bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis
Authors: Deshmukh Jayesh , Pofahl Ruth , Haase Ingo 
Published: March 2017

AbstractNon-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytesin vitroas well asin vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53,γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.
MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy
Authors: Zhou Zhanmei , Wan Jiao , Hou Xiaoyan , Geng Jian , Li Xiao , Bai Xiaoyan 
Published: March 2017

AbstractPodocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin pathways have been involved in the pathogenesis of DN. Herein, we asked whether miR-27a mediates podocyte injury through PPARγ/β-catenin signaling in DN. The functional relevance of miR-27a, PPARγ and β-catenin were investigated in cultured podocytes and glomeruli of diabetic rats and patients using in vitro and in vivo approaches. Podocyte injury was assessed by migration, invasion and apoptosis assay. Biological parameters were analyzed using enzyme-linked immunosorbent assay. We found that high glucose stimulated miR-27a expression, which, by negatively targeting PPARγ, activated β-catenin signaling as evidenced by upregulation of β-catenin target genes, snail1 and α-smooth muscle actin (α-SMA) and downregulation of podocyte-specific markers podocin and synaptopodin. These changes caused podocyte injury as demonstrated by increased podocyte mesenchymal transition, disrupted podocyte architectural integrity and increased podocyte apoptosis. Furthermore, we provide evidence that miR-27a contributed to unfavorable renal function and increased podocyte injury in diabetic rats. Notably, miR-27a exhibited clinical and biological relevance as it was linked to elevated serum creatinine, proteinuria and reduced creatinine clearance rate. In addition, miR-27a upregulation and activation of PPARγ/β-catenin signaling were verified in renal biopsy samples from DN patients. We propose a novel role of the miR-27a/PPARγ/β-catenin axis in fostering the progression toward more deteriorated podocyte injury in DN. Targeting miR-27a could be a potential therapeutic approach for DN.
Optimal adaptive control for quantum metrology with time-dependent Hamiltonians
Authors: Pang Shengshi , Jordan Andrew N. 
Published: March 2017

AbstractQuantum metrology has been studied for a wide range of systems with time-independent Hamiltonians. For systems with time-dependent Hamiltonians, however, due to the complexity of dynamics, little has been known about quantum metrology. Here we investigate quantum metrology with time-dependent Hamiltonians to bridge this gap. We obtain the optimal quantum Fisher information for parameters in time-dependent Hamiltonians, and show proper Hamiltonian control is generally necessary to optimize the Fisher information. We derive the optimal Hamiltonian control, which is generally adaptive, and the measurement scheme to attain the optimal Fisher information. In a minimal example of a qubit in a rotating magnetic field, we find a surprising result that the fundamental limit of T2 time scaling of quantum Fisher information can be broken with time-dependent Hamiltonians, which reaches T4 in estimating the rotation frequency of the field. We conclude by considering level crossings in the derivatives of the Hamiltonians, and point out additional control is necessary for that case.
CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis
Authors: Barthels Christian , Ogrinc Ana , Steyer Verena , Meier Stefanie , Simon Ferdinand , Wimmer Maria , Blutke Andreas , Straub Tobias , Zimber-Strobl Ursula , Lutgens Esther , Marconi Peggy , Ohnmacht Caspar , Garzetti Debora , Stecher Bärbel , Brocker Thomas 
Published: March 2017

AbstractImmune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+(RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+DCs in LP and a low frequency of RORγt+Helios−iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity.
Observation of stable Néel skyrmions in cobalt/palladium multilayers with Lorentz transmission electron microscopy
Authors: Pollard Shawn D. , Garlow Joseph A. , Yu Jiawei , Wang Zhen , Zhu Yimei , Yang Hyunsoo 
Published: March 2017

AbstractNéel skyrmions are of high interest due to their potential applications in a variety of spintronic devices, currently accessible in ultrathin heavy metal/ferromagnetic bilayers and multilayers with a strong Dzyaloshinskii–Moriya interaction. Here we report on the direct imaging of chiral spin structures including skyrmions in an exchange-coupled cobalt/palladium multilayer at room temperature with Lorentz transmission electron microscopy, a high-resolution technique previously suggested to exhibit no Néel skyrmion contrast. Phase retrieval methods allow us to map the internal spin structure of the skyrmion core, identifying a 25 nm central region of uniform magnetization followed by a larger region characterized by rotation from in- to out-of-plane. The formation and resolution of the internal spin structure of room temperature skyrmions without a stabilizing out-of-plane field in thick magnetic multilayers opens up a new set of tools and materials to study the physics and device applications associated with chiral ordering and skyrmions.
Triamidoamine thorium-arsenic complexes with parent arsenide, arsinidiide and arsenido structural motifs
Authors: Wildman Elizabeth P. , Balázs Gábor , Wooles Ashley J. , Scheer Manfred , Liddle Stephen T. 
Published: March 2017

AbstractDespite a major expansion of uranium–ligand multiple bond chemistry in recent years, analogous complexes involving other actinides (An) remain scarce. For thorium, under ambient conditions only a few multiple bonds to carbon, nitrogen, phosphorus and chalcogenides are reported, and none to arsenic are known; indeed only two complexes with thorium–arsenic single bonds have been structurally authenticated, reflecting the challenges of stabilizing polar linkages at the large thorium ion. Here, we report thorium parent–arsenide (ThAsH2), –arsinidiides (ThAs(H)K and ThAs(H)Th) and arsenido (ThAsTh) linkages stabilized by a bulky triamidoamine ligand. The ThAs(H)K and ThAsTh linkages exhibit polarized-covalent thorium–arsenic multiple bonding interactions, hitherto restricted to cryogenic matrix isolation experiments, and the AnAs(H)An and AnAsAn linkages reported here have no precedent in f-block chemistry. 7s, 6d and 5f orbital contributions to the Th–As bonds are suggested by quantum chemical calculations, and their compositions unexpectedly appear to be tensioned differently compared to phosphorus congeners.
Clinical characteristics of anti-SAE antibodies in Chinese patients with dermatomyositis in comparison with different patient cohorts
Authors: Ge Yongpeng , Lu Xin , Shu Xiaoming , Peng Qinglin , Wang Guochun 
Published: March 2017

AbstractThis study aimed to analyze the clinical features of anti-SAE antibodies in Chinese myositis patients in comparison with different cohorts. The anti-SAE antibodies were tested in myositis patients and in control subjects. Long-term follow-up was conducted on the antibody-positive patients. Anti-SAE antibodies were exclusively present in 12 out of 394 (3.0%) adult dermatomyositis (DM) patients. Of the anti-SAE-positive DM patients, 75% had distinctive diffuse dark-red or pigment-like skin rashes, and 67% of these patients experienced mild muscle weakness. Muscular biopsies showed mild pathological manifestations. Compared with the antibody-negative group, the average age of dermatomyositis onset in the antibody-positive group was higher, and dysphagia occurred more frequently noted (p = 0.012). Only 9 patients received follow-up, 7 experienced improvement after treatment. The anti-SAE antibody levels correlated with improved disease condition. The anti-SAE antibody was found exclusively in adult DM patients, occurring infrequently in Chinese patients. In addition to a diffuse dark-red or pigment-like skin rash and mild muscular weakness, common symptoms included propensity for developing dysphagia. Serum levels of the anti-SAE antibody correlated with myositis disease activity, and anti-SAE-positive patients were responsive to treatment.
Strong antibiotic production is correlated with highly active oxidative metabolism in Streptomyces coelicolor M145
Authors: Esnault Catherine , Dulermo Thierry , Smirnov Aleksey , Askora Ahmed , David Michelle , Deniset-Besseau Ariane , Holland Ian-Barry , Virolle Marie-Joelle 
Published: March 2017

AbstractThe Streptomyces genus is well known for its ability to produce bio-active secondary metabolites of great medical interest. However, the metabolic features accompanying these bio-productions remain to be defined. In this study, the comparison of related model strains producing differing levels of actinorhoddin (ACT), showed that S. lividans, a weak producer, had high TriAcylGlycerol (TAG) content indicative of a glycolytic metabolism. In contrast, the strong producer, S. coelicolor, was characterized by low TAG content, active consumption of its polyphosphate (PolyP) stores and extremely high ATP/ADP ratios. This indicated highly active oxidative metabolism that was correlated with induction of ACT biosynthesis. Interestingly, in conditions of phosphate limitation, the ppk mutant had TAG content and ACT production levels intermediary between those of S. lividans and S. coelicolor. This strain was characterized by high ADP levels indicating that Ppk was acting as an Adenosine Di Phosphate Kinase. Its absence resulted in energetic stress that is proposed to trigger an activation of oxidative metabolism to restore its energetic balance. This process, which is correlated with ACT biosynthesis, requires acetylCoA to fuel the Krebs cycle and phosphate for ATP generation by the ATP synthase coupled to the respiratory chain, resulting in low TAG and polyP content of the ACT producing strains.
Hybrid Magnetic-DNA Directed Immobilisation Approach for Efficient Protein Capture and Detection on Microfluidic Platforms
Authors: Esmaeili Elaheh , Ghiass Mohammad Adel , Vossoughi Manouchehr , Soleimani Masoud 
Published: March 2017

AbstractIn this study, a hybrid magnetic-DNA directed immobilisation approach is presented to enhance protein capture and detection on a microfluidic platform. DNA-modified magnetic nanoparticles are added in a solution to capture fluorescently labelled immunocomplexes to be detected optically. A magnetic set-up composed of cubic permanent magnets and a microchannel was designed and implemented based on finite element analysis results to efficiently concentrate the nanoparticles only over a defined area of the microchannel as the sensing zone. This in turn, led to the fluorescence emission localisation and the searching area reduction. Also, compared to processes in which the immunocomplex is formed directly on the surface, the proposed approach provides a lower steric hindrance, higher mass transfer, lower equilibrium time, and more surface concentration of the captured targets leading to a faster and more sensitive detection. As a proof-of-concept, the set-up is capable of detecting prostate-specific membrane antigen with concentrations down to 0.7 nM. Our findings suggest that the approach holds a great promise for applications in clinical assays and disease diagnosis.
Novel mutations in CRYGC are associated with congenital cataracts in Chinese families
Authors: Zhong Zilin , Wu Zehua , Han Liyun , Chen Jianjun 
Published: March 2017

AbstractCongenital cataract (CC), responsible for about one-third of blindness in infants, is a major cause of vision loss in children worldwide. 10–25% of CC cases are attributed to genetic causes and CC is a clinically and genetically highly heterogeneous lens disorder in children. Autosomal dominant (AD) inheritance is the most commonly pattern. 195 unrelated non-syndromic ADCC families in this study are recruited from 15 provinces of China. Sanger sequencing approach followed by intra-familial co-segregation, in Silico analyses and interpretation of the variations according to the published guidelines of American College of Medical Genetics (ACMG), were employed to determine the genetic defects. Two mutations (p.Tyr139X and p.Ser166Phe) identified in two unrelated families were associated with their congenital nuclear cataracts and microcornea respectively, which are also reported previously. Six novel CRYGC mutations (p.Asp65ThrfsX38, p.Arg142GlyfsX5, p.Arg142AlafsX22, p.Tyr144X, p.Arg169X, and p.Tyr46Asp) were identified in other six families with congenital nuclear cataracts, respectively. Mutations in the CRYGC were responsible for 4.1% Chinese ADCC families in our cohort. Our results expand the spectrum of CRYGC mutations as well as their associated phenotypes.
Human pressures and ecological status of European rivers
Authors: Grizzetti B. , Pistocchi A. , Liquete C. , Udias A. , Bouraoui F. , van de Bund W. 
Published: March 2017

AbstractHumans have increased the discharge of pollution, altered water flow regime and modified the morphology of rivers. All these actions have resulted in multiple pressures on freshwater ecosystems, undermining their biodiversity and ecological functioning. The European Union has adopted an ambitious water policy to reduce pressures and achieve a good ecological status for all water bodies. However, assessing multiple pressures on aquatic ecosystems and understanding their combined impact on the ecological status is challenging, especially at the large scale, though crucial to the planning of effective policies. Here, for the first time, we quantify multiple human pressures and their relationship with the ecological status for all European rivers. We considered ecological data collected across Europe and pressures assessed by pan-European models, including pollution, hydrological and hydromorphological alterations. We estimated that in one third of EU’s territory rivers are in good ecological status. We found that better ecological status is associated with the presence of natural areas in floodplains, while urbanisation and nutrient pollution are important predictors of ecological degradation. We explored scenarios of improvement of rivers ecological status for Europe. Our results strengthen the need to halt urban land take, curb nitrogen pollution and maintain and restore nature along rivers.
Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence
Authors: Krøigård Anne Bruun , Larsen Martin Jakob , Brasch-Andersen Charlotte , Lænkholm Anne-Vibeke , Knoop Ann S. , Jensen Jeanette Dupont , Bak Martin , Mollenhauer Jan , Thomassen Mads , Kruse Torben A. 
Published: March 2017

AbstractA main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis.
IGF-1 potentiates sensory innervation signalling by modulating the mitochondrial fission/fusion balance
Authors: Ding Yuan , Li Jianmin , Liu Zhen , Liu Huaxiang , Li Hao , Li Zhenzhong 
Published: March 2017

AbstractRestoring the contractile function of long-term denervated skeletal muscle (SKM) cells is difficult due to the long period of denervation, which causes a loss of contractility. Although sensory innervation is considered a promising protective approach, its effect is still restricted. In this study, we introduced insulin-like growth factor-1 (IGF-1) as an efficient protective agent and observed that IGF-1 potentiated the effects of sensory protection by preventing denervated muscle atrophy and improving the condition of denervated muscle cells in vivo and in vitro. IGF-1-induced Akt phosphorylation suppressed the mitochondrial outer-membrane protein Mul1 expression, which is a key step on preserving contractile property of sensory innervated SKM cells. Mul1 overexpression interfered with the balance between mitochondrial fusion and fission and was a key node for blocking the effects of IGF-1 that preserved the contractility of sensory-innervated SKM cells. Activation of AMP-activated protein kinase α (AMPKα), a mitochondrial downstream target, could block the effects of IGF-1. These data provide novel evidence that might be applied when searching for new approaches to improve the functional condition of long-term denervated SKM cells by increasing sensory protection using the IGF-1 signalling system to modulate the balance between mitochondrial fusion and fission.
MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
Authors: Vanhoutte Laetitia , Guilbaud Céline , Martherus Ruben , Bouzin Caroline , Gallez Bernard , Dessy Chantal , Balligand Jean-Luc , Moniotte Stéphane , Feron Olivier 
Published: March 2017

AbstractThe cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8–12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy.
Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds
Authors: Badosa Anna , Frisch Dagmar , Green Andy J. , Rico Ciro , Gómez Africa 
Published: March 2017

AbstractUnderstanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.