bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of lamprophyres from the northern margin of the North China Craton: implications for mantle metasomatism
Authors: Niu Xiaolu , Chen Bin , Feng Guangying , Liu Fei , Yang Jingsui 
Published: November 2016

Abundant lamprophyre dykes occur near the northern margin of the North China Craton and offer a unique opportunity to study the nature of the mantle source. The dykes are minettes composed of phlogopite, sanidine and calcite.
40
Ar/
39
Ar dating yields ages of 234 ± 2 and 222 ± 6 Ma. The lamprophyres are near-primary, mantle-derived ultrapotassic melts, having low SiO
2
(31.0 – 41.5 wt%) and high K
2
O (4.40 – 7.12 wt%) contents, high Mg# (62 – 84) and high contents of compatible elements. They are characterized by fractionated rare earth element patterns, radiogenic Sr and unradiogenic Nd isotope compositions (
87
Sr/
86
Sr
i
= 0.7070 – 0.7075; ε
Nd
(
t
) = −12.8 to −9.2). A small amount of mafic crustal rocks (<4.4%) may have been assimilated during magma ascent, as revealed by
187
Os/
188
Os
i
ratios of 0.4548 – 0.8068. These data suggest that the lamprophyres originated from a low degree of partial melting of an enriched subcontinental lithospheric mantle source with abundant phlogopite, clinopyroxene and carbonate. The source has been metasomatized by carbonate- and potassium-rich fluids derived from carbonated sediments recycled via subduction of Palaeo-Mongolian oceanic slab beneath the North China Craton.

Supplementary material:
Microprobe analyses of biotite, feldspar and carbonate,
40
Ar–
39
Ar analytical data, and
36
Ar/
40
Ar v.
39
Ar/
40
Ar inverse isochron diagrams for phlogopite phenocrysts and groundmass from the Datong lamprophyres are available at
https://doi.org/10.6084/m9.figshare.c.3574265
.
Hyperglycemia induces defective Ca2+ homeostasis in cardiomyocytes
Authors: Sorrentino Andrea , Borghetti Giulia , Zhou Yu , Cannata Antonio , Meo Marianna , Signore Sergio , Anversa Piero , Leri Annarosa , Goichberg Polina , Qanud Khaled , Jacobson Jason T. , Hintze Thomas H. , Rota Marcello 
Published: November 2016

Diabetes and other metabolic conditions characterized by elevated blood glucose constitute important risk factors for cardiovascular disease. Hyperglycemia targets myocardial cells rendering ineffective mechanical properties of the heart, but cellular alterations dictating the progressive deterioration of cardiac function with metabolic disorders remain to be clarified. In the current study, we examined the effects of hyperglycemia on cardiac function and myocyte physiology by employing mice with high blood glucose induced by administration of streptozotocin, a compound toxic to insulin-producing β-cells. We found that hyperglycemia initially delayed the electrical recovery of the heart, whereas cardiac function became defective only after ~2 mo with this condition and gradually worsened with time. Prolonged hyperglycemia was associated with increased chamber dilation, thinning of the left ventricle (LV), and myocyte loss. Cardiomyocytes from hyperglycemic mice exhibited defective Ca2+ transients before the appearance of LV systolic defects. Alterations in Ca2+ transients involved enhanced spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR), reduced cytoplasmic Ca2+ clearance, and declined SR Ca2+ load. These defects have important consequences on myocyte contraction, relaxation, and mechanisms of rate adaptation. Collectively, our data indicate that hyperglycemia alters intracellular Ca2+ homeostasis in cardiomyocytes, hindering contractile activity and contributing to the manifestation of the diabetic cardiomyopathy. NEW & NOTEWORTHY We have investigated the effects of hyperglycemia on cardiomyocyte physiology and ventricular function. Our results indicate that defective Ca2+ handling is a critical component of the progressive deterioration of cardiac performance of the diabetic heart.
Neuronal pattern separation of motion-relevant input in LIP activity
Authors: Berberian Nareg , MacPherson Amanda , Giraud Eloïse , Richardson Lydia , Thivierge J.-P. 
Published: November 2016

In various regions of the brain, neurons discriminate sensory stimuli by decreasing the similarity between ambiguous input patterns. Here, we examine whether this process of pattern separation may drive the rapid discrimination of visual motion stimuli in the lateral intraparietal area (LIP). Starting with a simple mean-rate population model that captures neuronal activity in LIP, we show that overlapping input patterns can be reformatted dynamically to give rise to separated patterns of neuronal activity. The population model predicts that a key ingredient of pattern separation is the presence of heterogeneity in the response of individual units. Furthermore, the model proposes that pattern separation relies on heterogeneity in the temporal dynamics of neural activity and not merely in the mean firing rates of individual neurons over time. We confirm these predictions in recordings of macaque LIP neurons and show that the accuracy of pattern separation is a strong predictor of behavioral performance. Overall, results propose that LIP relies on neuronal pattern separation to facilitate decision-relevant discrimination of sensory stimuli. NEW & NOTEWORTHY A new hypothesis is proposed on the role of the lateral intraparietal (LIP) region of cortex during rapid decision making. This hypothesis suggests that LIP alters the representation of ambiguous inputs to reduce their overlap, thus improving sensory discrimination. A combination of computational modeling, theoretical analysis, and electrophysiological data shows that the pattern separation hypothesis links neural activity to behavior and offers novel predictions on the role of LIP during sensory discrimination.
Contextual effects of noise on vocalization encoding in primary auditory cortex
Authors: Ni Ruiye , Bender David A. , Shanechi Amirali M. , Gamble Jeffrey R. , Barbour Dennis L. 
Published: November 2016

Robust auditory perception plays a pivotal function for processing behaviorally relevant sounds, particularly with distractions from the environment. The neuronal coding enabling this ability, however, is still not well understood. In this study, we recorded single-unit activity from the primary auditory cortex (A1) of awake marmoset monkeys ( Callithrix jacchus) while delivering conspecific vocalizations degraded by two different background noises: broadband white noise and vocalization babble. Noise effects on neural representation of target vocalizations were quantified by measuring the responses' similarity to those elicited by natural vocalizations as a function of signal-to-noise ratio. A clustering approach was used to describe the range of response profiles by reducing the population responses to a summary of four response classes (robust, balanced, insensitive, and brittle) under both noise conditions. This clustering approach revealed that, on average, approximately two-thirds of the neurons change their response class when encountering different noises. Therefore, the distortion induced by one particular masking background in single-unit responses is not necessarily predictable from that induced by another, suggesting the low likelihood of a unique group of noise-invariant neurons across different background conditions in A1. Regarding noise influence on neural activities, the brittle response group showed addition of spiking activity both within and between phrases of vocalizations relative to clean vocalizations, whereas the other groups generally showed spiking activity suppression within phrases, and the alteration between phrases was noise dependent. Overall, the variable single-unit responses, yet consistent response types, imply that primate A1 performs scene analysis through the collective activity of multiple neurons. NEW & NOTEWORTHY The understanding of where and how auditory scene analysis is accomplished is of broad interest to neuroscientists. In this paper, we systematically investigated neuronal coding of multiple vocalizations degraded by two distinct noises at various signal-to-noise ratios in nonhuman primates. In the process, we uncovered heterogeneity of single-unit representations for different auditory scenes yet homogeneity of responses across the population.
Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Receptor Upregulation
Authors: Bernichtein Sophie , Pigat Natascha , Barry Delongchamps Nicolas , Boutillon Florence , Verkarre Virginie , Camparo Philippe , Reyes-Gomez Edouard , Méjean Arnaud , Oudard Stéphane M. , Lepicard Eve M. , Viltard Mélanie , Souberbielle Jean-Claude , Friedlander Gérard , Capiod Thierry , Goffin Vincent 
Published: November 2016

Abstract
Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355–65. ©2016 AACR.
Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells
Authors: Sektioglu Ibrahim M. , Carretero Rafael , Bulbuc Nadja , Bald Tobias , Tüting Thomas , Rudensky Alexander Y. , Hämmerling Günter J. 
Published: November 2016

AbstractElevated numbers of regulatory T cells (Treg) in patient tumors are known to inhibit efficient antitumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8+ T-cell–dependent way. In contrast, about 90% Treg depletion obtained in BAC transgenic Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas, demonstrating that residual Tregs were able to control CD8+ T-cell responses against the tumor. Ninety-nine percent of Treg depletion provoked drastic changes in the tumor microenvironment, such as strong infiltration of CD8+ T cells and basophils. Intratumoral basophils enhanced CD8+ T-cell infiltration via production of chemokines CCL3 and CCL4; antibody-based blocking of these chemokines inhibited CD8+ T-cell infiltration. Therapeutic induction of basophilia by IL3/anti-IL3 antibody complexes, combined with transfer of CD8+ T cells, resulted in enhanced T-cell infiltration and tumor rejection. Our study identifies a critical role basophils play in tumor rejection and that this role can be exploited for therapeutic intervention. Cancer Res; 77(2); 291–302. ©2016 AACR.
IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer
Authors: Wang Lei , Miyahira Andrea K. , Simons Diana L. , Lu Xuyang , Chang Andrew Y. , Wang Carrie , Suni Maria A. , Maino Vernon C. , Dirbas Frederick M. , Yim John , Waisman James , Lee Peter P. 
Published: November 2016

AbstractIL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear. Here, we show the IL6 signaling response in peripheral blood T cells is impaired in breast cancer patients and is associated with blunted Th17 differentiation. The mechanism identified involved downregulation of gp130 and IL6Rα in breast cancer patients and was independent of plasma IL6 levels. Importantly, defective IL6 signaling in peripheral blood T cells at diagnosis correlated with worse relapse-free survival. These results indicate that intact IL6 signaling in T cells is important for controlling cancer progression. Furthermore, they highlight a potential for IL6 signaling response in peripheral blood T cells at diagnosis as a predictive biomarker for clinical outcome of breast cancer patients. Cancer Res; 77(5); 1119–26. ©2016 AACR.
Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation and ERBB2 Expression
Authors: Shibata Tomohiro , Watari Kosuke , Izumi Hiroto , Kawahara Akihiko , Hattori Satoshi , Fukumitsu Chihiro , Murakami Yuichi , Takahashi Ryuji , Toh Uhi , Ito Ken-ichi , Ohdo Shigehiro , Tanaka Maki , Kage Masayoshi , Kuwano Michihiko , Ono Mayumi 
Published: November 2016

Abstract
Endocrine therapies effectively improve the outcomes of patients with estrogen receptor (ER)-positive breast cancer. However, the emergence of drug-resistant tumors creates a core clinical challenge. In breast cancer cells rendered resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo. Furthermore, YBX1 overexpression was associated with decreased and increased levels of ER and ERBB2 expression, respectively. In antiestrogen-resistant cells, increased YBX1 phosphorylation was associated with a 4-fold higher degradation rate of ER. Notably, YBX1 bound the ER, leading to its accelerated proteasomal degradation, and induced the transcriptional activation of ERBB2. In parallel fashion, tamoxifen treatment also augmented YBX1 binding to the ERBB2 promoter to induce increased ERBB2 expression. Together, these findings define a mechanism of drug resistance through which YBX1 contributes to antiestrogen bypass in breast cancer cells. Cancer Res; 77(2); 545–56. ©2016 AACR.
Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer
Authors: Koch Maximilian , de Jong Johannes S. , Glatz Jürgen , Symvoulidis Panagiotis , Lamberts Laetitia E. , Adams Arthur L.L. , Kranendonk Mariëtte E.G. , Terwisscha van Scheltinga Anton G.T. , Aichler Michaela , Jansen Liesbeth , de Vries Jakob , Lub-de Hooge Marjolijn N. , Schröder Carolien P. , Jorritsma-Smit Annelies , Linssen Matthijs D. , de Boer Esther , van der Vegt Bert , Nagengast Wouter B. , Elias Sjoerd G. , Oliveira Sabrina , Witkamp Arjen J. , Mali Willem P.T.M. , Van der Wall Elsken , Garcia-Allende P. Beatriz , van Diest Paul J. , de Vries Elisabeth G.E. , Walch Axel , van Dam Gooitzen M. , Ntziachristos Vasilis 
Published: November 2016

Abstract
In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and nonmalignant tissues are usually distinguished on fluorescence images by applying empirically determined fluorescence intensity thresholds. Here, we report the development of fSTREAM, a set of analytic methods designed to streamline the analysis of surgically excised breast tissues by collecting and statistically processing hybrid multiscale fluorescence, color, and histology readouts toward precision fluorescence imaging. fSTREAM addresses core questions of how to relate fluorescence intensity to tumor tissue and how to quantitatively assign a normalized threshold that sufficiently differentiates tumor tissue from healthy tissue. Using fSTREAM we assessed human breast tumors stained in vivo with fluorescent bevacizumab at microdose levels. Showing that detection of such levels is achievable, we validated fSTREAM for high-resolution mapping of the spatial pattern of labeled antibody and its relation to the underlying cancer pathophysiology and tumor border on a per patient basis. We demonstrated a 98% sensitivity and 79% specificity when using labeled bevacizumab to outline the tumor mass. Overall, our results illustrate a quantitative approach to relate fluorescence signals to malignant tissues and improve the theranostic application of fluorescence molecular imaging. Cancer Res; 77(3); 623–31. ©2016 AACR.
High-Density Lipoprotein–Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1
Authors: Ruiz Mario , Frej Cecilia , Holmér Andreas , Guo Li J. , Tran Sinh , Dahlbäck Björn 
Published: November 2016

Objective—
Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P. The goal of this study is to elucidate the role of ApoM and S1P in endothelial anti-inflammatory events related to HDL.

Approach and Results—
Aortic or brain human primary endothelial cells were challenged with tumor necrosis factor-α (TNF-α) as inflammatory stimuli. The presence of recombinant ApoM-bound S1P or ApoM-containing HDL reduced the abundance of adhesion molecules in the cell surface, whereas ApoM and ApoM-lacking HDL did not. Specifically, ApoM-bound S1P decreased vascular adhesion molecule-1 (VCAM-1) and E-selectin surface abundance but not intercellular adhesion molecule-1. Albumin, which is an alternative S1P carrier, was less efficient in inhibiting VCAM-1 than ApoM-bound S1P. The activation of the S1P receptor 1 was sufficient and required to promote anti-inflammation. Moreover, ApoM-bound S1P induced the rearrangement of the expression of S1P-related genes to counteract TNF-α. Functionally, HDL/ApoM/S1P limited monocyte adhesion to the endothelium and maintained endothelial barrier integrity under inflammatory conditions.

Conclusions—
ApoM-bound S1P is a key component of HDL and is responsible for several HDL-associated protective functions in the endothelium, including regulation of adhesion molecule abundance, leukocyte-endothelial adhesion, and endothelial barrier.
Association of Bystander Cardiopulmonary Resuscitation and Survival According to Ambulance Response Times After Out-of-Hospital Cardiac Arrest
Authors: Rajan Shahzleen , Wissenberg Mads , Folke Fredrik , Hansen Steen Møller , Gerds Thomas A. , Kragholm Kristian , Hansen Carolina Malta , Karlsson Lena , Lippert Freddy K. , Køber Lars , Gislason Gunnar H. , Torp-Pedersen Christian 
Published: November 2016

Background:
Bystander-initiated cardiopulmonary resuscitation (CPR) increases patient survival after out-of-hospital cardiac arrest, but it is unknown to what degree bystander CPR remains positively associated with survival with increasing time to potential defibrillation. The main objective was to examine the association of bystander CPR with survival as time to advanced treatment increases.

Methods:
We studied 7623 out-of-hospital cardiac arrest patients between 2005 and 2011, identified through the nationwide Danish Cardiac Arrest Registry. Multiple logistic regression analysis was used to examine the association between time from 911 call to emergency medical service arrival (response time) and survival according to whether bystander CPR was provided (yes or no). Reported are 30-day survival chances with 95% bootstrap confidence intervals.

Results:
With increasing response times, adjusted 30-day survival chances decreased for both patients with bystander CPR and those without. However, the contrast between the survival chances of patients with versus without bystander CPR increased over time: within 5 minutes, 30-day survival was 14.5% (95% confidence interval [CI]: 12.8–16.4) versus 6.3% (95% CI: 5.1–7.6), corresponding to 2.3 times higher chances of survival associated with bystander CPR; within 10 minutes, 30-day survival chances were 6.7% (95% CI: 5.4–8.1) versus 2.2% (95% CI: 1.5–3.1), corresponding to 3.0 times higher chances of 30-day survival associated with bystander CPR. The contrast in 30-day survival became statistically insignificant when response time was >13 minutes (bystander CPR vs no bystander CPR: 3.7% [95% CI: 2.2–5.4] vs 1.5% [95% CI: 0.6–2.7]), but 30-day survival was still 2.5 times higher associated with bystander CPR. Based on the model and Danish out-of-hospital cardiac arrest statistics, an additional 233 patients could potentially be saved annually if response time was reduced from 10 to 5 minutes and 119 patients if response time was reduced from 7 (the median response time in this study) to 5 minutes.

Conclusions:
The absolute survival associated with bystander CPR declined rapidly with time. Yet bystander CPR while waiting for an ambulance was associated with a more than doubling of 30-day survival even in case of long ambulance response time. Decreasing ambulance response time by even a few minutes could potentially lead to many additional lives saved every year.
Abnormality in hippocampal signal intensity predicts atrophy in patients with systemic lupus erythematosus
Authors: Lapa A T , Pedro T , Francischinelli J , Coan A C , Costallat L T Lavras , Cendes F , Appenzeller S 
Published: November 2016

Objectives To quantify signal abnormalities in the hippocampus (Hsig) of patients with systemic lupus erythematosus (SLE) and to determine if Hsig predict hippocampal atrophy (HA) in SLE. Methods We included all SLE patients and healthy age- and sex-matched individuals with two magnetic resonance imaging (MRI) scans performed with a minimum of 1 year interval. All individuals underwent a standardized neuropsychological evaluation. Individual results were converted into standard scores and compared to normative data. SLE patients were additionally assessed for disease activity (SLE Disease Activity Index (SLEDAI)), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)), and the presence of antiphospholipid antibodies. MRI was performed on an Elscint 2 T scanner and T1 inversion recovery and T2 coronal images were used for analysis. Volumetric (HV) and signal quantification (Hsig) were determined by standardized protocols. Results We included 54 SLE patients (48 women; mean age 32.2 ± 10.56 years). Hsig were found at study entry in 15 (45.5%) patients. Hsig in the body and tail of non-atrophic hippocampi correlated with progression of volume loss during the follow-up period ( r = 0.8, p < 0.001). The presence of Hsig in the head of atrophic hippocampi correlated with progression of HA ( r = 0.73, p = 0.005) during the same period. No correlation of Hsig and disease activity or prednisone dose was observed. Conclusion HA is frequently observed in SLE patients and volume loss is progressive in a subgroup of patients. The evaluation of Hsig is an easy tool to determine patients that may have progressive hippocampal volume loss and should be followed more closely with MRI and cognitive evaluation.