bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
Authors: Doorenweerd Nathalie , Mahfouz Ahmed , van Putten Maaike , Kaliyaperumal Rajaram , t’ Hoen Peter A. C. , Hendriksen Jos G. M. , Aartsma-Rus Annemieke M. , Verschuuren Jan J. G. M. , Niks Erik H. , Reinders Marcel J. T. , Kan Hermien E. , Lelieveldt Boudewijn P. F. 
Published: September 2017

AbstractDuchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.
Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine
Authors: Hu Xiajun , Deng Yihuan , Chen Xiao , Zhou Yanzhao , Zhang Hongrong , Wu Hailang , Yang Shijun , Chen Fen , Zhou Zihua , Wang Min , Qiu Zhihua , Liao Yuhua 
Published: September 2017

AbstractWe developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.
Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity
Authors: Di Giacomo Simone , Sollazzo Manuela , de Biase Dario , Ragazzi Moira , Bellosta Paola , Pession Annalisa , Grifoni Daniela 
Published: September 2017

AbstractMYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development fromDrosophilato mammals. Cells expressing low levels of MYC, calledlosers, are committed to die by nearby cells with high MYC activity, calledwinners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC’s consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours.
Intermediate and low abundant protein analysis of vitamin D deficient obese and non-obese subjects by MALDI-profiling
Authors: Al-Daghri Nasser M. , Torretta Enrica , Capitanio Daniele , Fania Chiara , Guerini Franca Rosa , Sabico Shaun B. , Clerici Mario , Gelfi Cecilia 
Published: September 2017

AbstractObesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D deficiency and pathological levels of triglycerides, high-density lipoprotein cholesterol and high total cholesterol levels. The serum protein profiles of 64 vitamin D deficient (serum 25(OH)D < 50nmol/L) individuals with metabolic syndrome and with (n = 31; BMI ≥ 30) or without (n = 33; BMI < 30) obesity were analyzed by a quantitative label-free mass spectrometry approach (MALDI-profiling), combined with different serum immunodepletion strategies (Human7 and Human14 immuno-chromatographies), to analyze the intermediate- and low-abundant protein components. The analysis of intermediate-abundant proteins (Human7) in obese vs. non-obese subjects identified 14 changed peaks (p < 0.05) in the m/z range 1500–35000. Furthermore, the Human14 depletion provided new profiles related to obesity (121 changed peaks). Among changed peaks, 11 were identified in the m/z range 1500–4000 Da by high-resolution tandem mass spectrometry, belonging to apolipoprotein CIII, apolipoprotein B100, alpha-1-antichymotrypsin and complement C3. Data herein show that distinct protein profiles identify specific peptides belonging to lipid metabolism and inflammation processes that are associated with obesity and vitamin D deficiency.
Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging
Authors: Tsubata Yukari , Hayashi Mitsuhiro , Tanino Ryosuke , Aikawa Hiroaki , Ohuchi Mayu , Tamura Kenji , Fujiwara Yasuhiro , Isobe Takeshi , Hamada Akinobu 
Published: September 2017

AbstractAlthough drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to its ability to provide a comprehensive assessment of drug tissue distribution. Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor; however, it is unclear how this drug is histologically distributed in lung cancer. We used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze erlotinib distribution in the tumor and normal lung tissues of a mouse xenograft model and patient with non-small cell lung cancer. LC-MS/MS showed that the erlotinib tissue concentration in the xenograft tumor tissue was clearly lower than that in the normal tissue at the time of maximum blood concentration. MALDI-MSI showed the heterogeneous distribution of erlotinib at various levels in the murine tissues; interestingly, erlotinib was predominantly localized in the area of viable tumor compared to the necrotic area. In the patient-derived tissue, MALDI-MSI showed that there were different concentrations of erlotinib distributed within the same tissue. For drug development and translational research, the imaging pharmacokinetic study used the combination of MALDI-MSI and LC-MS/MS analyses may be useful in tissues with heterogeneous drug distribution.
Ultra-sensitive graphene sensor for measuring high vacuum pressure
Authors: Il Ahn Sung , Ra Jung Ju , Young Choi So , Hwa Son Min , Jin Hong Yu , Park Jung-Chul 
Published: September 2017

AbstractWe demonstrate here that several different graphene nanoribbon (GNR) samples can be separated from the GNR mixture synthesized by conventional methods. The sheet resistance of the purified GNR gradually decreased with decreasing pressure at 30 °C, whereas it increased at 100 °C. A hypothesis based on van der Waals attractive interactions between GNR sheets was introduced to explain this finding. This hypothesis verified by the shifted main peaks in vacuum X-ray diffraction spectra: 0.022 nm and 0.041 nm shifts were observed for reduced graphene oxide (RGO) and GNR, respectively. Theoretical calculations indicated that, for RGO, the shifted distance was similar to the calculated distance. The response of the GNR sensor to pressure changes occurred rapidly (in seconds). The normalized response time of each sample indicated that sensor using GNR reduced the tailing of the response time by shortening the diffusion path of gas molecules. The sensitivity of the GNR sensor was three times that of RGO in the given pressure range. Moreover, the sensitivity of GNR was much larger than those of the most popularly studied pressure sensors using Piezoresistivity, and the sensor could detect vacuum pressures of 8 × 10–7 Torr.
Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice
Authors: Zhang Peng , Li Guang , Li Hui , Tan XiaoQiu , Cheng Hai-Ying Mary 
Published: September 2017

AbstractIt remains unknown whether chronic circadian disturbance (CCD) during pregnancy can lead to mood disorders in the offspring. Here we show that pregnant mice in the F0 generation that were exposed to CCD stress displayed depression-like behaviors, and produced offspring in the F1 and F2 generations that also exhibited mood-associated behavioral phenotypes despite the lack of direct stressful experiences during their postnatal or adult period. Prenatal CCD stress was correlated with the elevation of plasma corticosterone levels in F1 mice. Furthermore, the diurnal expression profiles of core circadian clock genes were disrupted in the suprachiasmatic nucleus of F1 mice. Proteomics analysis revealed that prenatal CCD stress resulted in distinct changes in protein expression in the hypothalamus of female F1 mice, in particular proteins that were associated with cellular activities, metabolism, development and diseases. Sex-specific differences in melanocortin 4 receptor expression were apparent in the CCD F1 generation. We conclude that maternal exposure to chronic circadian disturbance during pregnancy can lead to sex-specific mood disorders that persist for at least two filial generations. The underlying mechanisms may depend on transgenerational changes in plasma corticosterone levels, circadian pacemaking, and hypothalamic protein expression.
Serum Zinc Status and Its Association with Allergic Sensitization: The Fifth Korea National Health and Nutrition Examination Survey
Authors: Seo Hyun-Min , Kim Yeong Ho , Lee Ji Hyun , Kim Joung Soo , Park Young Min , Lee Jun Young 
Published: September 2017

AbstractZinc (Zn) is an essential trace element that plays important roles in the immune system. There is little known about the role of trace elements in allergic diseases, and previous reports have shown conflicting results. The aim of this study was to investigate the relationship between serum Zn levels and total or allergen-specific immunoglobulin E (IgE) levels. The initial candidates for this study were those who participated in the 5th Korean National Health and Nutrition Examination Survey 2010 (n = 8,958), and 1,867 adults who had serum total and allergen specific-IgE levels measured were included. Upon adjusting for covariates, mean total IgE, Dermatophagoides farinae and dog-specific IgE levels increased significantly as the Zn levels decrease from the highest to the lowest quartile (p = 0.009, 0.004, and < 0.001, respectively). The multiple logistic regression analyses showed significant negative linear correlations between serum Zn levels and total, D. farinae-, cockroach-, and dog-specific IgE levels (p-value for linear trend = 0.004, 0.006, 0.027, and < 0.001, respectively). This study demonstrated that total/allergen specific IgE and Zn levels are significantly inversely related.
Exogenous auxin represses soybean seed germination through decreasing the gibberellin/abscisic acid (GA/ABA) ratio
Authors: Shuai Haiwei , Meng Yongjie , Luo Xiaofeng , Chen Feng , Zhou Wenguan , Dai Yujia , Qi Ying , Du Junbo , Yang Feng , Liu Jiang , Yang Wenyu , Shu Kai 
Published: September 2017

AbstractAuxin is an important phytohormone which mediates diverse development processes in plants. Published research has demonstrated that auxin induces seed dormancy. However, the precise mechanisms underlying the effect of auxin on seed germination need further investigation, especially the relationship between auxins and both abscisic acid (ABA) and gibberellins (GAs), the latter two phytohormones being the key regulators of seed germination. Here we report that exogenous auxin treatment represses soybean seed germination by enhancing ABA biosynthesis, while impairing GA biogenesis, and finally decreasing GA1/ABA and GA4/ABA ratios. Microscope observation showed that auxin treatment delayed rupture of the soybean seed coat and radicle protrusion. qPCR assay revealed that transcription of the genes involved in ABA biosynthetic pathway was up-regulated by application of auxin, while expression of genes involved in GA biosynthetic pathway was down-regulated. Accordingly, further phytohormone quantification shows that auxin significantly increased ABA content, whereas the active GA1 and GA4 levels were decreased, resulting insignificant decreases in the ratiosGA1/ABA and GA4/ABA.Consistent with this, ABA biosynthesis inhibitor fluridone reversed the delayed-germination phenotype associated with auxin treatment, while paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Altogether, exogenous auxin represses soybean seed germination by mediating ABA and GA biosynthesis.
IL-10-1082 A&gt;G (rs1800896) polymorphism confers susceptibility to pulmonary tuberculosis in Caucasians but not in Asians and Africans: a meta-analysis
Authors: Areeshi Mohammed Y. , Mandal Raju K. , Dar Sajad A. , Jawed Arshad , Wahid Mohd , Lohani Mohtashim , Panda Aditya K. , Mishra Bhartendu N. , Akhter Naseem , Haque Shafiul 
Published: September 2017

Background: Earlier studies have shown that interlukin-10 (IL-10) -1082 A&gt;G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A&gt;G gene polymorphism and PTB susceptibility.Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models.Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous (GG vs. AA: P=0.889; OR = 1.029, 95% CI = 0.692–1.529), heterozygous (GA vs. AA: P=0.244; OR = 0.906, 95% CI = 0.767–1.070), dominant (GG + AG vs. AA: P=0.357; OR = 1.196, 95% CI = 0.817–1.752), and recessive (GG vs. AA + AG: P=0.364; OR = 0.921, 95% CI = 0.771–1.100) genetic models. Likewise, no association of IL-10 -1082 A&gt;G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P=0.004; OR = 1.694, 95% CI = 1.183–2.425) demonstrated increased risk of PTB in Caucasian population.Conclusions: This meta-analysis concludes that IL-10 -1082 A&gt;G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population.
DBR‐free semiconductor disc laser on SiC heatspreader emitting 10.1 W at 1007 nm
Authors: Mirkhanov S. , Quarterman A.H. , Kahle H. , Bek R. , Pecoroni R. , Smyth C.J.C. , Vollmer S. , Swift S. , Michler P. , Jetter M. , Wilcox K.G. 
Published: September 2017

We report a distributed Bragg reflector‐free semiconductor disc laser which emits 10 W continuous wave output power at a wavelength of 1007 nm when pumped with 40 W at 808 nm, focused into a 230 μm diameter spot on the gain chip. By introducing a birefringent filter plate in the laser cavity the wavelength could be tuned from 995 to 1020 nm. The laser consisted of a gain chip located at the beam waist of a linear concentric resonator with an output coupling of 2.15%. The gain chip consists of a 1.574‐μm‐thick resonant periodic gain structure, with ten In0.13Ga0.87As quantum wells embedded in strain‐compensating GaAs0.94P0.06 barrier layers, van der Waals bonded to a silicon carbide intra‐cavity heat spreader.
Wireless energy‐harvesting circuit and system with error‐correction ASK demodulator for body sensor network with ultra‐high‐frequency RFID healthcare system
Authors: Lee Shuenn‐Yuh , Chen Tsung‐Yen , Tsou Chieh , Chu Yuan‐Sun 
Published: September 2017

This study presents a low‐power energy‐harvesting circuit with error‐correction demodulation for body sensor networks with radio‐frequency identification (RFID) systems. The proposed circuit adopts a new structure that facilitates the demodulation of amplitude‐shift‐keying (ASK) signals, and it includes a power unit consisting of a wake‐up circuit and a power‐on‐reset control circuit. The wireless bio‐signal acquisition system and the digital processor are implemented on a field‐programmable gate array to demonstrate the proposed RFID tag. The proposed energy‐harvesting circuit can substantially decrease the capacitance used by the demodulator circuit and the wake‐up circuit to as low as 14 pF. Moreover, a detection circuit and a correcting circuit are utilised to reduce the bit error rate of decoding. The wireless bio‐signal acquisition scenario is also set up and the communication signal between reader and tag is measured to demonstrate the system that can be employed in body sensor network with the healthcare system. The chip was implemented in complementary metal–oxide–semiconductor 0.18 μm technology. The sensitivity of this work is − 13 dBm. The pulse width error can be reduced to <1% by the error‐correction demodulator to fit the EPC Gen‐2 standard.
Prostaglandin E1 Protects the Peripheral Nerve in Diabetics through Preventing Vascular Permeability Changes
Authors: Mo Feifei , Hu Guotao , Liu Wei , He Li , Wang Hailan 
Published: September 2017

Abstract
Objective The aims of this study were to investigate the effects of the vasodilator prostaglandin E1 on microvascular permeability, the expression of vascular endothelial growth factor (VEGF), as well as the structural and functional changes of the peripheral nerve in diabetic rats.
Methods Streptozotocin-induced diabetes mellitus were randomly divided into two groups and intraperitoneally received, once daily, an injection of prostaglandin E1 at 1.6 μg/kg in normal saline or the same volume of normal saline (diabetic control), respectively. Six rats were randomly selected as normal controls.
Results Diabetic controls exhibited a significant increase in the tail flick threshold temperature, water content of the sciatic nerve, serum VEGF level, and VEGF level in the sciatic nerve; in addition, a decrease in the sciatic nerve conduction velocity (NCV) was observed, compared with normal rats (P<0.01). Treatment with prostaglandin E1 resulted in similar changes but at a slower rate than in those without treatment. Diabetic control rats also showed histological and ultrastructural abnormalities of the sciatic nerve, whereas prostaglandin E1-treated rats exhibited similar but less severe injury. The serum VEGF level was negatively correlated with the sciatic NCV (r=−0.932, P<0.01) and positively correlated with the tail flick threshold temperature (r=0.835, P<0.01) as well as the water content of the sciatic nerve (r=0.901, P<0.01).
Conclusion Prostaglandin E1 could protect the peripheral nerve by improving sciatic nerve function, reducing the VEGF level, and decreasing the vascular permeability. This study provides an experimental proof that prostaglandin E1 has potential benefits in improving DPN in early stage.
Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome
Authors: Hermanns Pia , Kumorowicz-Czoch Małgorzata , Grasberger Helmut , Refetoff Samuel , Pohlenz Joachim 
Published: September 2017

Abstract
Objective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome.
Design, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-binding capability and the transcriptional activity of the two mutated transcription factors were investigated in vitro.
Results The NKX2.1 mutation did not show any transcriptional activity and had almost no DNA-binding. The PAX8 mutation was normally located to the nucleus and showed a normal transactivation and a normal binding to the known downstream targets.
Conclusions The molecular defect explaining the phenotype of brain-lung-thyroid syndrome was identified. To what extent the PAX8 mutation contributes to the phenotype needs to be further investigated. We recommend to screen patients with CH and TD for mutations in all known TD candidate genes.
The Changes, or Plus ça change? Newburgh Hamilton's Early Writings and the Politics of Handel's Librettos
Authors: Stanyon Miranda 
Published: September 2017

ABSTRACTThis article examines the early writings of one of Handel's English librettists, Newburgh Hamilton. It describes what seems to be Hamilton's first publication, the little-studied Tory satire The Changes (1711), sets it alongside other early publications and biographical details, and reads this material alongside two of Hamilton's librettos for Handel, Alexander's Feast (1736) and Samson (1743). Hamilton's early writings are approached less as contexts for the oratorios than as texts with their own interest, and as intertexts to be set in dialogue with later productions. The article seeks to contribute to debate over the politics of Handel's vocal music, debate provoked not least by the difficulties of defining the sphere and meanings of politics in eighteenth-century culture, and of conceptualizing the collaborative endeavours and multiple sites of composition, patronage, business, performance and reception that make up Handel's oratorios.