bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-Induced MicroRNA-20a Expression Increases ERK Phosphorylation and Angiogenic Gene Expression in Endometriotic Stromal Cells
Authors: Lin Shih-Chieh , Wang Chih-Chuan , Wu Meng-Hsing , Yang Shang-Hsun , Li Yo-Hua , Tsai Shaw-Jenq 
Published: May 2012

Abstract

Context:
Aberrant activation of MAPK has been implicated to play important roles in pathological processes of endometriosis. However, how MAPK are constitutively activated in endometriotic tissues remains largely unknown. microRNA are small noncoding RNA that regulate the stability or translational efficiency of target mRNA by interacting with the 3′ untranslated region. Thus, miRNA are thought to be modulators of the transcriptional response, fine-tuning gene expression.

Objective:
The aim of this study was to evaluate the functional roles of microRNA-20a (miR20a) in MAPK activation and the pathogenesis of endometriosis.

Design:
miR20a expression was analyzed in nonpaired (endometrium = 17; endometriosis = 37) and paired (n = 12) endometriotic tissues by quantitative RT-PCR. Overexpression of miR20a in eutopic endometrial stromal cells or inhibition of miR20a in ectopic endometriotic stromal cells was used to evaluate its impact on ERK phosphorylation and subsequently angiogenesis- and proliferation-related gene expression.

Results:
Levels of miR20a were up-regulated in endometriotic stromal cells. Elevation of miR20a was up-regulated by hypoxia inducible factor-1α. The up-regulation of miR20a causes the down-regulation of dual-specificity phosphatase-2, which leads to prolonged ERK phosphorylation and an increase in the expression of several angiogenic genes. Furthermore, the up-regulation of miR20a enhances the prostaglandin E2-induced expression of fibroblast growth factor-9, a potent mitogen that stimulates both endothelial and endometrial cell proliferation.

Conclusion:
Our findings provide the novel mechanism that not only functionally links together hypoxic stress, miR20a expression, aberrant ERK phosphorylation, and angiogenesis but also demonstrates that miR20a is an important modulator in the development of endometriosis.
The Risk of All-Cause Mortality Is Inversely Related to Serum 25(OH)D Levels
Authors: Saliba Walid , Barnett Ofra , Rennert Hedy S. , Rennert Gad 
Published: May 2012

Abstract

Context and Objectives:
Vitamin D plays a key role in maintaining bone health, but evidence for its nonskeletal effects is inconsistent. This study aims to examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and all-cause mortality in a large general population cohort.

Design, Participants, and Setting:
Using the computerized database of the largest health care provider in Israel, we identified a cohort of subjects 20 years old or older with serum 25(OH)D levels measured between January 2008 and December 2009. Vital status was ascertained through August 2011.

Results:
Median follow-up was 28.5 months (interquartile range 23.8–33.5 months); 7,247 of 182,152 participants (4.0%) died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8 ± 24.2 nmol/liter) than those alive at the end of follow-up (51.0 ± 23.2 nmol/liter), P &lt; 0.001. After adjustment for age, gender, ethnicity, and seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 [95% confidence interval (CI) 1.89–2.15] for the lowest serum 25(OH)D quartile (&lt;33.8 nmol/liter) compared with the highest. After further adjustment for comorbidity, use of vitamin D supplements and statins, smoking, socioeconomic status, and body mass index, the HR was 1.81 (95% CI 1.69–1.95). This remained, even after adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium level (corrected for serum albumin levels), and glomerular filtration rate, 1.85 (95% CI 1.70–2.01). The fully adjusted HR associated with being in the second 25(OH)D quartile (33.8–49.4 nmol/liter) was 1.25 (95% CI 1.16–1.34).

Conclusions:
All-cause mortality is independently and inversely associated with serum 25(OH)D levels at levels less than 50 nmol/liter.
Bypassing the Greatwall–Endosulfine Pathway: Plasticity of a Pivotal Cell-Cycle Regulatory Module in Drosophila melanogaster and Caenorhabditis elegans
Authors: Kim Min-Young , Bucciarelli Elisabetta , Morton Diane G , Williams Byron C , Blake-Hodek Kristina , Pellacani Claudia , Von Stetina Jessica R , Hu Xiaoqian , Somma Maria Patrizia , Drummond-Barbosa Daniela , Goldberg Michael L 
Published: May 2012

Abstract
In vertebrates, mitotic and meiotic M phase is facilitated by the kinase Greatwall (Gwl), which phosphorylates a conserved sequence in the effector Endosulfine (Endos). Phosphorylated Endos inactivates the phosphatase PP2A/B55 to stabilize M-phase-specific phosphorylations added to many proteins by cyclin-dependent kinases (CDKs). We show here that this module functions essentially identically in Drosophila melanogaster and is necessary for proper mitotic and meiotic cell division in a wide variety of tissues. Despite the importance and evolutionary conservation of this pathway between insects and vertebrates, it can be bypassed in at least two situations. First, heterozygosity for loss-of-function mutations of twins, which encodes the Drosophila B55 protein, suppresses the effects of endos or gwl mutations. Several types of cell division occur normally in twins heterozygotes in the complete absence of Endos or the near absence of Gwl. Second, this module is nonessential in the nematode Caenorhaditis elegans. The worm genome does not contain an obvious ortholog of gwl, although it encodes a single Endos protein with a surprisingly well-conserved Gwl target site. Deletion of this site from worm Endos has no obvious effects on cell divisions involved in viability or reproduction under normal laboratory conditions. In contrast to these situations, removal of one copy of twins does not completely bypass the requirement for endos or gwl for Drosophila female fertility, although reducing twins dosage reverses the meiotic maturation defects of hypomorphic gwl mutants. These results have interesting implications for the function and evolution of the mechanisms modulating removal of CDK-directed phosphorylations.
Nucleolar Dominance of the Y Chromosome in Drosophila melanogaster
Authors: Greil Frauke , Ahmad Kami 
Published: May 2012

Abstract
The rDNA genes are transcribed by RNA polymerase I to make structural RNAs for ribosomes. Hundreds of rDNA genes are typically arranged in an array that spans megabase pairs of DNA. These arrays are the major sites of transcription in growing cells, accounting for as much as 50% of RNA synthesis. The repetitive rDNA arrays are thought to use heterochromatic gene silencing as a mechanism for metabolic regulation, since repeated sequences nucleate heterochromatin formation in eukaryotes. Drosophila melanogaster carries an rDNA array on the X chromosome and on the Y chromosome, and genetic analysis has suggested that both are transcribed. However, using a chromatin-marking assay, we find that the entire X chromosome rDNA array is normally silenced in D. melanogaster males, while the Y chromosome rDNA array is dominant and expressed. This resembles “nucleolar dominance,” a phenomenon that occurs in interspecific hybrids where an rDNA array from one parental species is silenced, and that from the other parent is preferentially transcribed. Interspecies nucleolar dominance is thought to result from incompatibilities between species-specific transcription factors and the rDNA promoters in the hybrid, but our results show that nucleolar dominance is a normal feature of rDNA regulation. Nucleolar dominance within D. melanogaster is only partially dependent on known components of heterochromatic gene silencing, implying that a distinctive chromatin regulatory system may act at rDNA genes. Finally, we isolate variant Y chromosomes that allow X chromosome array expression and suggest that the large-scale organization of rDNA arrays contribute to nucleolar dominance. This is the first example of allelic inactivation in D. melanogaster.
Translating stem cell research to the clinic: A constant crosstalk between basic and applied research
Authors: Raineteau Olivier 
Published: May 2012

AbstractPluripotent stem cells hold great promise for the generation of patient-specific cells for disease modeling and regenerative medicine. Focusing on a recent study reporting the successful generation of midbrain dopaminergic neurons and their efficient grafting in animal models of Parkinson’s disease, I discuss how crosstalk between basic and applied stem cell research more generally paves the road toward clinical translation.
Repetitive transcanial magnetic stimulation (RTMS) modulates event-related potential (ERP) indices of attention in autism
Authors: Casanova Manuel , Baruth Joshua , El-Baz Ayman , Tasman Allan , Sears Lonnie , Sokhadze Estate 
Published: May 2012

AbstractIndividuals with autism spectrum disorder (ASD) have previously been shown to have significantly augmented and prolonged event-related potentials (ERP) to irrelevant visual stimuli compared to controls at both early and later stages (e.g., N200, P300) of visual processing and evidence of an overall lack of stimulus discrimination. Abnormally large and indiscriminative cortical responses to sensory stimuli may reflect cortical inhibitory deficits and a disruption in the excitation/inhibition ratio. Low-frequency (≤ 1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. It was our prediction that after 12 sessions of low-frequency rTMS applied bilaterally to the dorsolateral prefrontal cortices in individuals with ASD there would be a significant improvement in ERP indices of selective attention evoked at later (i.e., 200–600 ms) stages of attentional processing as well as an improvement in motor response error rate. We assessed 25 participants with ASD in a task of selective attention using illusory figures before and after 12 sessions of rTMS in a controlled design where a waiting-list group of 20 children with ASD performed the same task twice. We found a significant improvement in both N200 and P300 components as a result of rTMS as well as a significant reduction in response errors. We also found significant reductions in both repetitive behavior and irritability according to clinical behavioral questionnaires as a result of rTMS. We propose that rTMS has the potential to become an important therapeutic tool in ASD research and treatment.
The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses
Authors: Sibilano Riccardo , Frossi Barbara , Calvaruso Marco , Danelli Luca , Betto Elena , Dall’Agnese Alessandra , Tripodo Claudio , Colombo Mario P. , Pucillo Carlo E. , Gri Giorgia 
Published: May 2012

Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.
The Endothelial Antigen ESAM Monitors Hematopoietic Stem Cell Status between Quiescence and Self-Renewal
Authors: Sudo Takao , Yokota Takafumi , Oritani Kenji , Satoh Yusuke , Sugiyama Tatsuki , Ishida Tatsuro , Shibayama Hirohiko , Ezoe Sachiko , Fujita Natsuko , Tanaka Hirokazu , Maeda Tetsuo , Nagasawa Takashi , Kanakura Yuzuru 
Published: May 2012

Abstract
Whereas most hematopoietic stem cells (HSC) are quiescent in homeostasis, they actively proliferate in response to bone marrow (BM) injury. Signals from the BM microenvironment are thought to promote entry of HSC into the cell cycle. However, it has been cumbersome to assess cycle status of viable HSC and thus explore unique features associated with division. In this study, we show that expression of endothelial cell-selective adhesion molecule (ESAM) can be a powerful indicator of HSC activation. ESAM levels clearly mirrored the shift of HSC between quiescence and activation, and it was prominent in comparison with other HSC-related Ags. ESAMhi HSC were actively dividing, but had surprisingly high long-term reconstituting capacity. Immunohistochemical analyses showed that most ESAMhi HSC were located near vascular endothelium in the BM after 5-fluorouracil treatment. To determine the importance of ESAM in the process of BM recovery, ESAM knockout mice were treated with 5-fluorouracil and their hematopoietic reconstruction was examined. The ESAM deficiency caused severe and prolonged BM suppression, suggesting that ESAM is functionally indispensable for HSC to re-establish homeostatic hematopoiesis. With respect to intracellular regulators, NF-κB and topoisomerase II levels correlated with the ESAM upregulation. Thus, our data demonstrate that the intensity of ESAM expression is useful to trace activated HSC and to understand molecular events involved in stem cell states.
CD8+ T Cells Suppress Viral Replication in the Cornea but Contribute to VEGF-C–Induced Lymphatic Vessel Genesis
Authors: Conrady Christopher D. , Zheng Min , Stone Donald U. , Carr Daniel J. J. 
Published: May 2012

Abstract
HSV-1 is the leading cause of infectious corneal blindness in the industrialized world. CD4+ T cells are thought to be the major leukocyte population mediating immunity to HSV-1 in the cornea as well as the likely source of immunopathology that reduces visual acuity. However, the role of CD8+ T cells in immune surveillance of the cornea is unclear. Thus, we sought to evaluate the role of CD8+ T cells in ocular immunity using transgenic mice in which &gt;98% of CD8+ T cells are specific for the immunodominant HSV-1 epitope (gBT-I.1). We found a significant reduction in virus, elevation in HSV-specific CD8+ T cell influx, and more CD8+ T cells expressing CXCR3 in the cornea of transgenic mice compared with those in the cornea of wild-type controls yet similar acute corneal pathology. However, by day 30 postinfection, wild-type mice had drastically more blood and lymphatic vessel projections into the cornea compared with gBT-I.1 mice, in which only lymphatic vessel growth in response to VEGF-C could be appreciated. Taken together, these results show that CD8+ T cells are required to eliminate virus more efficiently from the cornea but play a minimal role in immunopathology as a source of VEGF-C.
Relative Contributions of Dectin-1 and Complement to Immune Responses to Particulate β-Glucans
Authors: Huang Haibin , Ostroff Gary R. , Lee Chrono K. , Agarwal Sarika , Ram Sanjay , Rice Peter A. , Specht Charles A. , Levitz Stuart M. 
Published: May 2012

Abstract
Glucan particles (GPs) are Saccharomyces cerevisiae cell walls chemically extracted so they are composed primarily of particulate β-1,3-d-glucans. GPs are recognized by Dectin-1 and are potent complement activators. Mice immunized with Ag-loaded GPs develop robust Ab and CD4+ T cell responses. In this study, we examined the relative contributions of Dectin-1 and complement to GP phagocytosis and Ag-specific responses to immunization with OVA encapsulated in GPs. The in vitro phagocytosis of GPs by bone marrow-derived dendritic cells was facilitated by heat-labile serum component(s) independently of Dectin-1. This enhanced uptake was not seen with serum from complement component 3 knockout (C3−/−) mice and was also inhibited by blocking Abs directed against complement receptor 3. After i.p. injection, percent phagocytosis of GPs by peritoneal macrophages was comparable in wild-type and Dectin-1−/− mice and was not inhibited by the soluble β-glucan antagonist laminarin. In contrast, a much lower percentage of peritoneal macrophages from C3−/− mice phagocytosed GPs, and this percentage was further reduced in the presence of laminarin. Subcutaneous immunization of wild-type, Dectin-1−/−, and C3−/− mice with GP-OVA resulted in similar Ag-specific IgG1 and IgG2c type Ab and CD4+ T cell lymphoproliferative responses. Moreover, while CD4+ Th1 and Th2 responses measured by ELISPOT assay were similar in the three mouse strains, Th17 responses were reduced in C3−/− mice. Thus, although Dectin-1 is necessary for optimal phagocytosis of GPs in the absence of complement, complement dominates when both an intact complement system and Dectin-1 are present. In addition, Th-skewing after GP-based immunization was altered in C3−/− mice.
The Neoliberal Phoenix: The Big Society or Business as Usual
Authors: Bone John D. 
Published: May 2012

At present something curious appears to be occurring in the UK in the aftermath of the ‘credit crunch’, with respect to the political, economic and social complexion of the policies currently being implemented by the Coalition government, and not least in terms of the manner in which they are being introduced. Specifically, as this paper argues, despite a degree of rhetoric to the contrary, asserting a movement towards a more socially ‘progressive’ and inclusive ‘Big Society’, the current policy framework appears quite clearly to have been framed from a radical neoliberal perspective, to the extent that much of what is being implemented and proposed bears more than a passing resemblance to the neoliberal Structural Adjustment Programmes imposed by the IMF and World Bank on developing economies since the 1970s. This paper suggests that the implementation of the Big Society agenda - while seeming earnestly advocated by its presumed architect Philip Blond (whose Red Toryism has been cited as providing the intellectual foundation for the project, much as Giddens’ Third Way informed ‘Blairism’) - may have implications that are largely oppositional to its asserted aims. Such initiatives can be considered, in their application at least, as potentially legitimating discourses for the advancing of neoliberal policies against the background of an increasingly uneasy populace. In this vein, the Big Society, as the latest variant of such socio-economic visions, can easily be construed as being little more than a convenient vehicle, employed to rehabilitate and further entrench neoliberalism in the aftermath of its self induced crisis. This view is supported by the observation that a key feature of the Big Society agenda, in practice, appears to be the increasing marketisation of the public realm and, crucially, dismantling the ‘Big (Welfare) State’, where the latter, in almost Orwellian fashion, is now being indicted for many of the social and economic ills that the ‘free market’ era has delivered.
Comparison of Long-Term Variability of Retinal Nerve Fiber Layer Measurements Made with the RTVue OCT and Scanning Laser Polarimetry
Authors: Naghizadeh Farzaneh , Garas Anita , Vargha Péter , Holló Gábor 
Published: May 2012

Purpose. To compare long-term variability of retinal nerve fiber layer thickness (RNFLT) measurements made with the RTVue-100 Fourier-domain optical coherence tomograph (RTVue-OCT) and scanning laser polarimetry with variable (GDx-VCC) and enhanced (GDx-ECC) corneal compensation. Methods. One eye each of 110 Caucasian patients (17 healthy, 20 ocular hypertensive, 22 preperimetric, and 51 perimetric glaucoma eyes, of which 10 showed visual field progression) were imaged prospectively at 6-month intervals for 1.5 to 3 years. Results. Median change of Octopus visual field mean defect was −0.300 dB/y for the controls, −0.120 dB/y for perimetric glaucoma group, and 1.231 dB/y for the 10 functionally progressing perimetric glaucoma eyes. Relative (%) variance of all RNFLT parameters measured with RTVue-OCT was significantly (p<<0.001) smaller than that with both of the GDx methods. Relative RNFLT progression slopes (% change/y) did not differ significantly between the methods. Relative variance of the RNFLT parameters did not differ between the control and perimetric glaucoma group with RTVue-OCT, but for most parameters it was consistently higher for perimetric glaucoma with both GDx methods (p≤0.01). Relative RNFLT progression slopes, however, did not separate the control and perimetric glaucoma eyes with either method. Conclusions. Long-term RNFLT measurements are less variable with the RTVue-OCT than with GDx-VCC and GDx-ECC. Long-term measurement variability is higher in perimetric glaucoma than in healthy eyes with both GDx methods, but no similar between-group difference is seen with RTvue-OCT. None of the tested methods separated the rate of progression between healthy and well-controlled perimetric glaucoma eyes in 1.5 to 3 years follow-up.
Optical Absorption Enhancement in Freestanding GaAs Thin Film Nanopyramid Arrays
Authors: Liang Dong , Huo Yijie , Kang Yangsen , Wang Ken Xingze , Gu Anjia , Tan Meiyueh , Yu Zongfu , Li Shuang , Jia Jieyang , Bao Xinyu , Wang Shuang , Yao Yan , Wong H.‐S. Philip , Fan Shanhui , Cui Yi , Harris James S. 
Published: May 2012

AbstractAlthough III–V compound semiconductor multi‐junction cells show the highest efficiency among all types of solar cells, their cost is quite high due to expensive substrates, long epitaxial growth and complex balance of system components. To reduce the cost, ultra‐thin films with advanced light management are desired. Here effective light trapping in freestanding thin film nanopyramid arrays is demonstrated and multiple‐times light path enhancement is realized, where only 160 nm thick GaAs with nanopyramid structures is equivalent to a 1 μm thick planar film. The GaAs nanopyramids are fabricated using a combination of nanosphere lithography, nanopyramid metal organic chemical vapor deposition (MOCVD) growth, and gas‐phase substrate removal processes. Excellent optical absorption is demonstrated over a broad range of wavelengths, at various incident angles and at large‐curvature bending. Compared to an equally thick planar control film, the overall number of photons absorbed is increased by about 100% at various incident angles due to significant antireflection and light trapping effects. By implementing these nanopyramid structures, III–V material usage and deposition time can be significantly reduced to produce high‐efficiency, low‐cost thin film III–V solar cells.