bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed
Authors: Rezaei Simin D. , Lu Hao K. , Chang J. Judy , Rhodes Ajantha , Lewin Sharon R. , Cameron Paul U. 
Published: April 2018

ABSTRACT

HIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4
+
T cells. The induction of virus expression from latently infected cells occurs following T cell receptor (TCR) activation, but not all latently infected cells respond to TCR stimulation. We compared two models of latently infected cells using an enhanced green fluorescent protein (EGFP) reporter virus to infect CCL19-treated resting CD4
+
(rCD4
+
) T cells (preactivation latency) or activated CD4
+
T cells that returned to a resting state (postactivation latency). We isolated latently infected cells by sorting for EGFP-negative (EGFP
−
) cells after infection. These cells were cultured with antivirals and stimulated with anti-CD3/anti-CD28, mitogens, and latency-reversing agents (LRAs) and cocultured with monocytes and anti-CD3. Spontaneous EGFP expression was more frequent in postactivation than in preactivation latency. Stimulation of latently infected cells with monocytes/anti-CD3 resulted in an increase in EGFP expression compared to that for unstimulated controls using the preactivation latency model but led to a reduction in EGFP expression in the postactivation latency model. The reduced EGFP expression was not associated with reductions in the levels of viral DNA or T cell proliferation but depended on direct contact between monocytes and T cells. Monocytes added to the postactivation latency model during the establishment of latency reduced spontaneous virus expression, suggesting that monocyte-T cell interactions at an early time point postinfection can maintain HIV latency. This direct comparison of pre- and postactivation latency suggests that effective strategies needed to reverse latency will depend on how latency is established.

IMPORTANCE
One strategy being evaluated to eliminate latently infected cells that persist in HIV-infected individuals on antiretroviral therapy (ART) is to activate HIV expression or production with the goal of inducing virus-mediated cytolysis or immune-mediated clearance of infected cells. The gold standard for the activation of latent virus is T cell receptor stimulation with anti-CD3/anti-CD28. However, this stimulus activates only a small proportion of latently infected cells. We show clear differences in the responses of latently infected cells to activating stimuli based on how latent infection is established, an observation that may potentially explain the persistence of noninduced intact proviruses in HIV-infected individuals on ART.
Arc magmatism, tectonism, and tempos in Mesozoic arc crustal sections of the Peninsular and Transverse Ranges, southern California, USA
Authors: Paterson Scott , Clausen Ben , Memeti Vali , Schwartz Joshua J. 
Published: April 2018

ABSTRACT
Welcome to our three-day field trip aimed at exploring Mesozoic magmatism and tectonism in southern California. The broader southern California area is a great place to study Cordilleran-style continental margin arcs built across diverse basements ranging from thinner oceanic to thicker continental crust. We will weave together several themes during this trip: (1) spatial variations, including in the vertical dimension, of arc magmatic and tectonic systems; (2) volcanic-plutonic links; (3) pluton sizes and shapes; (4) emplacement and tectonic/plutonic mass balance issues; and (5) arc magmatic and tectonic tempos. While doing so we plan to discuss/ examine the main components of southern California Mesozoic magmatic systems while discussing temporally and spatially variable (1) melt sources, (2) processes in crustal columns, and (3) tectonic activity, all of which lead to the final preserved arcs.
Bedrock and detrital zircon age patterns in a broad corridor across southern California define magmatic flare-up maxima in the Mojave area at ca. 250 Ma in a SE migrating arc, at ca. 170 Ma in a westward migrating arc, at ca. 100 Ma in the eastward migrating Peninsular Ranges Batholith (PRB), extending from just south of the Transverse Ranges and into Baja California, and additional smaller maxima at 81 and 73 Ma in the Transverse Ranges and Joshua Tree regions that may reflect the western edge of a broad region of melting and magmatism throughout the Basin and Range area.
On this trip we will integrate studies from different areas of these Mesozoic arcs including Baja California (Paterson), the northern PRB (Clausen), the San Gabriel Mountains (Schwartz), and the Joshua Tree National Park area (Memeti and Paterson) with a wealth of new data being published by other groups. Day 1 will examine aspects of the Cretaceous PRB in the Perris block where the edge of the western belt and transition zone is exposed. On Days 2 and 3 we will examine parts of two tilted crustal sections, one in the eastern San Gabriel Mountains and the other in the Little San Bernardino Mountains and Joshua Tree National Park. While visiting these crustal sections we will discuss Late Cretaceous to Early Tertiary events to explore why crustal melting and magma emplacement occurred both inboard and post the main magmatic flare-ups in regions that usually are thought to have transitioned into cold fore arc.
β-catenin-activated hepatocellular carcinomas are addicted to fatty acids
Authors: Senni Nadia , Savall Mathilde , Cabrerizo Granados David , Alves-Guerra Marie-Clotilde , Sartor Chiara , Lagoutte Isabelle , Gougelet Angélique , Terris Benoit , Gilgenkrantz Hélène , Perret Christine , Colnot Sabine , Bossard Pascale 
Published: April 2018

ObjectivesCTNNB1-mutated hepatocellular carcinomas (HCCs) constitute a major part of human HCC and are largely inaccessible to target therapy. Yet, little is known about the metabolic reprogramming induced by β-catenin oncogenic activation in the liver. We aimed to decipher such reprogramming and assess whether it may represent a new avenue for targeted therapy of CTNNB1-mutated HCC.DesignWe used mice with hepatocyte-specific oncogenic activation of β-catenin to evaluate metabolic reprogramming using metabolic fluxes on tumourous explants and primary hepatocytes. We assess the role of Pparα in knock-out mice and analysed the consequences of fatty acid oxidation (FAO) using etomoxir. We explored the expression of the FAO pathway in an annotated human HCC dataset.Resultsβ-catenin-activated HCC were not glycolytic but intensively oxidised fatty acids. We found that Pparα is a β-catenin target involved in FAO metabolic reprograming. Deletion of Pparα was sufficient to block the initiation and progression of β-catenin-dependent HCC development. FAO was also enriched in human CTNNB1-mutated HCC, under the control of the transcription factor PPARα.ConclusionsFAO induced by β-catenin oncogenic activation in the liver is the driving force of the β-catenin-induced HCC. Inhibiting FAO by genetic and pharmacological approaches blocks HCC development, showing that inhibition of FAO is a suitable therapeutic approach for CTNNB1-mutated HCC.
Comprehensive analysis of the mutation spectrum in 301 German ALS families
Authors: Müller Kathrin , Brenner David , Weydt Patrick , Meyer Thomas , Grehl Torsten , Petri Susanne , Grosskreutz Julian , Schuster Joachim , Volk Alexander E , Borck Guntram , Kubisch Christian , Klopstock Thomas , Zeller Daniel , Jablonka Sibylle , Sendtner Michael , Klebe Stephan , Knehr Antje , Günther Kornelia , Weis Joachim , Claeys Kristl G , Schrank Berthold , Sperfeld Anne-Dorte , Hübers Annemarie , Otto Markus , Dorst Johannes , Meitinger Thomas , Strom Tim M , Andersen Peter M , Ludolph Albert C , Weishaupt Jochen H 
Published: April 2018

ObjectivesRecent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.MethodsHere we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.Results49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.ConclusionsWe here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.
Update of an occupational asthma-specific job exposure matrix to assess exposure to 30 specific agents
Authors: Le Moual Nicole , Zock Jan-Paul , Dumas Orianne , Lytras Theodore , Andersson Eva , Lillienberg Linnéa , Schlünssen Vivi , Benke Geza , Kromhout Hans 
Published: April 2018

ObjectivesWe aimed to update an asthmagen job exposure matrix (JEM) developed in the late 1990s. Main reasons were: the number of suspected and recognised asthmagens has since tripled; understanding of the aetiological role of irritants in asthma and methodological insights in application of JEMs have emerged in the period.MethodsFor each agent of the new occupational asthma-specific JEM (OAsJEM), a working group of three experts out of eight evaluated exposure for each International Standard Classification of Occupations, 1988 (ISCO-88) job code into three categories: ‘high’ (high probability of exposure and moderate-to-high intensity), ‘medium’ (low-to-moderate probability or low intensity) and ‘unexposed’. Within a working group, experts evaluated exposures independently from each other. If expert assessments were inconsistent the final decision was taken by consensus. Specificity was favoured over sensitivity, that is, jobs were classified with high exposure only if the probability of exposure was high and the intensity moderate-to-high. In the final review, all experts checked assigned exposures and proposed/improved recommendations for expert re-evaluation after default application of the JEM.ResultsThe OAsJEM covers exposures to 30 sensitisers/irritants, including 12 newly recognised, classified into seven broad groups. Initial agreement between the three experts was mostly fair to moderate (κ values 0.2–0.5). Out of 506 ISCO-88 codes, the majority was classified as unexposed (from 82.6% (organic solvents) to 99.8% (persulfates)) and a minority as ‘high-exposed’ (0.2% (persulfates) to 2.6% (organic solvents)).ConclusionsThe OAsJEM developed to improve occupational exposure assessment may improve evaluations of associations with asthma in epidemiological studies and contribute to assessment of the burden of work-related asthma.
The Posidonia Shale of northern Germany: unconventional oil and gas potential from high-resolution 3D numerical basin modelling of the cross-junction between the eastern Lower Saxony Basin, Pompeckj Block and Gifhorn Trough
Authors: Stock Alexander T. , Littke Ralf 
Published: April 2018

Abstract
A high-resolution three-dimensional (3D) numerical basin model, incorporating the eastern part of the Lower Saxony Basin (LSB), the Gifhorn Trough and parts of the southern Pompeckj Block, was built to reconstruct the thermal and structural evolution of this area. The estimation and calculation of the unconventional oil and gas resource density within the Posidonia Shale source-rock unit was the main objective of this study. Incorporating organic–geochemical data for the Posidonia Shale source-rock units, such as compositional petroleum generation kinetics data, allowed a more accurate prediction of hydrocarbon potential compared to large-scale models of the area, as well as a better prediction of bulk adsorption capacity and adsorbed gas content. For the accurate calculation of oil and gas contents within the source-rock lithologies, mineralogy and physical properties of the rocks, such as compressibility, sorption capacity and porosity, are important as well as organic matter quantity, quality and thermal maturity. These properties in turn are strongly dependent on the vastly different burial/uplift histories within the LSB, Gifhorn Trough and the Pompeckj Block. The Gifhorn Trough, large parts of the Pompeckj Block and the flanks of the LSB are interesting concerning the unconventional oil potential, with current source-rock maturities between 0.65% and 1.2% vitrinite reflectance. Central parts of the LSB and small parts of the Pompeckj Block show inherent unconventional gas potential. Methane adsorption capacity is influenced by the burial/uplift history of the basin, which stresses the importance of structural and geochemical interlocking in understanding unconventional hydrocarbon systems.
The relationship between systematic metamorphic patterns and collisional processes along the Qinling–Sulu–Odesan collisional belt between the North and South China Cratons
Authors: Oh Chang Whan , Lee Byung Choon 
Published: April 2018

Abstract
Along the Qinling–Sulu–Odesan collisional belt, the peak metamorphic conditions reflect systematically changing metamorphic regimes from east to west: ultra-high temperature (UHT) granulite-facies metamorphism in the Odesan area; high pressure (HP) eclogite-facies metamorphism in the Hongseong area; ultra-high pressure (UHP) eclogite-facies metamorphism in the Sulu, Dabie and Hong'an areas; HP eclogite-facies metamorphism in the Tonbai area; epidote–amphibolite- and blueschist facies metamorphism in the Wudang area; and HP granulite-facies metamorphism in the western Qinling area. Additionally, the Triassic post-collisional igneous rocks regionally intruded at both ends of the collision belt, in the west Qinling and Hongseong–Odesan areas. These observations indicate that the following collisional processes occurred along the Qinling–Dabie–Odesan collisional belt. The North China Craton and South China Craton first collided at their eastern margins (the Odesan area) with an angle of approximately 60° between their long axes. Consequently, the amount of oceanic slab subducted before the collision increased from the Odesan area to the Sulu area, resulting in an increase in the depth of slab break-off. After slab break-off occurred in the Sulu area, the lateral tearing force strengthened, decreasing the depth of slab break-off from the Sulu area to the western Qinling area as collision propagated westward.
Peripheral revascularization attenuates the exercise pressor reflex and increases coronary exercise hyperemia in peripheral arterial disease
Authors: Miller Amanda J. , Luck J. Carter , Kim Danielle Jin-Kwang , Leuenberger Urs A. , Aziz Faisal , Radtka John F. , Sinoway Lawrence I. , Muller Matthew D. 
Published: April 2018

Peripheral arterial disease (PAD) is associated with augmented blood pressure (BP) and impaired coronary blood flow responses to exercise, which may increase cardiovascular risk. We investigated the effects of leg revascularization on the BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients (11 men, 66 ± 2 yr) performed single-leg plantar flexion exercise 24 h before and 1 mo following leg revascularization. BP and heart rate (HR) were measured continuously, and rate pressure product (systolic BP × HR) was calculated as an index of myocardial oxygen demand. Coronary blood velocity was obtained by transthoracic Doppler echocardiography in 8/17 subjects. The mean BP response to plantar flexion exercise was attenuated by leg revascularization (pre-revascularization: 15 ± 4 vs. post-revascularization: 7 ± 3 mmHg, P = 0.025). The HR response to plantar flexion was also attenuated following leg revascularization (pre-revascularization: 9 ± 1 vs. post-revascularization: 6 ± 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise was greater at the post-revascularization visit: 4 ± 1 vs. pre-revascularization: −1 ± 2 cm/s ( P = 0.038), even though the change in rate pressure product was not greater following revascularization in these subjects (pre-revascularization: 2,796 ± 871 vs. post-revascularization: 1,766 ± 378 mmHg·beats/min, P = 0.082). These data suggest that leg revascularization alters reflex control of BP, HR, and coronary blood flow in response to exercise in patients with PAD. NEW & NOTEWORTHY We found that peripheral revascularization procedures lowered exercise blood pressure and improved coronary blood flow in patients with peripheral arterial disease.
Transfer coefficients better reflect emphysematous changes than carbon monoxide diffusing capacity in obstructive lung diseases
Authors: Shimizu Kaoruko , Konno Satoshi , Makita Hironi , Kimura Hirokazu , Kimura Hiroki , Suzuki Masaru , Nishimura Masaharu 
Published: April 2018

The overlap between asthma and chronic obstructive pulmonary disease (COPD) has attracted the interest of pulmonary physicians; thus, measurement of carbon monoxide diffusion capacity (DLco) and/or transfer coefficients (Kco, DLco/VA) may become valuable in clinical settings. How these parameters behave in chronic obstructive lung diseases is poorly understood. We predicted that Kco might more accurately reflect emphysematous changes in the lungs than DLco. We examined DLco and Kco in nonsmokers and smokers with asthma and investigated their relationships with forced expiratory volume in 1 s (%FEV1) by group. We then selected nonsmokers (As-NS) and smokers with asthma (As-Sm) in both groups and those with COPD while controlling for the degree of airflow limitation across groups. Emphysema volumes [%lung attenuation volume (%LAV)] and percentage of cross-sectional area of small pulmonary vessels <5 mm2(%CSA<5) were measured by computed tomography. In As-NS, %Kco was significantly higher when FEV1% was reduced, but such a correlation was not seen in As-Sm. %Kco successfully differentiated among the three groups when airflow limitation levels were matched. However, %DLc, was significantly reduced only in patients with COPD. Both %LAV and %CSA<5were better correlated with %Kco than with %DLco. There was discordance between %DLCOand %Kco in As-Sm, which was not seen in As-NS. Overall, %Kco better reflects emphysematous changes in obstructive lung diseases than %DLco.NEW & NOTEWORTHY Despite differing behaviors of %Kco and %DLco in several diseases, the characteristics of these parameters have not been fully examined in smokers with asthma. Here, we demonstrated that %Kco is a more sensitive parameter of pathophysiology, better reflecting emphysematous changes in chronic obstructive lung diseases overall, compared with %DLco. Thus, more precise interpretations of %DLco and %Kco may provide clues for understanding the pathophysiology of obstructive lung diseases.
Preliminary evidence of reductive stress in human cytotoxic T cells following exercise
Authors: Wadley Alex J. , Holliday Adrian , Morgan Rhys G. , Heesom Kate J. , Aldred Sarah , Peters Derek M. , Bueno Allain A. , Coles Steven J. 
Published: April 2018

This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained [ n = 9, means ± SD: age 28 ± 5 yr; (body mass index) BMI 23.2 ± 2.6 kg/m2; V̇o2max (maximal oxygen intake)56.9 ± 6.1 ml·kg−1·min−1] and recreationally active (RA, n = 11, means ± SD: age 27 ± 6 yr; BMI 24.2 ± 3.7 kg/m2; V̇o2max 45.1 ± 6.4 ml·kg−1·min−1) participants before and after a maximal aerobic exercise tolerance test. Blood samples were taken before (Pre), during (sample acquired at 70% maximum heart rate), immediately after (Post + 0), and 15 min postexercise (Post + 15). PBMCs were isolated, and reduced thiol analysis [fluorescein-5 maleimide (F5M)] by immunophenotype [cluster of differentiation (CD)3+, CD4+, and CD8+] was performed using flow cytometry. A significant increase in cellular F5M fluorescence was observed in CD3+ T cells at Post + 0, with changes driven to a greater extent by CD8+ T cells (fold change in both groups CD4: +2.3, CD8: +2.8; P < 0.05). Further analysis revealed a population of highly reduced CD8+ T cells (CD8+T-reduced+) that significantly increased from Pre to Post + 0 in RA participants only (RA: +272 cell/µl, P < 0.05). To understand these results further, CD8+T-reduced+ and CD8+T-reduced− cells were analyzed for immunophenotype in response to the same exercise protocol ( n = 6, means ± SD: age 24 ± 5 yr; BMI 25.7 ± 4.1 kg·m−2; V̇o2max 41.33 ± 7.63 ml·kg−1·min−1). CD8+T-reduced+ had significantly less lymphoid homing potential (chemokine receptor type 7) Post + 0 compared with Pre. This study is the first, to our knowledge, to demonstrate that lymphocyte populations become more reductive in response to acute exercise. NEW & NOTEWORTHY The study presented provides the first evidence to suggest that cytotoxic T cells become transiently reductive in healthy individuals following a single bout of cycling. Detection of these cells was enabled via the use of a flow cytometric assay that incorporates the thiol reactive probe fluorescein-5 maleimide. Using this method, transient reductive stress in viable T cells is permissible and provides the basis for further research in the area of exercise immunology.
Serum Exosomal Long Noncoding RNAs ENSG00000258332.1 and LINC00635 for the Diagnosis and Prognosis of Hepatocellular Carcinoma
Authors: Xu Hong , Chen Yueming , Dong Xueyan , Wang Xianjun 
Published: April 2018

Abstract
Background: Increasing studies suggest that long noncoding RNAs (lncRNAs) are involved in carcinogenesis of human cancers and might be used as diagnostic biomarkers for cancers.
Methods: A total of 301 participants were recruited in the first part of the study, including a hepatocellular carcinoma (HCC) group (n = 60), liver cirrhosis (LC) group (n = 85), chronic hepatitis B (CHB) group (n = 96), and healthy subjects (n = 60). In the second part, we collected 55 HCC patients, 60 CHB patients, and 60 healthy subjects as an independent cohort to validate the ability of the experiential lncRNAs for identifying HCC from CHB. A commercial kit was used to isolate serum exosomes and total RNA. The relative levels of lnRNAs and GAPDH mRNA were measured with TaqMan PCR.
Results: The results showed that the levels of ENSG00000258332.1 and LINC00635 in the HCC group were significantly higher than those in the other groups (all P &lt; 0.05). A high ENSG00000258332.1 level in HCC was associated with portal vein tumor emboli, lymph node metastasis, TNM stage, and overall survival (OS; all P &lt; 0.05), and a high LINC00635 level was related to lymph node metastasis, TNM stage, and OS (all P &lt; 0.05). ENSG00000258332.1 discriminated HCC from CHB, gaining an area under the ROC curve (AUC) of 0.719 (cutoff value of 1.345); LINC00635 gained an AUC of 0.750 (cutoff value of 1.690). Furthermore, the AUC for the combination of the 2 lncRNAs and serum AFP (cutoff value of 20 μg/L) was 0.894. The abilities of the 2 lncRNAs for identifying HCC from CHB were validated by an independent cohort.
Conclusions: The results suggested that the combination of serum exosomal ENSG00000258332.1, LINC00635, and AFP may be a valuable assay in diagnosis and prognosis of HCC.
Impact: Our data will shed light on exosomal lncRNAs as biomarkers for HCC. Cancer Epidemiol Biomarkers Prev; 27(6); 710–6. ©2018 AACR.