bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair
Authors: Liao Jinfeng , Tian Taoran , Shi Sirong , Xie Xueping , Ma Quanquan , Li Guo , Lin Yunfeng 
Published: July 2017

AbstractCartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.
The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years
Authors: Liu Ting-ting , Liu Dong-mei , Xuan Yan , Zhao Lin , Sun Li-hao , Zhao Dian-dian , Wang Xiao-feng , He Yang , Guo Xing-Zhi , Du Rui , Wang Ji-qiu , Liu Jian-min , Zhao Hong-yan , Tao Bei 
Published: July 2017

AbstractBone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%–30.7%)] compared with the lower [31.0% (95% CI, 17.2%–46.1%)] and upper [46.5% (95% CI, 31.2%–62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P=0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73–28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis
Authors: Wiktor Maciej , Weichert Dietmar , Howe Nicole , Huang Chia-Ying , Olieric Vincent , Boland Coilín , Bailey Jonathan , Vogeley Lutz , Stansfeld Phillip J. , Buddelmeijer Nienke , Wang Meitian , Caffrey Martin 
Published: July 2017

AbstractLipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein’s invariant diacylated N-terminal cysteine. Structures of Lnt fromPseudomonas aeruginosaandEscherichia colihave been solved; they are remarkably similar. Both consist of a membrane domain on which sits a globular periplasmic domain. The active site resides above the membrane interface where the domains meet facing into the periplasm. The structures are consistent with the proposed ping-pong reaction mechanism and suggest plausible routes by which substrates and products enter and leave the active site. While Lnt may present challenges for antibiotic development, the structures described should facilitate design of therapeutics with reduced off-target effects.
Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals
Authors: Posth Cosimo , Wißing Christoph , Kitagawa Keiko , Pagani Luca , van Holstein Laura , Racimo Fernando , Wehrberger Kurt , Conard Nicholas J. , Kind Claus Joachim , Bocherens Hervé , Krause Johannes 
Published: July 2017

AbstractAncient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago. Here we report the complete mtDNA of an archaic femur from the Hohlenstein–Stadel (HST) cave in southwestern Germany. HST carries the deepest divergent mtDNA lineage that splits from other Neanderthals ∼270,000 years ago, providing a lower boundary for the time of the putative mtDNA introgression event. We demonstrate that a complete Neanderthal mtDNA replacement is feasible over this time interval even with minimal hominin introgression. The highly divergent HST branch is indicative of greater mtDNA diversity during the Middle Pleistocene than in later periods.
CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process
Authors: Wang Jimeng , Gao Yi , Cheng Pengzhen , Li Donglin , Jiang Huijie , Ji Chuanlei , Zhang Shuaishuai , Shen Chao , Li Junqin , Song Yue , Cao Tianqing , Wang Chunmei , Yang Liu , Pei Guoxian 
Published: July 2017

AbstractCD31hiEmcnhi vessels were a subtype of vessels in the murine skeletal system, with high levels of platelet and endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endomucin (Emcn). They were reported coupling angiogenesis and osteogenesis during bone development. We investigated the distribution of these vessels in rat tibiae and their temporal and spatial distribution during the bone defect repair process to improve our understanding of the importance of these vessels. We confirmed that CD31hiEmcnhi vessels were specially distributed around the trabecular bones near metaphysis and endosteum in rat tibiae. At 3 days post bone injury, CD31hiEmcnhi vessels proliferated and were extensively distributed across the entire repair area. At 7 and 14 days post-injury, these vessels decreased but were specially distributed around the growing trabecular bones near the frontier growth area, suggesting that these vessels support new bone formation. The distribution of CD31hiEmcnhi vessels and the transcriptions of Hif-1α and VEGFA, as well as BMP2 and Osterix decreased at 7 and 14 days post-injury under osteoporotic conditions, in combination with insufficient osteogenesis. Our research is of great significance to help understand the important role of CD31hiEmcnhi vessels in supporting new trabecular bones formation during bone defect repair process.
A Simple Analytical Model for Magnetization and Coercivity of Hard/Soft Nanocomposite Magnets
Authors: Park Jihoon , Hong Yang-Ki , Lee Woncheol , Kim Seong-Gon , Rong Chuangbing , Poudyal Narayan , Liu J. Ping , Choi Chul-Jin 
Published: July 2017

AbstractWe present a simple analytical model to estimate the magnetization (σs) and intrinsic coercivity (Hci) of a hard/soft nanocomposite magnet using the mass fraction. Previously proposed models are based on the volume fraction of the hard phase of the composite. However, it is difficult to measure the volume of the hard or soft phase material of a composite. We synthesized Sm2Co7/Fe-Co, MnAl/Fe-Co, MnBi/Fe-Co, and BaFe12O19/Fe-Co composites for characterization of their σs and Hci. The experimental results are in good agreement with the present model. Therefore, this analytical model can be extended to predict the maximum energy product (BH)max of hard/soft composite.
Climate Classification is an Important Factor in Assessing Quality-of-Care Across Hospitals
Authors: Boland Mary Regina , Parhi Pradipta , Gentine Pierre , Tatonetti Nicholas P. 
Published: July 2017

AbstractClimate is a known modulator of disease, but its impact on hospital performance metrics remains unstudied. We assess the relationship between Köppen-Geiger climate classification and hospital performance metrics, specifically 30-day mortality, as reported in Hospital Compare, and collected for the period July 2013 through June 2014 (7/1/2013–06/30/2014). A hospital-level multivariate linear regression analysis was performed while controlling for known socioeconomic factors to explore the relationship between all-cause mortality and climate. Hospital performance scores were obtained from 4,524 hospitals belonging to 15 distinct Köppen-Geiger climates and 2,373 unique counties. Model results revealed that hospital performance metrics for mortality showed significant climate dependence (p < 0.001) after adjusting for socioeconomic factors. Climate is a significant factor in evaluating hospital 30-day mortality rates. These results demonstrate that climate classification is an important factor when comparing hospital performance across the United States.
Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury
Authors: Hill Lisa J. , Di Pietro Valentina , Hazeldine Jon , Davies David , Toman Emma , Logan Ann , Belli Antonio 
Published: July 2017

AbstractTraumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4–12 hr and 48–72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.
Epidermal growth factor receptor intron-1 CA repeat polymorphism on protein expression and clinical outcome in Taiwanese oral squamous cell carcinoma
Authors: Huang Shiang-Fu , Chien Huei-Tzu , Chuang Wen-Yu , Lai Chih-Hsiung , Cheng Sou-De , Liao Chun-Ta , Wang Hung-Ming 
Published: July 2017

AbstractThis study was designed to explore the relationship between epidermal growth factor receptor (EGFR) CA repeats polymorphism and protein expression in oral cavity squamous cell carcinoma (OSCC). A total of 194 OSCCs were examined for EGFR protein overexpression, gene copy number and the length of their CA repeats. The length of the EGFR CA repeats was found not to be associated with EGFR gene copy number or with protein overexpression. To exclude the effect of EGFR gene copy number on protein overexpression, only those OSCC tumors with disomy of the EGFR gene were included in further analysis. In this subgroup, EGFR protein overexpression was significantly associated with poor differentiation of the tumor cells and lymph node metastasis, especially extra-capsular spread. However, EGFR CA repeats were not related to any clinicopathological factor. Interestingly, patients genetically found to have the EGFR CA repeats SS genotype and having tumors with EGFR protein overexpression were found to have a worst prognosis in terms of disease-free survival (DFS) (HR = 2.68; 95% CI, 1.03–6.98) after multivariate adjustment. The present study demonstrates that concurrent overexpression of EGFR protein in the presence genetically of the SS form CA repeats acts as a predictor for poor DFS.
Presence of diabetes autoantigens in extracellular vesicles derived from human islets
Authors: Hasilo Craig P. , Negi Sarita , Allaeys Isabelle , Cloutier Nathalie , Rutman Alissa K. , Gasparrini Marco , Bonneil Éric , Thibault Pierre , Boilard Éric , Paraskevas Steven 
Published: July 2017

AbstractBeta-cell (β-cell) injury is the hallmark of autoimmune diabetes. However, the mechanisms by which autoreactive responses are generated in susceptible individuals are not well understood. Extracellular vesicles (EV) are produced by mammalian cells under normal and stressed physiological states. They are an important part of cellular communication, and may serve a role in antigen processing and presentation. We hypothesized that isolated human islets in culture produce EV that contain diabetes autoantigens (DAA) from these otherwise normal, non-diabetic donors. Here we report the caspase-independent production of EV by human islets in culture, and the characterization of DAA glutamic acid decarboxylase 65 (GAD65) and zinc transporter 8 (ZnT8), as well as the β-cell resident glucose transporter 2 (Glut2), present within the EV.
Laquinimod treatment in the R6/2 mouse model
Authors: Ellrichmann Gisa , Blusch Alina , Fatoba Oluwaseun , Brunner Janine , Reick Christiane , Hayardeny Liat , Hayden Michael , Sehr Dominik , Winklhofer Konstanze F. , Saft Carsten , Gold Ralf 
Published: July 2017

AbstractThe transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-cell-line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.
The Pawnee earthquake as a result of the interplay among injection, faults and foreshocks
Authors: Chen Xiaowei , Nakata Nori , Pennington Colin , Haffener Jackson , Chang Jefferson C. , He Xiaohui , Zhan Zhongwen , Ni Sidao , Walter Jacob I. 
Published: July 2017

AbstractThe Pawnee M5.8 earthquake is the largest event in Oklahoma instrument recorded history. It occurred near the edge of active seismic zones, similar to other M5+ earthquakes since 2011. It ruptured a previously unmapped fault and triggered aftershocks along a complex conjugate fault system. With a high-resolution earthquake catalog, we observe propagating foreshocks leading to the mainshock within 0.5 km distance, suggesting existence of precursory aseismic slip. At approximately 100 days before the mainshock, two M ≥ 3.5 earthquakes occurred along a mapped fault that is conjugate to the mainshock fault. At about 40 days before, two earthquakes clusters started, with one M3 earthquake occurred two days before the mainshock. The three M ≥ 3 foreshocks all produced positive Coulomb stress at the mainshock hypocenter. These foreshock activities within the conjugate fault system are near-instantaneously responding to variations in injection rates at 95% confidence. The short time delay between injection and seismicity differs from both the hypothetical expected time scale of diffusion process and the long time delay observed in this region prior to 2016, suggesting a possible role of elastic stress transfer and critical stress state of the fault. Our results suggest that the Pawnee earthquake is a result of interplay among injection, tectonic faults, and foreshocks.
Climate change impacts on the threatened terrestrial vertebrates of the Pacific Islands
Authors: Kumar Lalit , Tehrany Mahyat Shafapour 
Published: July 2017

AbstractThe aim of this study was to undertake a broad-scale understanding of the distribution of vulnerable, endangered and critically endangered terrestrial vertebrate species in the Pacific and the assessment of impacts of climate change and sea level rise. 150 critically endangered, endangered and vulnerable terrestrial vertebrates found in 23 countries of the Pacific were linked to island susceptibility to climate change. Out of the 1779 islands making up the 23 countries, 674 of them hosted at least one species from the above categories. 84 of the 150 species are endemic to this study area and many of these occur on islands with high susceptibility to climate change, with many of them occurring on one island only. The species data, together with islands, was overlain with Mean Significant Wave Height (Hs) projections for 2081–2100 under RCP4.5 and 8.5, and further analysed for threat of extinction. A large number of critically endangered and endangered species fall in regions that have the highest Hs projections.
Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2
Authors: Zhang Lei , Song Jun , Bai Tao , Qian Wei , Hou Xiao-Hua 
Published: July 2017

AbstractPsychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer’s lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo. Decreased transepithelial resistance (TER) and increased paracellular and transcellular macromolecular permeability in colon, ileal VE and FAE had been observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium obviously alleviated the barrier disruption induced by WAS in vivo and CRF in vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2 antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability. Altogether, it concluded that the FAE was more susceptible to stress, and the mast cells and PAR2 signaling played crucial roles in this process.
Reachability and the sense of embodiment in amputees using prostheses
Authors: Gouzien Adrienne , de Vignemont Fréderique , Touillet Amélie , Martinet Noël , De Graaf Jozina , Jarrassé Nathanaël , Roby-Brami Agnès 
Published: July 2017

AbstractAmputated patients are hardly satisfied with upper limb prostheses, and tend to favour the use of their contralateral arm to partially compensate their disability. This may seem surprising in light of recent evidences that external objects (rubber hand or tool) can easily be embodied, namely incorporated in the body representation. We investigated both implicit body representations (by evaluating the peripersonal space using a reachability judgement task) and the quality of bodily integration of the patient’s prosthesis (assessed via questionnaires). As expected, the patients estimated that they could reach further while wearing their prosthesis, showing an embodiment of their prosthesis in their judgement. Yet, the real reaching space was found to be smaller with their prosthesis than with their healthy limb, showing a large error between reachability judgement and actual capacity. An overestimation was also found on the healthy side (comparatively to healthy subjects) suggesting a bilateral modification of body representation in amputated patients. Finally, a correlation was found between the quality of integration of the prosthesis and the way the body representation changed. This study therefore illustrates the multifaceted nature of the phenomenon of prosthesis integration, which involves its incorporation as a tool, but also various specific subjective aspects.
C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
Authors: Blain Jennifer , Bédard Jessily , Thompson Maureen , Boisvert François-Michel , Boucher Marie-Josée 
Published: July 2017

AbstractSince the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1ICD), many laboratories have exploited this model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be underscored that Cre-recombination leads to the expression of a C-terminally truncated form of N1ICD (N1ICDdC) in the RosaN1-ICD mutant mice. Given that no studies were undertaken to delineate whether deletion of this region leaves intact N1ICD function, stable cell lines with single targeted integration of inducible N1ICD and N1ICDdC were generated. We found that C-terminal deletion of N1ICD stabilized the protein but did not promote the activity of Notch responsive promoters. Furthermore, despite higher expression levels, N1ICDdC failed to phenocopy N1ICD in the promotion of anchorage-independent growth. Our results thus suggest that the C-terminal region of N1ICD plays a role in shaping the Notch response. Therefore, it should be taken into consideration that N1ICD is truncated when interpreting phenotypes of RosaN1-ICD mutant mice.