bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential microRNA expression in blood in multiple sclerosis
Authors: Søndergaard Helle Bach , Hesse Dan , Krakauer Martin , Sørensen Per Soelberg , Sellebjerg Finn 
Published: June 2013

Background: microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged. Objective: We assessed whether miRNAs contribute to the altered immune activation state in relapsing–remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS). Methods: We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation. Results: We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively). Conclusions: RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.
Perivenular brain lesions in a primate multiple sclerosis model at 7-tesla magnetic resonance imaging
Authors: Gaitán María I , Maggi Pietro , Wohler Jillian , Leibovitch Emily , Sati Pascal , Calandri Ismael L , Merkle Hellmut , Massacesi Luca , Silva Afonso C , Jacobson Steven , Reich Daniel S 
Published: June 2013

Background Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time – a perspective not obtainable with postmortem histopathology. Relapsing–remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter (WM) lesions similar to those observed in MS. Methods Brain lesion development and evolution were studied in vivo and postmortem in four marmosets with EAE through serial T2- and T2*-weighted scans at 7-tesla. Supratentorial WM lesions were identified and characterized. Results Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles. Conclusion As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.
The CLOSER survey: Impact of postmenopausal vaginal discomfort on women and male partners in the UK
Authors: Domoney Claudine , Currie Heather , Panay Nick , Maamari Ricardo , Nappi Rossella E 
Published: June 2013

Objective To understand the physical and emotional impact of postmenopausal vaginal discomfort on relationships between women and their male partners. Study design In a quantitative, Internet-based survey, 8200 individuals from the UK, Denmark, Sweden, Norway, Finland, France, Italy, US and Canada (postmenopausal, married/cohabiting women, aged 55–65 years, who had experienced vaginal discomfort, and male partners of such women) completed a structured questionnaire. Main outcome measures Results for respondents from the UK (500 men, 500 women), expressed as percentages of women/men describing particular answers, are reported. Results Avoiding physical intimacy because of vaginal discomfort was reported by 69% of women and 76% of male partners, mainly due to concern about sex being painful (women 63%; men 61%); 18% of women considered vaginal discomfort had created emotional distance between them and their partners. Local estrogen treatment was used by 21% of women, among whom 58% subsequently reported less painful sex. Following such treatment, 33% of women and 30% of male partners reported an improved sex life, while 33% of women and 34% of male partners described becoming emotionally closer. Although 73% of women did not consider enough information about vaginal discomfort to be available, 60% would consult a physician to obtain this. Conclusions Although vaginal discomfort has a substantial impact on postmenopausal women and their partners, improvements in sexual and emotional relationships can follow use of local estrogen therapy. Not all women may be aware of therapeutic options; healthcare providers can improve outcomes by more openly communicating and initiating discussion with patients.
Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P)
Authors: Zhang Lin , Urtz Nicole , Gaertner Florian , Legate Kyle R. , Petzold Tobias , Lorenz Michael , Mazharian Alexandra , Watson Steve P. , Massberg Steffen 
Published: June 2013

Key Points
Sphk2 provides a source of intracellular S1P that tightly controls thrombopoiesis by regulating SFK expression and activity in MKs. Modulation of intracellular S1P by regulating Sphk2 may provide a new strategy to enhance platelet production in patients with thrombocytopenia.
CX3CR1 reduces Ly6Chigh-monocyte motility within and release from the bone marrow after chemotherapy in mice
Authors: Jacquelin Sébastien , Licata Fabrice , Dorgham Karim , Hermand Patricia , Poupel Lucie , Guyon Elodie , Deterre Philippe , Hume David A. , Combadière Christophe , Boissonnas Alexandre 
Published: June 2013

Key PointsCX3CR1 mediates monocyte retention in the bone marrow. Myelorestoration after chemotherapy is controlled by chemokine receptors.
Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results
Authors: Gay Francesca , Magarotto Valeria , Crippa Claudia , Pescosta Norbert , Guglielmelli Tommasina , Cavallo Federica , Pezzatti Sara , Ferrari Samantha , Liberati Anna Marina , Oliva Stefania , Patriarca Francesca , Offidani Massimo , Omedé Paola , Montefusco Vittorio , Petrucci Maria Teresa , Giuliani Nicola , Passera Roberto , Pietrantuono Giuseppe , Boccadoro Mario , Corradini Paolo , Palumbo Antonio 
Published: June 2013

Key Points
Bortezomib-induction/Mel100-ASCT/lenalidomide consolidation-maintenance is effective in elderly patients with excellent performance status. Deaths related to AEs were higher in patients ≥70 years, suggesting the need of a more careful patient selection.
HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10
Authors: Takahashi Masahiko , Higuchi Masaya , Makokha Grace Naswa , Matsuki Hideaki , Yoshita Manami , Tanaka Yuetsu , Fujii Masahiro 
Published: June 2013

Key PointsInteraction of HTLV-1 Tax with USP10 reduces arsenic-induced stress granule formation and enhances ROS production. USP10 controls sensitivities of leukemia cell lines to arsenic-induced apoptosis.
Tc-knirps plays different roles in the specification of antennal and mandibular parasegment boundaries and is regulated by a pair-rule gene in the beetle Tribolium castaneum
Authors: Peel Andrew D , Schanda Julia , Grossmann Daniela , Ruge Frank , Oberhofer Georg , Gilles Anna F , Schinko Johannes B , Klingler Martin , Bucher Gregor 
Published: June 2013

Abstract

Background
The Drosophila larval head is evolutionarily derived at the genetic and morphological level. In the beetle Tribolium castaneum, development of the larval head more closely resembles the ancestral arthropod condition. Unlike in Drosophila, a knirps homologue (Tc-kni) is required for development of the antennae and mandibles. However, published Tc-kni data are restricted to cuticle phenotypes and Tc-even-skipped and Tc-wingless stainings in knockdown embryos. Hence, it has remained unclear whether the entire antennal and mandibular segments depend on Tc-kni function, and whether the intervening intercalary segment is formed completely. We address these questions with a detailed examination of Tc-kni function.

Results
By examining the expression of marker genes in RNAi embryos, we show that Tc-kni is required only for the formation of the posterior parts of the antennal and mandibular segments (i.e. the parasegmental boundaries). Moreover, we find that the role of Tc-kni is distinct in these segments: Tc-kni is required for the initiation of the antennal parasegment boundary, but only for the maintenance of the mandibular parasegmental boundary. Surprisingly, Tc-kni controls the timing of expression of the Hox gene Tc-labial in the intercalary segment, although this segment does form in the absence of Tc-kni function. Unexpectedly, we find that the pair-rule gene Tc-even-skipped helps set the posterior boundary of Tc-kni expression in the mandible. Using the mutant antennaless, a likely regulatory Null mutation at the Tc-kni locus, we provide evidence that our RNAi studies represent a Null situation.

Conclusions

Tc-kni is required for the initiation of the antennal and the maintenance of the mandibular parasegmental boundaries. Tc-kni is not required for specification of the anterior regions of these segments, nor the intervening intercalary segment, confirming that Tc-kni is not a canonical ‘gap-gene’. Our finding that a gap gene orthologue is regulated by a pair rule gene adds to the view that the segmentation gene hierarchies differ between Tribolium and Drosophila upstream of the pair rule gene level. In Tribolium, as in Drosophila, head and trunk segmentation gene networks cooperate to pattern the mandibular segment, albeit involving Tc-kni as novel component.
Cubilin expression is monoallelic and epigenetically augmented via PPARs
Authors: Aseem Obaidullah , Barth Jeremy L , Klatt Sandra C , Smith Brian T , Argraves W Scott 
Published: June 2013

Abstract

Background
Cubilin is an endocytic receptor that is necessary for renal and intestinal absorption of a range of ligands. Endocytosis mediated by cubilin and its co-receptor megalin is the principal mechanism for proximal tubule reabsorption of proteins from the glomerular filtrate. Cubilin is also required for intestinal endocytosis of intrinsic factor-vitamin B12 complex. Despite its importance, little is known about the regulation of cubilin expression.

Results
Here we show that cubilin expression is under epigenetic regulation by at least two processes. The first process involves inactivation of expression of one of the cubilin alleles. This monoallelic expression state could not be transformed to biallelic by inhibiting DNA methylation or histone deacetylation. The second process involves transcriptional regulation of cubilin by peroxisome proliferator-activated receptor (PPAR) transcription factors that are themselves regulated by DNA methylation and histone deacetylation. This is supported by findings that inhibitors of DNA methylation and histone deacetylation, 5Aza and TSA, increase cubilin mRNA and protein in renal and intestinal cell lines. Not only was the expression of PPARα and γ inducible by 5Aza and TSA, but the positive effects of TSA and 5Aza on cubilin expression were also dependent on both increased PPAR transcription and activation. Additionally, 5Aza and TSA had similar effects on the expression of the cubilin co-receptor, megalin.

Conclusions
Together, these findings reveal that cubilin and megalin mRNA expression is under epigenetic control and thus point to new avenues for overcoming pathological suppression of these genes through targeting of epigenetic regulatory processes.
Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase
Authors: Dong Haiyun , Li Jinxiu , Lv Youdi , Zhou Yanyan , Wang Guyi , Hu Shuang , He Xiaoyu , Yang Ping , Zhou Zhiguang , Xiang Xudong , Wang Cong-Yi 
Published: June 2013

Abstract

Background
Despite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking.

Methods
Recent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery.

Results
135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase.

Conclusions
Given the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.
Polymyxin P is the active principle in suppressing phytopathogenic Erwinia spp. by the biocontrol rhizobacterium Paenibacillus polymyxa M-1
Authors: Niu Ben , Vater Joachim , Rueckert Christian , Blom Jochen , Lehmann Maik , Ru Jin-Jiang , Chen Xiao-Hua , Wang Qi , Borriss Rainer 
Published: June 2013

Abstract

Background
Nine gene clusters dedicated to nonribosomal synthesis of secondary metabolites with possible antimicrobial action, including polymyxin and fusaricidin, were detected within the whole genome sequence of the plant growth-promoting rhizobacterium (PGPR) Paenibacillus polymyxa M-1. To survey the antimicrobial compounds expressed by M-1 we analyzed the active principle suppressing phytopathogenic Erwinia spp.

Results

P. polymyxa M-1 suppressed the growth of phytopathogenic Erwinia amylovora Ea 273, and E. carotovora, the causative agents of fire blight and soft rot, respectively. By MALDI-TOF mass spectrometry and reversed-phase high-performance liquid chromatography (RP-HPLC), two antibacterial compounds bearing molecular masses of 1190.9 Da and 1176.9 Da were detected as being the two components of polymyxin P, polymyxin P1 and P2, respectively. The active principle acting against the two Erwinia strains was isolated from TLC plates and identified by postsource decay (PSD)-MALDI-TOF mass spectrometry as polymyxin P1 and polymyxin P2. These findings were corroborated by domain structure analysis of the polymyxin (pmx) gene cluster detected in the M-1 chromosome which revealed that corresponding to the chemical structure of polymyxin P, the gene cluster is encoding D-Phe in position 6 and L-Thr in position 7.

Conclusions
Identical morphological changes in the cell wall of the bacterial phytopathogens treated with either crude polymyxin P or culture supernatant of M-1 corroborated that polymyxin P is the main component of the biocontrol effect exerted by strain M-1 against phytopathogenic Erwinia spp.
Quantitative expression analysis and prognostic significance of the BCL2-associated Xgene in nasopharyngeal carcinoma: a retrospective cohort study
Authors: Kontos Christos K , Fendri Ali , Khabir Abdelmajid , Mokdad-Gargouri Raja , Scorilas Andreas 
Published: June 2013

AbstractBackgroundNasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. TheBCL2-associated X(BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. We have recently shown thatBCL2andBCL2L12, two other members of the same apoptosis-related family, possess significant prognostic value in NPC. The objective of the current study was to analyzeBAXmRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease.MethodsTotal RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA,BAXmRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method.ResultsLowerBAXmRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples.BAXmRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients withBAXmRNA-positive NPC have significantly longer disease-free survival (DFS) and overall survival (OS). In accordance with these findings, Cox regression analysis revealed thatBAXmRNA expression can be considered as a favorable prognostic indicator of DFS and OS in NPC, independent of their gender, age, tumor histology, tumor extent, and nodal status. Furthermore, NPC patients without distant metastases are less likely to relapse when their primary tumor isBAXmRNA-positive, compared to metastasis-free patients with aBAX-negative nasopharyngeal malignancy.ConclusionThis is the first study examining the potential clinical utility ofBAXas a prognostic tumor biomarker in NPC. We provide evidence thatBAXmRNA expression can be considered as an independent favorable prognostic indicator of DFS and OS in NPC.
Antithrombotic and antiplatelet activities of Soshiho-tang extract
Authors: Lee Jung-Jin , Kim Taesoo , Cho Won-Kyung , Ma Jin Yeul 
Published: June 2013

Abstract

Background
Soshiho-tang (SH; Chinese name, Xiao-Chai-Hu-Tang; Japanese name, Shosaiko-to) is a traditional Korean, Chinese, and Japanese medicine, which has been used to treat various conditions, including hepatitis, liver cirrhosis, and chronic and acute liver disease. SH consists of seven herbal components, of which Scutellaria baicalensis Georgi and Zingiber officinale Roscoe, are reported to have antithrombotic and antiplatelet activities. We investigated the antithrombotic activity of SH, including S. baicalensis and Z. officinale, as an integrative therapy.

Methods
To identify the antithrombotic activity of SH, we used a FeCl3-induced thrombus formation model. The mechanism of SH-mediated antithrombotic activity was assessed by determining platelet aggregation and coagulation times ex vivo, washed platelet aggregation, serotonin secretion, and thromboxane B2 formation.

Results
SH prolonged the occlusion time of thrombus formation when applied in a FeCl3-induced thrombus formation model. SH also inhibited collagen-induced platelet aggregation ex vivo in a concentration-dependent manner; however, it did not affect coagulation. Hence, to identify the antiplatelet effect of SH, we investigated washed platelet aggregations in vitro. SH significantly inhibited various agonist-induced platelet aggregations, and it completely inhibited serotonin secretion and thromboxane B2 formation.

Conclusions
The findings suggest that SH inhibited FeCl3-induced thrombus formation through antiplatelet activity, including inhibition of platelet aggregation, and serotonin and TXB2 production. Thus, SH may be useful as an integrative herbal formula for the treatment of thrombosis.
Effect of black tea extract on herpes simplex virus-1 infection of cultured cells
Authors: Cantatore Anthony , Randall Sade D , Traum Daniel , Adams Sandra D 
Published: June 2013

Abstract

Background
The purpose of this investigation was to determine if black tea extract (BTE), consisting primarily of flavanol compounds called theaflavins, could inhibit herpes simplex virus type-1 (HSV-1) infection in cultured A549 (human epithelial) and Vero cells.

Methods
The effect of BTE both on A549 and Vero cultured cells and on HSV-1 was assessed by using phase contrast and fluorescent microscopy, and cell viability and proliferation assays. After establishing the maximum non-cytotoxic concentration of BTE, A549 and Vero cells and HSV-1 virions were treated with varying concentrations of BTE, respectively. A549 and Vero cells were infected with HSV-1 with green fluorescent protein (GFP) insert at the UL46 gene. The effect of infectivity was determined by viral DNA extraction followed by PCR, plaque assays, adsorption assays, and electrophoresis of PCR products.

Results
BTE was not cytotoxic to A549 and Vero cells, as confirmed by cell viability and proliferation assays, in which BTE treated groups paralleled the positive control group. For both cell lines, plaque assays and fluorescent microscopy indicated an inverse relationship between BTE concentration (from 0.14 μM – 1.4 mM) and HSV-1 infectivity. Specifically, PCR and electrophoresis showed a reduction in the viral genome following treatment with BTE. In addition, there was a noticeable decrease in the amount of viral plaques for BTE treated samples in the adsorption assays.

Conclusions
BTE consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles. These findings indicate that BTE enriched with theaflavins has the potential to be developed as a safe, therapeutic antiviral agent to prevent the spread of HSV-1.
Heat stress-induced response of the proteomes of leaves from Salvia splendens Vista and King
Authors: Liu Hui , Shen Guozheng , Fang Xianping , Fu Qiaojuan , Huang Kangkang , Chen Yi , Yu Hong , Zhao Yun , Zhang Le , Jin Liang , Ruan Songlin 
Published: June 2013

Abstract

Background

Salvia splendens Ker-Gawl, most commonly used in China to add a splash of brilliant color to the surroundings during the warm season, is subject to heat stress, which can greatly affect its growth and yield.

Results
To gain a comprehensive understanding of heat-tolerance mechanisms of S. splendens, we assessed the heat-stress responses and characterized the proteomes of leaves from two varieties, Vista (heat resistant) and King (heat sensitive). Denaturing two-dimensional gel electrophoresis (2–DE) and tandem mass spectrometry were used to identify heat-responsive proteins. Heat stress induced the reversible inactivation of photosystem II reaction centers and increased the amounts of antioxidative enzymes, thereby decreasing oxidative damage. Vista leaves had a much greater ability than King leaves to develop light-protective and oxygen-scavenging systems in response to heat stress. More than 1213 leaf proteome spots were reproducibly detected in the gels, with a total of 33 proteins in each leaf type differentially regulated when Salvia splendens were heat stress treated. Of these proteins, 23 and 28 from Vista and King, respectively, were identified.

Conclusions
Most of the identified proteins are involved in photosynthesis, metabolism, protein processing, or stress response, indicating that many different processes work together to establish a new cellular homeostasis in response to heat stress.