bluuebunny/crossref_metadata_2025_split huggingface dataset:
Porcine NK cells display features associated with antigen-presenting cells
Authors: De Pelsmaeker Steffi , Devriendt Bert , Leclercq Georges , Favoreel Herman W 
Published: December 2017

Abstract
NK cells are members of the innate immunity and play a central role in the defense against viral infections and cancer development, but also contribute to triggering and shaping adaptive immune responses. Human NK cells may express MHC II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which allows them to stimulate the CD4+ T-cell response. In contrast, murine NK cells do not express MHC II or costimulatory molecules. Upon activation, mouse NK cells can acquire these molecules from dendritic cells (DCs) via intercellular membrane transfer, which leads to suppression of DC-induced CD4+ T-cell responses rather than stimulation of T-cell responses. Previous studies showed that porcine NK cells can express MHC II molecules, but it was unknown if porcine NK cells also express costimulatory molecules and whether NK cells may affect T-cell proliferation. We found that primary porcine NK cells express functional MHC II molecules and costimulatory CD80/86, particularly upon activation with IL-2/IL-12/IL-18, and that they are able to stimulate T-cell proliferation. In addition, we show that porcine NK cells are able to internalize antigens derived from killed target cells in an actin polymerization-dependent process. All together, these results indicate that porcine NK cells possess properties associated with APCs, which allows them to stimulate T-cell proliferation.
Bone marrow lesions in osteoarthritis: What lies beneath
Authors: Alliston Tamara , Hernandez Christopher J. , Findlay David M. , Felson David T. , Kennedy Oran D. 
Published: December 2017

ABSTRACTOsteoarthritis (OA) is the most common joint disease in the United States, affecting more than 30 million people, and is characterized by cartilage degeneration in articulating joints. OA can be viewed as a group of overlapping disorders, which result in functional joint failure. However, the precise cellular and molecular events within which lead to these clinically observable changes are neither well understood nor easily measurable. It is now clear that multiple factors, in multiple joint tissues, contribute to degeneration. Changes in subchondral bone are recognized as a hallmark of OA, but are normally associated with late‐stage disease when degeneration is well established. However, early changes such as Bone Marrow Lesions (BMLs) in OA are a relatively recent discovery. BMLs are patterns from magnetic resonance images (MRI) that have been linked with pain and cartilage degeneration. Their potential utility in predicting progression, or as a target for therapy, is not yet fully understood. Here, we will review the current state‐of‐the‐art in this field under three broad headings: (i) BMLs in symptomatic OA: malalignment, joint pain, and disease progression; (ii) biological considerations for bone‐cartilage crosstalk in joint disease; and (iii) mechanical factors that may underlie BMLs and drive their communication with other joint tissues. Thus, this review will provide insights on this topic from a clinical, biological, and mechanical perspective. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1818–1825, 2018.
A novel splice variant in EMC1 is associated with cerebellar atrophy, visual impairment, psychomotor retardation with epilepsy
Authors: Geetha Thenral S. , Lingappa Lokesh , Jain Abhishek Ravindra , Govindan Hridya , Mandloi Nitin , Murugan Sakthivel , Gupta Ravi , Vedam Ramprasad 
Published: December 2017

AbstractBackgroundSeveral genes have been implicated in a highly variable presentation of developmental delay with psychomotor retardation. Mutations in EMC1 gene have recently been reported. Herein, we describe a proband born of a consanguineous marriage, who presented with early infantile onset epilepsy, scaphocephaly, developmental delay, central hypotonia, muscle wasting, and severe cerebellar and brainstem atrophy.MethodsGenetic testing in the proband was performed using custom clinical exome and targeted next‐generation sequencing. This was followed by segregation analysis of the variant in the parents by Sanger sequencing and evaluation of the splice variant by RNA sequencing.ResultsClinical exome sequencing identified a novel homozygous intronic splice variant in the EMC1 gene (chr1:19564510C>T, c.1212 + 1G>A, NM_015047.2). Neither population databases (ExAC and 1000 genomes) nor our internal database (n = 1,500) had reported this rare variant, predicted to affect the splicing. RNA sequencing data from the proband confirmed aberrant splicing with intron 11 retention, thereby introducing a stop codon in the resultant mRNA. This nonsense mutation is predicted to result in the premature termination of protein synthesis leading to loss of function of the EMC1 protein.ConclusionWe report, for the first time the role of aberrant EMC1RNA splicing as a potential cause of disease pathogenesis. The severe epilepsy observed in our study expands the disease‐associated phenotype and also emphasizes the need for comprehensive screening of intronic splice mutations.
Vitamin A Deficiency Induces Autistic‐Like Behaviors in Rats by Regulating the RARβ‐CD38‐Oxytocin Axis in the Hypothalamus
Authors: Lai Xi , Wu Xiaofeng , Hou Nali , Liu Shu , Li Qing , Yang Ting , Miao Jingkun , Dong Zhifang , Chen Jie , Li Tingyu 
Published: December 2017

ScopeVitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic‐like behaviors via the transcription factor retinoic acid receptor beta (RARβ)‐regulated cluster of differentiation 38 (CD38)‐oxytocin (OXT) axis.Methods and resultsGestational VAD or VA supplementation (VAS) rat models are established, and the autistic‐like behaviors in the offspring rats are investigated. The different expression levels of RARβ and CD38 in hypothalamic tissue and serum retinol and OXT concentration are tested. Primary cultured rat hypothalamic neurons are treated with all‐trans retinoic acid (atRA), and recombinant adenoviruses carrying the rat RARβ (AdRARβ) or RNA interference virus RARβ‐siRNA (siRARβ) are used to infect neurons to change RARβ signal. Western blotting, chromatin immunoprecipitation (ChIP), and intracellular Ca2+ detections are used to investigate the primary regulatory mechanism of RARβ in the CD38‐OXT signaling pathway. We found that gestational VAD increases autistic‐like behaviors and decreases the expression levels of hypothalamic RARβ and CD38 and serum OXT levels in the offspring. VAS ameliorates these autistic‐like behaviors and increases the expression levels of RARβ, CD38, and OXT in the gestational VAD pups. In vitro, atRA increases the Ca2+ excitability of neurons, which might further promote the release of OXT. Different CD38 levels are induced in the neurons by infection with different RARβ adenoviruses. Furthermore, atRA enhances the binding of RARβ to the proximal promoter of CD38, indicating a potential upregulation of CD38 transcriptional activity by RARβ.ConclusionsGestational VAD might be a risk factor for autistic‐like behaviors due to the RARβ signal suppression of CD38 expression in the hypothalamus of the offspring, which improves with VAS during the early‐life period. The nutritional status during pregnancy and the early‐life period is important in rats.
Quantitative assessment of cerebral venous blood T2 in mouse at 11.7T: Implementation, optimization, and age effect
Authors: Wei Zhiliang , Xu Jiadi , Liu Peiying , Chen Lin , Li Wenbo , van Zijl Peter , Lu Hanzhang 
Published: December 2017

PurposeTo develop a non–contrast‐agent MRI technique to quantify cerebral venous T2 in mice.MethodsWe implemented and optimized a T2‐relaxation‐under‐spin‐tagging (TRUST) sequence on an 11.7 Tesla animal imaging system. A flow‐sensitive‐alternating‐inversion‐recovery (FAIR) module was used to generate control and label images, pair‐wise subtraction of which yielded blood signals. Then, a T2‐preparation module was applied to produce T2‐weighted images, from which blood T2 was quantified. We conducted a series of technical studies to optimize the imaging slice position, inversion slab thickness, post‐labeling delay (PLD), and repetition time. We also performed three physiological studies to examine the venous T2 dependence on hyperoxia (N = 4), anesthesia (N = 3), and brain aging (N = 5).ResultsOur technical studies suggested that, for efficient data acquisition with minimal bias in estimated T2, a preferred TRUST protocol was to place the imaging slice at the confluence of sagittal sinuses with an inversion‐slab thickness of 2.5‐mm, a PLD of 1000 ms and a repetition time of 3.5 s. Venous T2 values under normoxia and hyperoxia (inhaling pure oxygen) were 26.9 ± 1.7 and 32.3 ± 2.2 ms, respectively. Moreover, standard isoflurane anesthesia resulted in a higher venous T2 compared with dexmedetomidine anesthesia (N = 3; P = 0.01) which is more commonly used in animal functional MRI studies to preserve brain function. Venous T2 exhibited a decrease with age (N = 5; P < 0.001).ConclusionWe have developed and optimized a noninvasive method to quantify cerebral venous blood T2 in mouse at 11.7 T. This method may prove useful in studies of brain physiology and pathophysiology in animal models. Magn Reson Med 80:521–528, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Sedentary Time and MRI‐Derived Measures of Adiposity in Active Versus Inactive Individuals
Authors: Henson Joseph , Edwardson Charlotte L. , Morgan Bruno , Horsfield Mark A. , Khunti Kamlesh , Davies Melanie J. , Yates Thomas 
Published: December 2017

ObjectiveThe aim of this study was to examine cross‐sectional associations between objectively measured sedentary time and magnetic resonance imaging (MRI)‐assessed adiposity in a population at high risk for type 2 diabetes (T2DM) and to determine whether associations are modified by the recommended levels of moderate‐to‐vigorous physical activity (MVPA).MethodsSedentary time and MVPA were measured objectively by using accelerometers. Linear regression models examined the association of sedentary time with liver, visceral, subcutaneous, and total abdominal fat (quantified by using MRI). Interaction terms determined whether results were consistent across activity categories (active [> 150 min/wk of MVPA] vs. inactive [< 150 min/wk of MVPA]).ResultsOne hundred and twenty‐four participants (age = 64.0 ± 7.1 years; male = 65.3%; BMI = 31.8 ± 5.6 kg/m2) were included. Following adjustment, each 60 minutes of sedentary time was associated with 1.74 L higher total abdominal fat, 0.62 L higher visceral fat, 1.14 L higher subcutaneous fat, and 1.86% higher liver fat. When results were stratified by MVPA (active vs. inactive), sedentary time was associated with greater liver, visceral, and total abdominal fat in the inactive group only.ConclusionsThese findings suggest that sedentary time is associated with higher levels of inter‐ and intraorgan fat, but associations with liver, visceral, and total abdominal fat were stronger in those who do not reach the current exercise recommendations for health.
Extending the Scope of 19F Hyperpolarization through Signal Amplification by Reversible Exchange in MRI and NMR Spectroscopy
Authors: Olaru Alexandra M. , Robertson Thomas B. R. , Lewis Jennifer S. , Antony Alex , Iali Wissam , Mewis Ryan E. , Duckett Simon B. 
Published: December 2017

AbstractFluorinated ligands have a variety of uses in chemistry and industry, but it is their medical applications as 18F‐labelled positron emission tomography (PET) tracers where they are most visible. In this work, we illustrate the potential of using 19F‐containing ligands as future magnetic resonance imaging (MRI) contrast agents and as probes in magnetic resonance spectroscopy studies by significantly increasing their magnetic resonance detectability through the signal amplification by reversible exchange (SABRE) hyperpolarization method. We achieve 19F SABRE polarization in a wide range of molecules, including those essential to medication, and analyze how their steric bulk, the substrate loading, polarization transfer field, pH, and rate of ligand exchange impact the efficiency of SABRE. We conclude by presenting 19F MRI results in phantoms, which demonstrate that many of these agents show great promise as future 19F MRI contrast agents for diagnostic investigations.
Imatinib resistance was reversed by nilotinib in the acute transformation of chronic myeloid leukemia: A case report
Authors: Xiao Meng , Zhou Hongjing , Li Shuguo , Xin Chunlei , Zhao Tongfeng , Hao Yunliang , Li Shumei , Liang Yanyan 
Published: December 2017

AbstractChronic myeloid leukemia (CML) is a clonal malignant hematopoietic disorder that arises in a hematopoietic stem cell. Its characteristic cytogenetic abnormality is an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. The BCR‐ABL1 fusion gene in this chromosome can encode a tyrosine protein kinase and is the molecular basis of CML pathogenesis. The tyrosine kinase inhibitor (TKI) imatinib is the ‘gold standard’ therapy for the treatment of CML. However, around 30% of the patients develop imatinib resistance. In this report, we will illustrate a case of an adult female with acute transformation of CML whose imatinib resistance was reversed by nilotinib and has had a long‐term survival.
Role of postmastectomy radiation therapy in breast cancer patients with different pathological responses to neoadjuvant chemotherapy
Authors: Guo Huan , Kong Lingling , Xing Ligang 
Published: December 2017

AbstractObjectiveThe purpose of the present study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy in breast cancer patients of clinical stage II–III with different pathological responses to neoadjuvant chemotherapy.MethodsWe retrospectively analyzed 79 clinical stage II–III breast cancer patients who underwent mastectomy after neoadjuvant chemotherapy between 2008 and 2013. According to the Miller–Payne grading system, we defined grades 1–2 as the poor response group, and grades 3–5 as the good response group. The 5‐year curves for locoregional recurrence free survival (LRRFS), distant disease‐free survival, and overall survival were constructed using the Kaplan–Meier method, and compared using the log–rank test.ResultsFor all patients, the median age was 48 years (range 29–68 years). At a median follow up of 56 months, the 5‐year LRRFS was 97.8% and 81.8% (P = 0.01), the 5‐year distant disease‐free survival was 73.9% and 75.8% (P = 0.14), and the 5‐year overall survival for both was 84.8% (P = 0.96). In the subgroup analysis, the LRRFS, distant disease‐free survival, and overall survival of the subgroup with a good response did not benefit from PMRT. However, the LRRFS of the poor response subgroup can significantly benefit from PMRT (P = 0.04).ConclusionsPMRT was effective in reducing the local‐regional recurrence rate for patients with a Miller–Payne grade 1–2; therefore, we suggest that PMRT should be considered for these patients.
Combined treatment with a selective PDE10A inhibitor TAK‐063 and either haloperidol or olanzapine at subeffective doses produces potent antipsychotic‐like effects without affecting plasma prolactin levels and cataleptic responses in rodents
Authors: Suzuki Kazunori , Harada Akina , Suzuki Hirobumi , Capuani Clizia , Ugolini Annarosa , Corsi Mauro , Kimura Haruhide 
Published: December 2017

AbstractActivation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D2 receptor antagonism. TAK‐063 [1‐[2‐fluoro‐4‐(1H‐pyrazol‐1‐yl)phenyl]‐5‐methoxy‐3‐(1‐phenyl‐1H‐pyrazol‐5‐yl)pyridazin‐4(1H)‐one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs through increasing both cAMP and cGMP levels by inhibition of their degradation. The activation of indirect pathway MSNs through the distinct mechanism of action of these drugs raises the possibility of augmented pharmacological effects by combination therapy. In this study, we evaluated the potential of combination therapy with TAK‐063 and current antipsychotics, such as haloperidol or olanzapine after oral administration. Combined treatment with TAK‐063 and either haloperidol or olanzapine produced a significant increase in phosphorylation of glutamate receptor subunit 1 in the rat striatum. An electrophysiological study using rat corticostriatal slices showed that TAK‐063 enhanced N‐methyl‐D‐aspartic acid receptor‐mediated synaptic responses in both direct and indirect pathway MSNs to a similar extent. Further evaluation using pathway‐specific markers revealed that coadministration of TAK‐063 with haloperidol or olanzapine additively activated the indirect pathway, but not the direct pathway. Combined treatment with TAK‐063 and either haloperidol or olanzapine at subeffective doses produced significant effects on methamphetamine‐ or MK‐801‐induced hyperactivity in rats and MK‐801‐induced deficits in prepulse inhibition in mice. TAK‐063 at 0.1 mg/kg did not affect plasma prolactin levels and cataleptic response from antipsychotics in rats. Thus, TAK‐063 may produce augmented antipsychotic‐like activities in combination with antipsychotics without effects on plasma prolactin levels and cataleptic responses in rodents.
Natriuretic peptide receptor‐C‐mediated attenuation of vascular smooth muscle cell hypertrophy involves Gqα/PLCβ1 proteins and ROS‐associated signaling
Authors: Jain Ashish , Anand‐Srivastava Madhu B. 
Published: December 2017

AbstractHypertension is associated with vascular remodeling due to hyperproliferation and hypertrophy of vascular smooth muscle cells (VSMC). Recently, we showed the implication of enhanced expression of Gqα and PLCβ1 proteins in hypertrophy of VSMCs from 16‐week‐old spontaneously hypertensive rats (SHR). The aim of this study was to investigate whether C‐ANP4‐23, a natriuretic peptide receptor‐C (NPR‐C) ligand that was shown to inhibit vasoactive peptide‐induced enhanced protein synthesis in A10 VSMC could also attenuate hypertrophy of VSMC isolated from rat model of cardiac hypertrophy and to further explore the possible involvement of Gqα/PLCβ1 proteins and ROS‐mediated signaling in this effect. The protein synthesis and cell volume, markers of hypertrophy were significantly enhanced in VSMC from 16‐week‐old SHR compared with age‐matched WKY rats and C‐ANP4‐23 treatment attenuated both to WKY levels. In addition, C‐ANP4‐23 treatment also attenuated the enhanced expression of AT1 receptor, Gqα, PLCβ1, Nox4, and p47phox proteins, the enhanced activation of EGFR, PDGFR, IGF‐1R, enhanced phosphorylation of ERK1/2/AKT and c‐Src in VSMC from SHR. Furthermore, the enhanced levels of superoxide anion and NADPH oxidase activity exhibited by VSMC from SHR were also attenuated to control levels by C‐ANP4‐23 treatment. These results indicate that C‐ANP4‐23 via the activation of NPR‐C attenuates VSMC hypertrophy through decreasing the overexpression of Gqα/PLCβ1 proteins, enhanced oxidative stress, increased activation of growth factor receptors, and enhanced phosphorylation of MAPK/AKT signaling pathways. Thus, it can be suggested that C‐ANP4‐23 may be used as a therapeutic agent for the treatment of vascular complications associated with hypertension and atherosclerosis.
A Schiff Base Macrocycle Ligand and Its Mg(II) and Cd(II) Complexes: Spectral Properties with Theoretical Understanding and Biological Activity
Authors: Halder Arijit , Mazumdar Swagata , Das Anamika , Karmakar Parimal , Ghoshal Debajyoti 
Published: December 2017

AbstractSimple Schiff base condensation is employed to prepare a macrocyclic ligand (L1H4) with a support of intramolecular hydrogen templating effect. Reaction with Mg(II) and Cd(II) a total number of three complexes namely, [L14–(Mg2+)2] (1), [L14–(Cd2+)2(H2O)2] (2) and [H2L12–Cd2+] (3) is obtained under same reaction condition and same solvent. Ligand and the complexes are identified and characterized by different spectroscopic techniques. Further the structural geometry and absorption spectra were analyzed by DFT (for ligand)/ semi‐empherical method (for complexes). Considering the involvement of metal ions in the regulation of cell proliferation we further explored the effect of these macrocycle confined metal complexes on human skin fibroblast cell line (GM00637) with or without the presence of fibroblasts stimulant (extracts fromCalendula officinalisandMorinda citrifolia). Also, same study has been performed with ligand and metal ion without mixing them. Among these Cd(II) complexes are found most promising. Luminescent property for the ligand and all the complexes are also examined and analyzed theoretically.
Catalytic Hydrotreatment of Jatropha Oil over Lanthanum Hydroxide Supported Noble Metals: Effect of Promotion with Cerium
Authors: Patil Shailesh J. , Vaidya Prakash D. 
Published: December 2017

AbstractCatalytic hydrotreatment of jatropha oil is an attractive option for the production of diesel‐range hydrocarbons. Here, we synthesized and tested the performance of two novel La(OH)3 supported Pd and Ru catalysts promoted with Ce, viz. Pd−Ce/La(OH)3 and Ru−Ce/La(OH)3 (hereafter referred to as Pd−Ce and Ru−Ce). The deoxygenation of jatropha oil was performed in a fixed‐bed reactor. The reaction conditions were varied so: temperature 603 to 663 K, weight hourly space velocity (WHSV) 1 to 4 h−1, pressure 1.5 to 3 MPa and H2/oil ratio 200 to 1000 (v/v). The performance of our lab‐made materials was encouraging. Upon optimization of the hydrotreating process, the best performance of both Pd‐Ce and Ru−Ce was achieved at T=663 K, WHSV=1 h−1, P=3 MPa and H2/oil ratio=600 v/v. Oil conversion at these reaction conditions was 97.3 and 91.8% over Pd−Ce and Ru−Ce. The respective hydrocarbon yield was 81% (for Pd−Ce) and 75.3% (for Ru−Ce). The resilience of the lab‐made catalysts was tested by time‐on‐stream study. Both catalysts were stable for 40 hours of time‐on‐stream. Finally, reaction pathway for deoxygenation of triglycerides over the investigated catalysts was proposed.
Adsorption Behaviors of Rubidium and Cesium Ions from Aqueous Solution onto Sodium Tetraphenylborate ‐ Polyacrylonitrile (TPB‐PAN)
Authors: Bao Amin , Zheng Hong , Liu Zeyu , Huang Dongfang 
Published: December 2017

AbstractIn this study, a novel composite adsorbent of sodium tetraphenylborate – polyacrylonitrile (TPB–PAN) was prepared for investigating adsorption behaviors of rubidium (Rb) and cesium (Cs) ions from their aqueous solutions. Several experimental parameters such as pH, shaking time, initial concentration, and interference ions were routinely evaluated. The experimental results showed that the Rb(I) and Cs(I) were both adsorbed by the adsorbent of TPB‐PAN at pH 7.0, and the adsorption equilibriums were achieved within 2 h. The presence of co‐existing ions did not get involved with Rb(I) and Cs(I) adsorption, indicating the high selectivity of TPB‐PAN adsorbent toward Rb(I) and Cs(I) ions. Under optimum conditions, the maximum adsorption capacities for Rb(I) and Cs(I) ions by the adsorbent of TPB‐PAN were 44.64 mg g−1and 118.48 mg g−1based on the langmuir sorption isotherm study. In addition, the adsorption processes of rubidium and cesium both are exothermic spontaneous process. Therefore, the proposed adsorbent of TPB‐PAN allowed the selective, sensitive, easy to use, cost‐effective, high efficiency, fast kinetics of preconcentration and separation (removal) Rb(I) and Cs(I) ions even in the presence of competing ions. As a consequence, the TPB‐PAN adsorbent can be used potentially for preconcentration and separation Rb(I) and Cs(I) ions from water samples in a wide range of practical applications for removal Rb(I) and Cs(I) ions in environmental aqueous resources.