitor treatment is more effective for people who are over 70 than for people who are under 70. Additionally, patients who are over 75 years old have a higher response rate, suggesting that elderly patients may receive more benefits from immunotherapy; Patients who have an epidermal growth factor receptor (EGFR) mutation (+) may benefit from immunotherapy after treatment with a tyrosine kinase inhibitor (TKI). It is essential to identify these potential patients from the entire patient pool; PD-1 may have a certain curative effect on brain metastases from NSCLC. Local radiotherapy may help to improve PD-1 intracranial efficacy.