bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zircon U–Pb SHRIMP and monazite EPMA U–Th–total Pb geochronology of granulites of the western boundary, Eastern Ghats Belt, India: a new possibility for Neoproterozoic exhumation history
Authors: Chatterjee A. , Das K. , Bose S. , Ganguly P. , Hidaka H. 
Published: April 2017

Abstract
We present detailed and high-precision geochronological data on granulites occurring along the western boundary of the Eastern Ghats Belt, India. Age data on systematically sampled rocks coupled with geochemical observation have a potential to unravel the overprinted tectonothermal events operated during Precambrian time. Zircon U–Pb SHRIMP and monazite electron probe microanalysis (EPMA) U–Th–total Pb analyses, chemical zoning, microtextural investigation, and pressure–temperature calculations were carried out on samples of four different rock types. Inherited zircons from migmatitic quartzofeldspathic gneiss and mafic granulite yielded ages of approximately 2900–2350 Ma, representing an older crustal component. The age of granulite metamorphism recorded from charnockite and pelitic granulite ranges between approximately 950 and 930 Ma (from zircon and monazite). A possible decompression event from this area that occurred during Rodinia break-up is recorded from the Y-rich zones of monazite closely associated with porphyroblastic garnet in pelitic granulite and dates from approximately 800 to 750 Ma. Zircon grains of charnockite also yield a similar age. The youngest age of approximately 525–510 Ma documented from the monazite grains of migmatitic quartzofeldspathic gneiss and pelitic granulite, along with a spot age from zircon of migmatitic quartzofeldspathic gneiss, testifies to the final assembly of East Antarctica with cratonic India as a part of East Gondwana.
Refined geological history of the polyphase plutonometamorphic complex in the Thala Hills area (Enderby Land, East Antarctica) from zircon SHRIMP dating and implications for Neoproterozoic amalgamation of Gondwanaland
Authors: Mikhalsky Evgeniy , Krylov Dmitry , Rodionov Nickolay , Presnyakov Sergey , Skublov Sergey , Myasnikov Oleg 
Published: April 2017

Abstract

The Thala Hills area occupies a key position in Gondwanaland reconstructions near the India–Sri Lanka–Antarctica junction. We present U–Pb zircon isotopic age determinations from SHRIMP II obtained on four granite gneiss samples. Three high-temperature tectonomagmatic episodes may be distinguished in the study area at
c.
980–970,
c.
780–720 and
c.
545–530 Ma. The
c.
980–970 Ma event corresponds to the Rayner Structural Episode that affected East Antarctica, including the Sør Rondane Mountains to the west and Kemp Land to the east. The
c.
780–720 Ma episode included two events at approximately 780 Ma (high-grade anatexis) and 720 Ma (syntectonic granitoid emplacement), and was roughly coeval with tectonomagmatic events in Dronning Maud Land of East Antarctica, as well as in other Gondwanaland regions, such as Madagascar, Sri Lanka and eastern Africa. The
c.
780–720 Ma episode may be correlated with the East African Orogeny. These correlations argue for a similar geological evolution and conjugate position for Dronning Maud Land and Enderby Land despite a postulated Cambrian Lützow–Holm Bay suture separating them. The Cambrian (
c.
545–530 Ma) episode was manifested by high-grade anatexis that confirms previously identified late Neoproterozoic–Cambrian tectonothermal activities in the study area.

Supplementary material:
Trace element compositions of zircons and whole-rock chemical compositions obtained by previous studies are available at
https://doi.org/10.6084/m9.figshare.c.3738332
The geology and geochemistry of the Straumsnutane Formation, Straumsnutane, western Dronning Maud Land, Antarctica and its tectonic setting on the western margin of the Kalahari Craton: additional evidence linking it to the Umkondo Large Igneous Province
Authors: Moabi Neo G. , Grantham Geoffrey H. , Roberts James , Le Roux Petrus 
Published: April 2017

Abstract
The study focuses on whole-rock major and trace element chemistry, as well as radiogenic isotope data from the Straumsnutane Formation lavas in western Dronning Maud Land, Antarctica. The data are compared with those from the Espungabera Formation lavas of central Mozambique, published data from the Borgmassivet intrusions in Dronning Maud Land, Antarctica and other intrusions in southern Africa which are correlated with the approximately 1100 Ma Umkondo Igneous Province.
Petrographical studies indicate that the Straumsnutane lavas are dominated by plagioclase, clinopyroxene, amphibole and Fe–Ti oxides. Secondary mineral assemblages include chlorite, pumpellyite, white mica and epidote, indicating that the Straumsnutane lavas have been metamorphosed under low-grade greenschist-facies conditions followed by retrograde prehnite–pumpellyite-facies conditions.
The chemical data for the Straumsnutane Formation lavas are dominantly tholeiitic and basaltic andesitic in composition, and indicate that they are of continental origin.

Trace element ratio values for the Straumsnutane lavas suggest that fractional crystallization and/or crustal contamination have been significant processes in the magma evolution. Low to high
87
Sr/
86
Sr isotopic ratios (0.682–0.720) are evident from the Straumsnutane lavas suggesting varying degrees of hydrothermal alteration/low-grade metamorphism. The calculated
87
Sr/
86
Sr values and the negative
ε
Nd values at 1100 Ma suggest contamination by older continental crust during the genesis of the Straumsnutane Formation lavas. Isotopic modelling shows that the Straumsnutane lavas may have been formed from the mixing of a mid-ocean ridge basalt (MORB)-like source with approximately 4% of older crust similar to the Messica Granite Gneiss of central Mozambique. Comparison of the geochemical data and petrography of the Straumsnutane lavas with those of the Espungabera Formation lavas of central Mozambique shows that they are similar. Additional comparisons show that the Straumsnutane lavas are geochemically similar to rock units of the Umkondo Igneous Province in southern Africa. It is therefore concluded that the Straumsnutane Formation lavas also formed part of the Umkondo Igneous Province.
WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in obese humans
Authors: Karki Shakun , Ngo Doan T. M. , Farb Melissa G. , Park Song Young , Saggese Samantha M. , Hamburg Naomi M. , Carmine Brian , Hess Donald T. , Walsh Kenneth , Gokce Noyan 
Published: April 2017

Experimental studies have suggested that Wingless-related integration site 5A (WNT5A) is a proinflammatory secreted protein that is associated with metabolic dysfunction in obesity. Impaired angiogenesis in fat depots has been implicated in the development of adipose tissue capillary rarefaction, hypoxia, inflammation, and metabolic dysfunction. We have recently demonstrated that impaired adipose tissue angiogenesis is associated with overexpression of antiangiogenic factor VEGF-A165b in human fat and the systemic circulation. In the present study, we postulated that upregulation of WNT5A is associated with angiogenic dysfunction and examined its role in regulating VEGF-A165b expression in human obesity. We biopsied subcutaneous and visceral adipose tissue from 38 obese individuals (body mass index: 44 ± 7 kg/m2, age: 37 ± 11 yr) during planned bariatric surgery and characterized depot-specific protein expression of VEGF-A165b and WNT5A using Western blot analysis. In both subcutaneous and visceral fat, VEGF-A165b expression correlated strongly with WNT5A protein ( r = 0.9, P < 0.001). In subcutaneous adipose tissue where angiogenic capacity is greater than in the visceral depot, exogenous human recombinant WNT5A increased VEGF-A165b expression in both whole adipose tissue and isolated vascular endothelial cell fractions ( P < 0.01 and P < 0.05, respectively). This was associated with markedly blunted angiogenic capillary sprout formation in human fat pad explants. Moreover, recombinant WNT5A increased secretion of soluble fms-like tyrosine kinase-1, a negative regulator of angiogenesis, in the sprout media ( P < 0.01). Both VEGF-A165b-neutralizing antibody and secreted frizzled-related protein 5, which acts as a decoy receptor for WNT5A, significantly improved capillary sprout formation and reduced soluble fms-like tyrosine kinase-1 production ( P < 0.05). We demonstrated a significant regulatory nexus between WNT5A and antiangiogenic VEGF-A165b in the adipose tissue of obese subjects that was linked to angiogenic dysfunction. Elevated WNT5A expression in obesity may function as a negative regulator of angiogenesis. NEW & NOTEWORTHY Wingless-related integration site 5a (WNT5A) negatively regulates adipose tissue angiogenesis via VEGF-A165b in human obesity.
Assessment of tongue mechanical properties using different contraction tasks
Authors: Li Wen-Yang , Gakwaya Simon , Saey Didier , Sériès Frédéric 
Published: April 2017

Inadequate upper airway (UA) dilator muscle function may play an important role in the pathophysiology of obstructive sleep apnea (OSA). To date, tongue mechanical properties have been assessed mainly using protrusion protocol with conflicting results. Performance during elevation tasks among patients with OSA remains unknown. This study aimed at assessing tongue muscle strength, strength stability, endurance time, fatigue indices, and total muscle work, using elevation and protrusion tasks with repetitive isometric fatiguing contractions in 12 normal plus mild, 17 moderate, and 11 severe patients with OSA, and to assess the influence of body mass index (BMI) and age. Endurance time was longer in protrusion than elevation task ( P = 0.01). In both tasks, endurance time was negatively correlated with baseline value of strength coefficient of variation ( P < 0.01). Compared with other groups, patients with moderate OSA had the lowest total muscle work for protrusion ( P = 0.01) and shortest endurance time ( P = 0.04), regardless of the type of task. Additionally, in patients with moderate-severe OSA, the total muscle work for both tasks was lower in nonobese compared with obese ( P < 0.05). Total muscle work for protrusion was positively correlated with apnea hypopnea index (AHI) in obese subjects ( P < 0.01). Endurance time was shorter ( P < 0.01) and recovery time longer ( P = 0.02) in the old compared with young subjects. In conclusion, the tongue is more prone to fatigue during the elevation task and in patients with moderate OSA. Obesity appeared to prevent alteration of tongue mechanical properties in patients with OSA. Baseline strength stability and endurance were related, illustrating the role of central neuromuscular output in tongue resistance to fatigue.NEW & NOTEWORTHY To our knowledge, this is the first study to assess and compare tongue function using both elevation and protrusion tasks with repetitive isometric fatiguing contractions in subjects with different OSA status. Tongue mechanical performance seemed to differ between protrusion and elevation tasks and depend on the severity of OSA.
Variability in Chromatin Architecture and Associated DNA Repair at Genomic Positions Containing Somatic Mutations
Authors: Lim Byungho , Mun Jihyeob , Kim Yong Sung , Kim Seon-Young 
Published: April 2017

Abstract
Dynamic chromatin structures result in differential chemical reactivity to mutational processes throughout the genome. To identify chromatin features responsible for mutagenesis, we compared chromatin architecture around single-nucleotide variants (SNV), insertion/deletions (indels), and their context-matched, nonmutated positions. We found epigenetic differences between genomic regions containing missense SNVs and those containing frameshift indels across multiple cancer types. Levels of active histone marks were higher around frameshift indels than around missense SNV, whereas repressive histone marks exhibited the reverse trend. Accumulation of repressive histone marks and nucleosomes distinguished mutated positions (both SNV and indels) from the context-matched, nonmutated positions, whereas active marks were associated with substitution- and cancer type–specific mutagenesis. We also explained mutagenesis based on genome maintenance mechanisms, including nucleotide excision repair (NER), mismatch repair (MMR), and DNA polymerase epsilon (POLE). Regional NER variation correlated strongly with chromatin features; NER machineries exhibited shifted or depleted binding around SNV, resulting in decreased NER at mutation positions, especially at sites of recurrent mutations. MMR-deficient tumors selectively acquired SNV in regions with high active histone marks, especially H3K36me3, whereas POLE-deficient tumors selectively acquired indels and SNV in regions with low active histone marks. These findings demonstrate the importance of fine-scaled chromatin structures and associated DNA repair mechanisms in mutagenesis. Cancer Res; 77(11); 2822–33. ©2017 AACR.
Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination
Authors: Batich Kristen A. , Reap Elizabeth A. , Archer Gary E. , Sanchez-Perez Luis , Nair Smita K. , Schmittling Robert J. , Norberg Pam , Xie Weihua , Herndon James E. , Healy Patrick , McLendon Roger E. , Friedman Allan H. , Friedman Henry S. , Bigner Darell , Vlahovic Gordana , Mitchell Duane A. , Sampson John H. 
Published: April 2017

Abstract
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS).
Experimental Design: Following standard-of-care, 11 patients with newly diagnosed glioblastoma received DI-TMZ (100 mg/m2/d × 21 days per cycle) with at least three vaccines of pp65 lysosome–associated membrane glycoprotein mRNA-pulsed DCs admixed with GM-CSF on day 23 ± 1 of each cycle. Thereafter, monthly DI-TMZ cycles and pp65-DCs were continued if patients had not progressed.
Results: Following DI-TMZ cycle 1 and three doses of pp65-DCs, pp65 cellular responses significantly increased. After DI-TMZ, both the proportion and proliferation of regulatory T cells (Tregs) increased and remained elevated with serial DI-TMZ cycles. Median PFS and OS were 25.3 months [95% confidence interval (CI), 11.0–∞] and 41.1 months (95% CI, 21.6–∞), exceeding survival using recursive partitioning analysis and matched historical controls. Four patients remained progression-free at 59 to 64 months from diagnosis. No known prognostic factors [age, Karnofsky performance status (KPS), IDH-1/2 mutation, and MGMT promoter methylation] predicted more favorable outcomes for the patients in this cohort.
Conclusions: Despite increased Treg proportions following DI-TMZ, patients receiving pp65-DCs showed long-term PFS and OS, confirming prior studies targeting cytomegalovirus in glioblastoma. Clin Cancer Res; 23(8); 1898–909. ©2017 AACR.
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non–Small Cell Lung Cancer
Authors: Adeegbe Dennis O. , Liu Yan , Lizotte Patrick H. , Kamihara Yusuke , Aref Amir R. , Almonte Christina , Dries Ruben , Li Yuyang , Liu Shengwu , Wang Xiaoen , Warner-Hatten Tiquella , Castrillon Jessica , Yuan Guo-Cheng , Poudel-Neupane Neermala , Zhang Haikuo , Guerriero Jennifer L. , Han Shiwei , Awad Mark M. , Barbie David A. , Ritz Jerome , Jones Simon S. , Hammerman Peter S. , Bradner James , Quayle Steven N. , Wong Kwok-Kin 
Published: April 2017

AbstractEffective therapies for non–small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein, we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T-cell activation and improved function of antigen-presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+FOXP3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell–mediated antitumor immunity and demonstrate their therapeutic potential for treatment of NSCLC.Significance: Selective inhibition of HDACs and bromodomain proteins modulates tumor-associated immune cells in a manner that favors improved T-cell function and reduced inhibitory cellular mechanisms. These effects facilitated robust antitumor responses in tumor-bearing mice, demonstrating the therapeutic potential of combining these epigenetic modulators for the treatment of NSCLC. Cancer Discov; 7(8); 852–67. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 783
Epigenetic Identity in AML Depends on Disruption of Nonpromoter Regulatory Elements and Is Affected by Antagonistic Effects of Mutations in Epigenetic Modifiers
Authors: Glass Jacob L. , Hassane Duane , Wouters Bas J. , Kunimoto Hiroyoshi , Avellino Roberto , Garrett-Bakelman Francine E. , Guryanova Olga A. , Bowman Robert , Redlich Shira , Intlekofer Andrew M. , Meydan Cem , Qin Tingting , Fall Mame , Alonso Alicia , Guzman Monica L. , Valk Peter J.M. , Thompson Craig B. , Levine Ross , Elemento Olivier , Delwel Ruud , Melnick Ari , Figueroa Maria E. 
Published: April 2017

Abstract
We performed cytosine methylation sequencing on genetically diverse patients with acute myeloid leukemia (AML) and found leukemic DNA methylation patterning is primarily driven by nonpromoter regulatory elements and CpG shores. Enhancers displayed stronger differential methylation than promoters, consisting predominantly of hypomethylation. AMLs with dominant hypermethylation featured greater epigenetic disruption of promoters, whereas those with dominant hypomethylation displayed greater disruption of distal and intronic regions. Mutations in IDH and DNMT3A had opposing and mutually exclusive effects on the epigenome. Notably, co-occurrence of both mutations resulted in epigenetic antagonism, with most CpGs affected by either mutation alone no longer affected in double-mutant AMLs. Importantly, this epigenetic antagonism precedes malignant transformation and can be observed in preleukemic LSK cells from Idh2R140Q or Dnmt3aR882H single-mutant and Idh2R140Q/Dnmt3aR882H double-mutant mice. Notably, IDH/DNMT3A double-mutant AMLs manifested upregulation of a RAS signaling signature and displayed unique sensitivity to MEK inhibition ex vivo as compared with AMLs with either single mutation.
Significance: AML is biologically heterogeneous with subtypes characterized by specific genetic and epigenetic abnormalities. Comprehensive DNA methylation profiling revealed that differential methylation of nonpromoter regulatory elements is a driver of epigenetic identity, that gene mutations can be context-dependent, and that co-occurrence of mutations in epigenetic modifiers can result in epigenetic antagonism. Cancer Discov; 7(8); 868–83. ©2017 AACR.
This article is highlighted in the In This Issue feature, p. 783
Effects of Sugar-Sweetened Beverage Consumption on Microvascular and Macrovascular Function in a Healthy Population
Authors: Loader Jordan , Meziat Cindy , Watts Rani , Lorenzen Christian , Sigaudo-Roussel Dominique , Stewart Simon , Reboul Cyril , Meyer Gregory , Walther Guillaume 
Published: April 2017

Objective—
To assess vascular function during acute hyperglycemia induced by commercial sugar-sweetened beverage (SSB) consumption and its effect on underlying mechanisms of the nitric oxide pathway.

Approach and Results—

In a randomized, single-blind, crossover trial, 12 healthy male participants consumed 600 mL (20 oz.) of water or a commercial SSB across 2 visits. Endothelial and vascular smooth muscle functions were assessed in the microcirculation using laser speckle contrast imaging coupled with iontophoresis and in the macrocirculation using brachial artery ultrasound with flow- and nitrate-mediated dilation. Compared with water, SSB consumption impaired microvascular and macrovascular endothelial function as indicated by a decrease in the vascular response to acetylcholine iontophoresis (208.3±24.3 versus 144.2±15.7%,
P
<0.01) and reduced flow-mediated dilation (0.019±0.002 versus 0.014±0.002%/s,
P
<0.01), respectively. Systemic vascular smooth muscle remained preserved. Similar decreases in endothelial function were observed during acute hyperglycemia in an in vivo rat model. However, function was fully restored by treatment with the antioxidants,
N
-acetylcysteine and apocynin. In addition, ex vivo experiments revealed that although the production of reactive oxygen species was increased during acute hyperglycemia, the bioavailability of nitric oxide in the endothelium was decreased, despite no change in the activation state of endothelial nitric oxide synthase.

Conclusions—
To our knowledge, this is the first study to assess the vascular effects of acute hyperglycemia induced by commercial SSB consumption alone. These findings suggest that SSB-mediated endothelial dysfunction is partly due to increased oxidative stress that decreases nitric oxide bioavailability.

Clinical Trial Registration—

URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366442&isReview=true
. Australian New Zealand Clinical Trials Registry Number: ACTRN12614000614695.