bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidized nucleotide insertion by pol β confounds ligation during base excision repair
Authors: Çağlayan Melike , Horton Julie K. , Dai Da-Peng , Stefanick Donna F. , Wilson Samuel H. 
Published: January 2017

AbstractOxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro. These results suggest the possibility that BER mediated toxic strand breaks are produced in cells under oxidative stress conditions. We observe enhanced cytotoxicity in oxidizing-agent treated pol β expressing mouse fibroblasts, suggesting formation of DNA strand breaks under these treatment conditions. Increased cytotoxicity following MTH1 knockout or treatment with MTH1 inhibitor suggests the oxidation of precursor nucleotides.
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
Authors: Shirai Cara Lunn , White Brian S. , Tripathi Manorama , Tapia Roberto , Ley James N. , Ndonwi Matthew , Kim Sanghyun , Shao Jin , Carver Alexa , Saez Borja , Fulton Robert S. , Fronick Catrina , O’Laughlin Michelle , Lagisetti Chandraiah , Webb Thomas R. , Graubert Timothy A. , Walter Matthew J. 
Published: January 2017

AbstractSomatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity toin vitrosudemycin treatment relative to controls.In vivosudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouringU2AF1mutations with pre-mRNA splicing modulators like sudemycins.
Validity of visceral adiposity estimates from DXA against MRI in Kuwaiti men and women
Authors: Mohammad A , De Lucia Rolfe E , Sleigh A , Kivisild T , Behbehani K , Wareham N J , Brage S , Mohammad T 
Published: January 2017

Abstract
Objectives:
The prevalence of obesity and diabetes in the Middle East is among the highest in the world. Valid measures of abdominal adiposity are essential to understanding the metabolic consequences of obesity. Dual-energy X-ray absorptiometry (DXA) is increasingly being utilised to assess body composition in population studies, and has recently been used to estimate visceral adipose tissue (VAT). The aim of this study was to determine the accuracy of DXA-derived VAT in a Middle Eastern population using magnetic resonance imaging (MRI) as the criterion measure.

Method:
VAT was estimated from abdominal DXA measures in 237 adult men (n=130) and women (n=107), aged 18–65 years, participating in the Kuwait Wellbeing Study. These estimates were compared with MRI measures of the corresponding anatomical region. The agreement between methods was assessed using Bland–Altman as well as correlation analysis.

Results:
Median MRI VAT was 1148.5 cm3 (95% confidence interval: 594.2–1734.6) in men and 711.3 cm3 (95% confidence interval: 395.5–1042.8) in women. DXA estimates of VAT showed high correlations with corresponding MRI measures (r=0.94 (P<0.0001) in men; r=0.93 (P<0.0001) in women). DXA overestimated VAT with a mean bias (95% limits of agreement) of 79.7 cm3 (−767 to 963) in men and 46.8 cm3 (−482 to 866) in women. The imprecision of DXA increased with increasing VAT level in both men and women.

Conclusion:
DXA estimates of VAT are valid for use in Middle Eastern populations, although accuracy decreases with increasing level of visceral adiposity.
Impact of type 1 diabetes mellitus and celiac disease on nutrition and quality of life
Authors: Nunes-Silva J G , Nunes V S , Schwartz R P , MLSS Trecco S , Evazian D , Correa-Giannella M L , Nery M , Queiroz M S 
Published: January 2017

Abstract
Objective:
Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune diseases and have similar genetic patterns. T1DM treatment is based on diet, physical activity and insulin therapy, whereas CD depends on dietary changes with restriction of wheat, rye and barley. The aim of the study was to evaluate the quality of life (QoL) of individuals with the association of T1DM and CD, to characterize their nutritional status and to compare it with those with only one disease and healthier controls.

Subjects/Methods:
Sixty patients controlled by sex, age and body mass index (BMI) were stratified by previous diagnosis in: T1DM and CD (DMCD group); T1DM (DM group); CD (CD group); or healthy participants (HC). The SF-36 questionnaire was applied to assess psychological well being and results were compared with glycemic control and presence of complications related to diabetes, adhesion to gluten-free diet (GFD). Nutritional status and body mass composition were determined by BMI, waist circumference, bioimpedance, general laboratory tests and whole-body densitometry.

Results:
The time of diagnosis of T1DM was similar between DMCD and DM groups; however, the duration of CD was significantly higher in the CD group compared with DMCD. The SF-36 analysis revealed statistically significant differences between DM and HC groups in two domains: general health (P=0.042) and energy/vitality (P=0.012). QoL was also correlated with compliance to a GFD, and scores were similar in both groups: DMCD and CD. Forty percent of individuals in the CD group had visceral fat area above 100 cm2, as opposed to 20% in the other groups.

Conclusions:
Individuals of DMCD group had similar scores to DM, CD and HC on QoL, as well as on their nutritional status and bone metabolism. Thereby, we should conclude that the association of T1DM and CD did not deteriorate their health status.
Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer
Authors: Xiang J , Fu X , Ran W , Wang Z 
Published: January 2017

AbstractMetastasis is one of the typical features of malignancy that significantly increases cancer-related mortality. Recent studies have shown that epithelial–mesenchymal transition (EMT) is closely related to the invasion and migration of cancer cells. Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. In the previous study, we have reported that Grhl2 functioned as a tumor suppressor in proliferation and apoptosis of gastric cancer. Here we aim to explore the effects of Grhl2 on invasion and migration of gastric cancer and further clarify its possible underlying mechanisms. As a result, in both SGC7901 and MKN45 cells, Grhl2 overexpression significantly inhibited the ability of invasion and migration. In addition, preliminary experiments showed that Grhl2 reduces the protein expression of matrix metalloproteinase-2, -7 and -9 (MMP-2, MMP-7 and MMP-9). Most importantly, Grhl2 antagonizes transforming growth factor-β (TGFβ)-induced EMT, and inhibition of TGFβ signaling pathways can restore Grhl2 expression. Finally, the results of subcutaneous xenograft model indicated that Grhl2 suppresses the growth of gastric cancer and reverses EMT process in vivo. Meanwhile, the metastatic tumor model further confirmed the inhibition of Grhl2 on metastasis of gastric cancer. Taken together, our findings proved that Grhl2, functioned as a tumor suppressor, reduces the invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer.
Weak functional connectivity in the human fetal brain prior to preterm birth
Authors: Thomason Moriah E. , Scheinost Dustin , Manning Janessa H. , Grove Lauren E. , Hect Jasmine , Marshall Narcis , Hernandez-Andrade Edgar , Berman Susan , Pappas Athina , Yeo Lami , Hassan Sonia S. , Constable R. Todd , Ment Laura R. , Romero Roberto 
Published: January 2017

AbstractIt has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.
Association of Polymorphisms in three pri-miRNAs that Target Pepsinogen C with the Risk and Prognosis of Gastric Cancer
Authors: Wu Ye-feng , Xu Qian , He Cai-yun , Li Ying , Liu Jing-wei , Deng Na , Sun Li-ping , Yuan Yuan 
Published: January 2017

AbstractWe aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom’s MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup. MiR-365b rs121224 was associated with the risk of intestinal-type gastric cancer in the alcohol consumption subgroup. Intestinal-type gastric cancer patients at Borrmann stages III-IV who carry the miR-365b rs121224 GG genotype had better prognosis compared with those who carry the CG or CC genotypes. MiR-365b rs121224 was associated with Lauren typing and TNM staging, in which the distribution of GG genotype carriers in intestinal-type gastric cancer and the TNM stage I-II subgroup was higher than that of CG or CC genotypes, which contrasted with the distribution in diffuse-type gastric cancer or TNM III-IV groups. These findings suggested that the polymorphisms in these miRNAs might be biomarkers for gastric cancer risk and prognosis, especially for populations infected with Helicobacter pylori or who consume alcohol.
Serelaxin treatment reverses vascular dysfunction and left ventricular hypertrophy in a mouse model of Type 1 diabetes
Authors: Ng Hooi Hooi , Leo Chen Huei , Prakoso Darnel , Qin Chengxue , Ritchie Rebecca H. , Parry Laura J. 
Published: January 2017

AbstractSerelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups. After 12 weeks of diabetes, sensitivity to the endothelium-dependent agonist acetylcholine (ACh) was reduced in the mesenteric artery. This was accompanied by an enhanced vasoconstrictor prostanoid contribution and a decrease in endothelium-derived hyperpolarisation (EDH)-mediated relaxation. Serelaxin restored endothelial function by increasing nitric oxide (NO)-mediated relaxation but not EDH. It also normalised the contribution of vasoconstrictor prostanoids to endothelial dysfunction and suppressed diabetes-induced hyper-responsiveness of the mesenteric artery to angiotensin II. Similarly, diabetes reduced ACh-evoked NO-mediated relaxation in the aorta which was reversed by serelaxin. In the left ventricle, diabetes promoted apoptosis, hypertrophy and fibrosis; serelaxin treatment reversed this ventricular apoptosis and hypertrophy, but had no effect on fibrosis. In summary, serelaxin reversed diabetes-induced endothelial dysfunction by enhancing NO-mediated relaxation in the mouse vasculature and attenuating left ventricular hypertrophy and apoptosis.
Real-time oxide evolution of copper protected by graphene and boron nitride barriers
Authors: Galbiati M. , Stoot A. C. , Mackenzie D. M. A. , Bøggild P. , Camilli L. 
Published: January 2017

AbstractApplying protective or barrier layers to isolate a target item from the environment is a common approach to prevent or delay its degradation. The impermeability of two-dimensional materials such as graphene and hexagonal boron nitride (hBN) has generated a great deal of interest in corrosion and material science. Owing to their different electronic properties (graphene is a semimetal, whereas hBN is a wide-bandgap insulator), their protection behaviour is distinctly different. Here we investigate the performance of graphene and hBN as barrier coatings applied on copper substrates through a real-time study in two different oxidative conditions. Our findings show that the evolution of the copper oxidation is remarkably different for the two coating materials.
Sec16A is critical for both conventional and unconventional secretion of CFTR
Authors: Piao He , Kim Jiyoon , Noh Shin Hye , Kweon Hee-Seok , Kim Joo Young , Lee Min Goo 
Published: January 2017

AbstractCFTR is a transmembrane protein that reaches the cell surface via the conventional Golgi mediated secretion pathway. Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type CFTR and the disease-causing ΔF508-CFTR, which has folding and trafficking defects. Here, we show that Sec16A, the key regulator of conventional ER-to-Golgi transport, plays a critical role in the ER exit of protein cargos during unconventional secretion. In an initial gene silencing screen, Sec16A knockdown abolished the unconventional secretion of wild-type and ΔF508-CFTR induced by ER-to-Golgi blockade, whereas the knockdown of other COPII-related components did not. Notably, during unconventional secretion, Sec16A was redistributed to cell periphery and associated with GRASP55 in mammalian cells. Molecular and morphological analyses revealed that IRE1α-mediated signaling is an upstream regulator of Sec16A during ER-to-Golgi blockade or ER stress associated unconventional secretion. These findings highlight a novel function of Sec16A as an essential mediator of ER stress-associated unconventional secretion.
Perceptual similarity and the neural correlates of geometrical illusions in human brain structure
Authors: Axelrod Vadim , Schwarzkopf D. Samuel , Gilaie-Dotan Sharon , Rees Geraint 
Published: January 2017

AbstractGeometrical visual illusions are an intriguing phenomenon, in which subjective perception consistently misjudges the objective, physical properties of the visual stimulus. Prominent theoretical proposals have been advanced attempting to find common mechanisms across illusions. But empirically testing the similarity between illusions has been notoriously difficult because illusions have very different visual appearances. Here we overcome this difficulty by capitalizing on the variability of the illusory magnitude across participants. Fifty-nine healthy volunteers participated in the study that included measurement of individual illusion magnitude and structural MRI scanning. We tested the Muller-Lyer, Ebbinghaus, Ponzo, and vertical-horizontal geometrical illusions as well as a non-geometrical, contrast illusion. We found some degree of similarity in behavioral judgments of all tested geometrical illusions, but not between geometrical illusions and non-geometrical, contrast illusion. The highest similarity was found between Ebbinghaus and Muller-Lyer geometrical illusions. Furthermore, the magnitude of all geometrical illusions, and particularly the Ebbinghaus and Muller-Lyer illusions, correlated with local gray matter density in the parahippocampal cortex, but not in other brain areas. Our findings suggest that visuospatial integration and scene construction processes might partly mediate individual differences in geometric illusory perception. Overall, these findings contribute to a better understanding of the mechanisms behind geometrical illusions.
Effect of hierarchically aligned fibrin hydrogel in regeneration of spinal cord injury demonstrated by tractography: A pilot study
Authors: Zhang Zhenxia , Yao Shenglian , Xie Sheng , Wang Xiumei , Chang Feiyan , Luo Jie , Wang Jingming , Fu Jun 
Published: January 2017

AbstractSome studies have reported that scaffold or cell-based transplantation may improve functional recovery following SCI, but no imaging information regarding regeneration has been provided to date. This study used tractography to show the regenerating process induced by a new biomaterial-aligned fibrin hydrogel (AFG). A total of eight canines subjected to SCI procedures were assigned to the control or the AFG group. AFG was implanted into the SCI lesion immediately after injury in 5 canines. A follow-up was performed at 12 weeks to evaluate the therapeutic effect including the hindlimb functional recovery, anisotropy and continuity of fibers on tractography. Using tractography, we found new fibers running across the SCI in three canines of the AFG group. Further histological examination confirmed limited glial scarring and regenerated nerve fibers in the lesions. Moreover, Repeated Measures Analysis revealed a significantly different change in fractional anisotropy (FA) between the two groups during the follow-up interval. An increase in FA during the post injury time interval was detected in the AFG group, indicating a beneficial effect of AFG in the rehabilitation of injured axons. Using tractography, AFG was suggested to be helpful in the restoration of fibers in SCI lesions, thus leading to promoted functional recovery.
Polarization-Controlled Broad Color Palette Based on an Ultrathin One-Dimensional Resonant Grating Structure
Authors: Koirala Ishwor , Shrestha Vivek Raj , Park Chul-Soon , Lee Sang-Shin , Choi Duk-Yong 
Published: January 2017

AbstractHighly efficient polarization-tuned structural color filters, which are based on a one- dimensional resonant aluminum grating that is integrated with a silicon nitride waveguide, are proposed and demonstrated to feature a broad color palette. For such a metallic grating structure, transmissive color filtering is only feasible for the incident transverse-magnetic (TM) polarization due to its high reflection regarding the transverse-electric (TE) case; however, polarization-tuned customized colors can be efficiently achieved by optimizing the structural parameters like the duty ratio of the metallic grating. For the fabricated color filters, the transmission peaks, which are imputed to the resonance between the incident light and the guided modes that are supported by the dielectric waveguide, provided efficiencies as high as 90% and 70% for the TM and TE polarizations, respectively, as intended. Through the tailoring of the polarization, a group of filters with different grating periods were successfully exploited to produce a broad color palette spanning the entire visible band. Lastly, a nanoscale alphabetic pattern featuring a flexible combination of colorations was practically constructed via an arrangement of horizontal and vertical gratings.
A new method for assessing the risk of infectious disease outbreak
Authors: Liao Yilan , Xu Bing , Wang Jinfeng , Liu Xiaochi 
Published: January 2017

AbstractOver the past few years, emergent threats posed by infectious diseases and bioterrorism have become public health concerns that have increased the need for prompt disease outbreak warnings. In most of the existing disease surveillance systems, disease outbreak risk is assessed by the detection of disease outbreaks. However, this is a retrospective approach that impacts the timeliness of the warning. Some disease surveillance systems can predict the probabilities of infectious disease outbreaks in advance by determining the relationship between a disease outbreak and the risk factors. However, this process depends on the availability of risk factor data. In this article, we propose a Bayesian belief network (BBN) method to assess disease outbreak risks at different spatial scales based on cases or virus detection rates. Our experimental results show that this method is more accurate than traditional methods and can make uncertainty estimates, even when some data are unavailable.
Unusual respiratory capacity and nitrogen metabolism in a Parcubacterium (OD1) of the Candidate Phyla Radiation
Authors: Castelle Cindy J. , Brown Christopher T. , Thomas Brian C. , Williams Kenneth H. , Banfield Jillian F. 
Published: January 2017

AbstractThe Candidate Phyla Radiation (CPR) is a large group of bacteria, the scale of which approaches that of all other bacteria. CPR organisms are inferred to depend on other community members for many basic cellular building blocks and all appear to be obligate anaerobes. To date, there has been no evidence for any significant respiratory capacity in an organism from this radiation. Here we report a curated draft genome for ‘Candidatus Parcunitrobacter nitroensis’ a member of the Parcubacteria (OD1) superphylum of the CPR. The genome encodes versatile energy pathways, including fermentative and respiratory capacities, nitrogen and fatty acid metabolism, as well as the first complete electron transport chain described for a member of the CPR. The sequences of all of these enzymes are highly divergent from sequences found in other organisms, suggesting that these capacities were not recently acquired from non-CPR organisms. Although the wide respiration-based repertoire points to a different lifestyle compared to other CPR bacteria, we predict similar obligate dependence on other organisms or the microbial community. The results substantially expand the known metabolic potential of CPR bacteria, although sequence comparisons indicate that these capacities are very rare in members of this radiation.
Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer
Authors: Zhu Yingdong , Wang Fang , Zhao Yantao , Wang Pei , Sang Shengmin 
Published: January 2017

AbstractA growing body of research suggests daily low-dose aspirin (ASA) reduces heart diseases and colorectal cancers. However, the major limitation to the use of aspirin is its side effect to cause ulceration and bleeding in the gastrointestinal tract. Preclinical studies have shown that ginger constituents ameliorate ASA-induced gastric ulceration. We here report the design and synthesis of a novel prodrug of aspirin, [6]-gingerol aspirinate (GAS). Our data show that GAS exerts enhanced anti-cancer properties in vitro and superior gastroprotective effects in mice. GAS was also able to survive stomach acid and decomposed in intestinal linings or after absorption to simultaneously release ASA and [6]-gingerol. We further present that GAS inactivates both COX-1 and COX-2 equally. Our results demonstrate the enhanced anticancer properties along with gastroprotective effects of GAS, suggesting that GAS can be a therapeutic equivalent for ASA in inflammatory and proliferative diseases without the deleterious effects on stomach mucosa.