bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Trefoil Factor 3 induces the transcription of its own promoter through STAT3
Authors: Sun Yong , Wang Liangxi , Zhou Yifang , Mao Xuefei , Deng Xiangdong 
Published: July 2016

AbstractHuman trefoil factor 3 (hTFF3) is a small peptide of potential therapeutic value. The mechanisms underlying the transcriptional regulation of hTFF3 remain unclear. The purpose of this study was to identify the core functional elements for the self-induction action of hTFF3 and transcription factors. First, truncated promoters were constructed to identify the functional regions of the hTFF3 promoter. Next, point mutation, chromatin immunoprecipitation, RNA interference and gene overexpression experiments were performed to analyze the transcriptional binding sites responsible for the self-induced transcription of hTFF3. Our results revealed the −1450 bp to −1400 bp fragment of the hTFF3 promoter was the functional region for the self-induction action of hTFF3. Bioinformatics analysis confirmed that a STAT3 binding site is present in the −1417 bp to −1409 bp region. Subsequently, site-directed mutagenesis analysis determined that this STAT3 binding site was critical for the self-induction effect of hTFF3. ChIP experiments confirmed that STAT3 binds to the hTFF3 promoter. STAT3 overexpression and knockdown experiments revealed that STAT3 enhanced the self-induction effect and the expression of hTFF3. This study confirmed that hTFF3 exhibits self-induction action, and that STAT3 is the key transcription factor to maintain the function of self-induction.
A small-angle X-ray scattering study of alpha-synuclein from human red blood cells
Authors: Araki Katsuya , Yagi Naoto , Nakatani Rie , Sekiguchi Hiroshi , So Masatomo , Yagi Hisashi , Ohta Noboru , Nagai Yoshitaka , Goto Yuji , Mochizuki Hideki 
Published: July 2016

Abstractα-synuclein (α-syn) is the main component of Lewy bodies, which are neuropathological hallmarks of patients with Parkinson’s disease. As it has been controversial whether human α-syn from erythrocytes exists as a tetramer under physiological conditions, we tried solving this issue by the small-angle X-ray solution scattering method. Under two different conditions (high ionic strength with a Tris buffer and low ionic strength with an ammonium acetate buffer), no evidence was found for the presence of tetramer. When comparing erythrocyte and recombinant α-syn molecules, we found no significant difference of the molecular weight and the secondary structure although the buffer conditions strongly affect the radius of gyration of the protein. The results indicate that, even though a stable tetramer may not be formed, conformation of α-syn depends much on its environment, which may be the reason for its tendency to aggregate in cells.
In-column ATR-FTIR spectroscopy to monitor affinity chromatography purification of monoclonal antibodies
Authors: Boulet-Audet Maxime , Kazarian Sergei G. , Byrne Bernadette 
Published: July 2016

AbstractIn recent years many monoclonal antibodies (mAb) have entered the biotherapeutics market, offering new treatments for chronic and life-threatening diseases. Protein A resin captures monoclonal antibody (mAb) effectively, but the binding capacity decays over repeated purification cycles. On an industrial scale, replacing fouled Protein A affinity chromatography resin accounts for a large proportion of the raw material cost. Cleaning-in-place (CIP) procedures were developed to extend Protein A resin lifespan, but chromatograms cannot reliably quantify any remaining contaminants over repeated cycles. To study resin fouling in situ, we coupled affinity chromatography and Fourier transform infrared (FTIR) spectroscopy for the first time, by embedding an attenuated total reflection (ATR) sensor inside a micro-scale column while measuring the UV 280 nm and conductivity. Our approach quantified the in-column protein concentration in the resin bed and determined protein conformation. Our results show that Protein A ligand leached during CIP. We also found that host cell proteins bound to the Protein A resin even more strongly than mAbs and that typical CIP conditions do not remove all fouling contaminants. The insights derived from in-column ATR-FTIR spectroscopic monitoring could contribute to mAb purification quality assurance as well as guide the development of more effective CIP conditions to optimise resin lifespan.
The Frequency and Energy of Snoring Sounds Are Associated with Common Carotid Artery Intima-Media Thickness in Obstructive Sleep Apnea Patients
Authors: Lee Guo-She , Lee Li-Ang , Wang Chao-Yung , Chen Ning-Hung , Fang Tuan-Jen , Huang Chung-Guei , Cheng Wen-Nuan , Li Hsueh-Yu 
Published: July 2016

AbstractObstructive sleep apnea (OSA) is a known risk factor for atherosclerosis. We investigated the association of common carotid artery intima-media thickness (CCA-IMT) with snoring sounds in OSA patients. A total of 30 newly diagnosed OSA patients with no history of cardiovascular diseases were prospectively enrolled for measuring mean CCA-IMT with B-mode ultrasonography, body mass index, metabolic syndrome, 10-year cardiovascular disease risk score, high-sensitivity C-reactive protein, and homocysteine. Good-quality signals of full-night snoring sounds in an ordinary sleep condition obtained from 15 participants were further acoustically analyzed (Included group). All variables of interest were not significantly different (all p > 0.05) between the included and non-included groups except for diastolic blood pressure (p = 0.037). In the included group, CCA-IMT was significantly correlated with snoring sound energies of 0–20 Hz (r = 0.608, p = 0.036) and 652–1500 Hz (r = 0.632, p = 0.027) and was not significantly associated with that of 20–652 Hz (r = 0.366, p = 0.242) after adjustment for age and sex. Our findings suggest that underlying snoring sounds may cause carotid wall thickening and support the large-scale evaluation of snoring sound characters as markers of surveillance and for risk stratification at diagnosis.
Molecular characterization of Tps1 and Treh genes in Drosophila and their role in body water homeostasis
Authors: Yoshida Miki , Matsuda Hiroko , Kubo Hitomi , Nishimura Takashi 
Published: July 2016

AbstractIn insects, trehalose serves as the main sugar component of haemolymph. Trehalose is also recognized as a mediator of desiccation survival due to its proposed ability to stabilize membranes and proteins. Although the physiological role of trehalose in insects has been documented for decades, genetic evidence to support the importance of trehalose metabolism remains incomplete. We here show on the basis of genetic and biochemical evidence that the trehalose synthesis enzyme Tps1 is solely responsible for the de novo synthesis of trehalose in Drosophila. Conversely, a lack of the gene for the trehalose hydrolyzing enzyme Treh causes an accumulation of trehalose that is lethal during the pupal period, as is observed with Tps1 mutants. Lack of either Tps1 or Treh results in a significant reduction in circulating glucose, suggesting that the maintenance of glucose levels requires a continuous turnover of trehalose. Furthermore, changes in trehalose levels are positively correlated with the haemolymph water volume. In addition, both Tps1 and Treh mutant larvae exhibit a high lethality after desiccation stress. These results demonstrate that the regulation of trehalose metabolism is essential for normal development, body water homeostasis, and desiccation tolerance in Drosophila.
Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome
Authors: Lee Li-Ang , Lo Yu-Lun , Yu Jen-Fang , Lee Gui-She , Ni Yung-Lun , Chen Ning-Hung , Fang Tuan-Jen , Huang Chung-Guei , Cheng Wen-Nuan , Li Hsueh-Yu 
Published: July 2016

AbstractSnoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and <10 events/hour) in patients with OSAHS. This prospective cohort study recruited 36 OSAHS patients for 6-hour snoring sound recordings during in-lab full-night polysomnography, drug-induced sleep endoscopy (DISE), and relocation pharyngoplasty. All patients received follow-up polysomnography after 6 months. Fifteen (42%) patients with at least two complete obstruction sites defined by DISE were significantly, positively associated with maximal snoring sound intensity (40–300 Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05–1.49) and body mass index (OR, 1.48, 95% CI 1.02–2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301–850 Hz; OR, 0.84, 95% CI 0.74–0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301–850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses.
Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels
Authors: Reni Carlotta , Mangialardi Giuseppe , Meloni Marco , Madeddu Paolo 
Published: July 2016

AbstractPatients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs. In vitro studies demonstrate the involvement of acidosis in OCL activation and the implication of transient receptor potential cation channel subfamily V member 1 (TRPV1). In vivo studies confirm the establishment of local acidosis in the diabetic bone marrow (BM) as well as the ineffectiveness of insulin in correcting the pH variation and osteoclast activation. Conversely, treatment with TRPV1 receptor antagonists re-establishes a physiological OCL availability. These data suggest that diabetes causes local acidosis in the BM that in turn increases osteoclast activation through the modulation of TRPV1. The use of clinically available TRPV1 antagonists may provide a new means to combat bone problems associated with diabetes.
Changes in perception of treatment efficacy are associated to the magnitude of the nocebo effect and to personality traits
Authors: Corsi Nicole , Emadi Andani Mehran , Tinazzi Michele , Fiorio Mirta 
Published: July 2016

AbstractThe nocebo effect in motor performance consists in a reduction of force and increase of fatigue following the application of an inert treatment that the recipient believes to be effective. This effect is variable across individuals and it is usually stronger if conditioning –exposure to the active effect of the treatment– precedes a test session, in which the treatment is inert. In the current explorative study we used a conditioning procedure to investigate whether subjective perception of treatment effectiveness changes between the conditioning and the test session and whether this change is related to dispositional traits and to the nocebo-induced reduction of force. Results showed that 56.1% of participants perceived the treatment as more effective in the test than in the conditioning session, had a more pronounced reduction of force, felt more effort and sense of weakness and were characterized by lower levels of optimism and higher anxiety traits compared to the other 43.9% of participants, who conversely perceived the treatment as less effective in the test session than in the conditioning. These findings highlight for the first time a link between changes in perception of treatment effectiveness, personality traits and the magnitude of the nocebo response in motor performance.
Verification of watershed vegetation restoration policies, arid China
Authors: Zhang Chengqi , Li Yu 
Published: July 2016

AbstractVerification of restoration policies that have been implemented is of significance to simultaneously reduce global environmental risks while also meeting economic development goals. This paper proposed a novel method according to the idea of multiple time scales to verify ecological restoration policies in the Shiyang River drainage basin, arid China. We integrated modern pollen transport characteristics of the entire basin and pollen records from 8 Holocene sedimentary sections and quantitatively reconstructed the millennial-scale changes of watershed vegetation zones by defining a new pollen-precipitation index. Meanwhile, Empirical Orthogonal Function method was used to quantitatively analyze spatial and temporal variations of Normalized Difference Vegetation Index in summer (June to August) of 2000–2014. By contrasting the vegetation changes that mainly controlled by millennial-scale natural ecological evolution with that under conditions of modern ecological restoration measures, we found that vegetation changes of the entire Shiyang River drainage basin are synchronous in both two time scales and the current ecological restoration policies met the requirements of long-term restoration objectives and showed promising early results on ecological environmental restoration. Our findings present an innovative method to verify river ecological restoration policies and also provide the scientific basis to propose future emphasizes of ecological restoration strategies.
cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness
Authors: Wiley Luke A. , Burnight Erin R. , DeLuca Adam P. , Anfinson Kristin R. , Cranston Cathryn M. , Kaalberg Emily E. , Penticoff Jessica A. , Affatigato Louisa M. , Mullins Robert F. , Stone Edwin M. , Tucker Budd A. 
Published: July 2016

AbstractImmunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans.
Chronic Repression of mTOR Complex 2 Induces Changes in the Gut Microbiota of Diet-induced Obese Mice
Authors: Jung Mi-Ja , Lee Jina , Shin Na-Ri , Kim Min-Soo , Hyun Dong-Wook , Yun Ji-Hyun , Kim Pil Soo , Whon Tae Woong , Bae Jin-Woo 
Published: July 2016

AbstractAlterations in the gut microbiota play a crucial role in host physiology and metabolism; however, the molecular pathways underlying these changes in diet-induced obesity are unclear. Mechanistic target of rapamycin (mTOR) signaling pathway is associated with metabolic disorders such as obesity and type 2 diabetes (T2D). Therefore, we examined whether changes in the regulation of mTOR signaling induced by diet (a high-fat diet [HFD] or normal-chow diet) and/or therapeutics (resveratrol [a specific inhibitor of mTOR complex 1] or rapamycin [an inhibitor of both mTOR complex 1 and 2]) altered the composition of the gut microbiota in mice. Oral administration of resveratrol prevented glucose intolerance and fat accumulation in HFD-fed mice, whereas rapamycin significantly impaired glucose tolerance and exacerbated intestinal inflammation. The abundance of Lactococcus, Clostridium XI, Oscillibacter, and Hydrogenoanaerobacterium increased under the HFD condition; however, the abundance of these species declined after resveratrol treatment. Conversely, the abundance of unclassified Marinilabiliaceae and Turicibacter decreased in response to a HFD or rapamycin. Taken together, these results demonstrated that changes in the composition of intestinal microbiota induced by changes in mTOR activity correlate with obese and diabetic phenotypes.
0.012 mm2 800 µW 0.1–6.4 GHz multi‐protocol PLL with 14 psrms integrated jitter in 28 nm FD‐SOI
Authors: Gupta N. , Lahiri A. , Kumar A. 
Published: July 2016

A multi‐protocol PLL suitable for different wireline standards namely HDMI1.4, USB2.0, DDR4, DisplayPort1.2 and for host clock generation for low‐power system‐on‐chips is presented. The PLL employs automatic VCO gain and charge‐pump current calibration circuits to provide a near constant PLL bandwidth which enables a robust jitter performance across process, voltage, temperature. Without increasing the loop‐filter capacitor, dual‐path loop‐filter technique is employed to reduce output jitter due to thermal noise of loop‐filter resistor. The PLL designed in 28 nm fully depleted silicon on insulator (FD‐SOI) process has an output frequency range from 0.1 to 6.4 GHz, total rms integrated jitter of 14 ps at 21.25 MHz reference frequency, consumes 800 µW at 3.4 GHz VCO frequency and occupies an area of 0.012 mm2.
Condition assessment of outdoor porcelain insulator based on dielectric dissipation factor evaluated from non‐linear equivalent circuit
Authors: Pradhan Arpan Kumar , Chatterjee Soumya , Banik Apu , Dalai Sovan , Chatterjee Biswendu 
Published: July 2016

This study presents a novel technique for estimation of contamination level as well as flashover voltage of outdoor insulators based on dielectric dissipation factor evaluated from the applied sinusoidal excitation and corresponding surface leakage current. Existing literature shows that surface leakage current of insulator is infested with odd harmonics though the applied voltage is sinusoidal in nature. The presence of harmonic contents in leakage current is due to non‐linear characteristics of the insulator surface owing to formation of dry bands. The nonlinear characteristic of the insulator surface depends on its contamination level which in turn affects the corresponding flashover voltage. Therefore, the harmonic configuration in leakage current can be correlated with the contamination level on insulator surface and corresponding flashover voltage. Considering the fact, in this contribution, a non‐linear equivalent circuit of insulator has been proposed based on harmonic components of the leakage current. For each harmonic component of the leakage current flowing through the insulator system, energy lost and energy stored in the system is calculated, which eventually enables to calculate dielectric dissipation factor. The proposed technique is applied for experimental investigation on 11 kV disc porcelain insulator artificially contaminated in the laboratory under controlled environmental conditions.
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril
Authors: Wälti Marielle Aulikki , Ravotti Francesco , Arai Hiromi , Glabe Charles G. , Wall Joseph S. , Böckmann Anja , Güntert Peter , Meier Beat H. , Riek Roland 
Published: July 2016

SignificanceAlzheimer’s disease is the most prevalent neurodegenerative disease still with no known cure. The disease is characterized by the development of extracellular plaques and intracellular neurofibrillary tangles. The senile plaques consist mainly of the peptide amyloid-β (Aβ) in aggregated form, called amyloid fibrils. It is believed that the Aβ amyloid fibrils play an important role in disease progression and cell-to-cell transmissibility, and small Aβ oligomers are often assumed to be the most neurotoxic species. Here, we determined the 3D structure of a disease-relevant Aβ(1–42) fibril polymorph combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM. The 3D structure is composed of two molecules per fibril layer, forming a double-horseshoe–like cross–β-sheet entity with maximally buried hydrophobic side chains.
Low Annual Fidelity and Early Upstream Migration of Anadromous Arctic Char in a Variable Environment
Authors: Gilbert Matthew J. H. , Donadt Caitlyn R. , Swanson Heidi K. , Tierney Keith B. 
Published: July 2016

AbstractThe life histories of anadromous Arctic Char Salvelinus alpinus are complex and vary greatly between populations and environments. Here, we detail key aspects of the physical environment and life history of a population of Arctic Char from Nulahugyuk Creek, Nunavut, Canada, to characterize migration traits in a highly variable environment. Over the course of this migration, creek discharge declined precipitously, forcing Arctic Char to migrate through shallow water with large diel temperature fluctuations (>10°C) and high temperature extremes (>21°C). The downstream migration of adults (>55 cm) began in mid‐June and continued into early July, while the downstream migration of smolts (<30 cm) began in late June and continued until late July. The upstream adult migration began in late June and ended in late July, far earlier than most upstream migrations in the region. There was no appreciable upstream migration of juveniles, and Arctic Char 30 to 55 cm in length were absent from the up‐ and downstream migrations. The average age at first migration was 4 years, and the youngest adult Arctic Char migrating upstream were 8 and 9 years old. The missing size‐ and age‐classes, and the fact that most upstream migrants were near reproductive maturity, indicate that Arctic Char in this system typically leave at a length of 19 cm and an age of 4 years and do not return for 4 to 5 years, when they are ready to reproduce. Anadromous Nulahugyuk Creek Arctic Char appear to employ strategies that limit their exposure to restrictive migratory conditions and facilitate their existence in an otherwise uninhabitable system. Understanding such population‐specific migratory strategies is critical to the management of Arctic Char fisheries, which are comprised of populations with highly diverse life histories, and to our understanding of how these life histories may contribute to the adaptability and persistence of the species as climate change progresses.Received November 24, 2015; accepted March 23, 2016 Published online July 28, 2016