bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whirlin, a cytoskeletal scaffolding protein, stabilizes the paranodal region and axonal cytoskeleton in myelinated axons
Authors: Green James A , Yang Jun , Grati M’hamed , Kachar Bechara , Bhat Manzoor A 
Published: September 2013

Abstract

Background
Myelinated axons are organized into distinct subcellular and molecular regions. Without proper organization, electrical nerve conduction is delayed, resulting in detrimental physiological outcomes. One such region is the paranode where axo-glial septate junctions act as a molecular fence to separate the sodium (Na+) channel-enriched node from the potassium (K+) channel-enriched juxtaparanode. A significant lack of knowledge remains as to cytoskeletal proteins which stabilize paranodal domains and underlying cytoskeleton. Whirlin (Whrn) is a PDZ domain-containing cytoskeletal scaffold whose absence in humans results in Usher Syndromes or variable deafness-blindness syndromes. Mutant Whirlin (Whrn) mouse model studies have linked such behavioral deficits to improper localization of critical transmembrane protein complexes in the ear and eye. Until now, no reports exist about the function of Whrn in myelinated axons.

Results
RT-PCR and immunoblot analyses revealed expression of Whrn mRNA and Whrn full-length protein, respectively, in several stages of central and peripheral nervous system development. Comparing wild-type mice to Whrn knockout (Whrn

−/−
) mice, we observed no significant differences in the expression of standard axonal domain markers by immunoblot analysis but observed and quantified a novel paranodal compaction phenotype in 4 to 8 week-old Whrn

−/−
nerves. The paranodal compaction phenotype and associated cytoskeletal disruption was observed in Whrn

−/−
mutant sciatic nerves and spinal cord fibers from early (2 week-old) to late (1 year-old) stages of development. Light and electron microscopic analyses of Whrn knockout mice reveal bead-like swellings in cerebellar Purkinje axons containing mitochondria and vesicles by both. These data suggest that Whrn plays a role in proper cytoskeletal organization in myelinated axons.

Conclusions
Domain organization in myelinated axons remains a complex developmental process. Here we demonstrate that loss of Whrn disrupts proper axonal domain organization. Whrn likely contributes to the stabilization of paranodal myelin loops and axonal cytoskeleton through yet unconfirmed cytoskeletal proteins. Paranodal abnormalities are consistently observed throughout development (2 wk-1 yr) and similar between central and peripheral nervous systems. In conclusion, our observations suggest that Whrn is not required for the organization of axonal domains, but once organized, Whrn acts as a cytoskeletal linker to ensure proper paranodal compaction and stabilization of the axonal cytoskeleton in myelinated axons.
Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice
Authors: Ferrazoli Enéas Galdini , Blanco Miriam Marcela , Bittencourt Simone , Bachi André Luis Lacerda , Bahia Luciana , Soares Milena Botelho Pereira , Ribeiro-dos-Santos Ricardo , Mello Luiz Eugênio , Longo Beatriz Monteiro 
Published: September 2013

AbstractBackgroundBone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-α after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells.ResultsBone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels.ConclusionsBone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies.
High-risk human papillomavirus infection is associated with premature rupture of membranes
Authors: Cho GeumJoon , Min Kyung-Jin , Hong Hye-Ri , Kim SuhngWook , Hong Jin-Hwa , Lee Jae-Kwan , Oh Min-Jeong , Kim HaiJoong 
Published: September 2013

AbstractBackgroundHuman papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes.MethodsWe conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum.ResultsThe prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups.ConclusionsWe observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM.
Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer
Authors: Liang Xing-Hua , Li Ling-ling , Wu Geng-Gang , Xie Yi-Cheng , Zhang Guang-Xian , Chen Wei , Yang Hai-Feng , Liu Qi-Long , Li Wen-Hong , He Wen-guang , Huang Yan-Nian , Zeng Xian-Cheng 
Published: September 2013

Abstract

Background
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood.

Methods
In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells.

Results
Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1.

Conclusions
Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.
A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthritis and spondyloarthropathy
Authors: Bhattacharjee Mitali , Sharma Rakesh , Goel Renu , Balakrishnan Lavanya , Renuse Santosh , Advani Jayshree , Gupta Shantal Tankala , Verma Renu , Pinto Sneha M , Sekhar Nirujogi Raja , Nair Bipin , Prasad T S Keshava , Harsha H C , Jois Ramesh , Shankar Subramanian , Pandey Akhilesh 
Published: September 2013

Abstract

Background
Arthritis refers to inflammation of joints and includes common disorders such as rheumatoid arthritis (RA) and spondyloarthropathies (SpAs). These diseases differ mainly in terms of their clinical manifestations and the underlying pathogenesis. Glycoproteins in synovial fluid might reflect the disease activity status in the joints affected by arthritis; yet they have not been systematically studied previously. Although markers have been described for assisting in the diagnosis of RA, there are currently no known biomarkers for SpA.

Materials and methods
We sought to determine the relative abundance of glycoproteins in RA and SpA by lectin affinity chromatography coupled to iTRAQ labeling and LC-MS/MS analysis. We also used ELISA to validate the overexpression of VCAM-1, one of the candidate proteins identified in this study, in synovial fluid from RA patients.

Results and discussion
We identified proteins that were previously reported to be overexpressed in RA including metalloproteinase inhibitor 1 (TIMP1), myeloperoxidase (MPO) and several S100 proteins. In addition, we discovered several novel candidates that were overexpressed in SpA including Apolipoproteins C-II and C-III and the SUN domain-containing protein 3 (SUN3). Novel molecules found overexpressed in RA included extracellular matrix protein 1 (ECM1) and lumican (LUM). We validated one of the candidate biomarkers, vascular cell adhesion molecule 1 (VCAM1), in 20 RA and SpA samples using ELISA and confirmed its overexpression in RA (p-value <0.01). Our quantitative glycoproteomic approach to study arthritic disorders should open up new avenues for additional proteomics-based discovery studies in rheumatological disorders.
The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota
Authors: Dantoft Widad , Davis Monica M , Lindvall Jessica M , Tang Xiongzhuo , Uvell Hanna , Junell Anna , Beskow Anne , Engström Ylva 
Published: September 2013

Abstract

Background
Innate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. Gene activation by potent NF-κB transcription factors is essential both in mammals and Drosophila during infection and stress challenges. If not strictly controlled, this potent defense system can activate autoimmune and inflammatory stress reactions, with deleterious consequences for the organism. Negative regulation to prevent gene activation in healthy organisms, in the presence of the commensal gut flora, is however not well understood.

Results
We show that the Drosophila homolog of mammalian Oct1/POU2F1 transcription factor, called Nubbin (Nub), is a repressor of NF-κB/Relish-driven antimicrobial peptide gene expression in flies. In nub

1
mutants, which lack Nub-PD protein, excessive expression of antimicrobial peptide genes occurs in the absence of infection, leading to a significant reduction of the numbers of cultivatable gut commensal bacteria. This aberrant immune gene expression was effectively blocked by expression of Nub from a transgene. We have identified an upstream regulatory region, containing a cluster of octamer sites, which is required for repression of antimicrobial peptide gene expression in healthy flies. Chromatin immunoprecipitation experiments demonstrated that Nub binds to octamer-containing promoter fragments of several immune genes. Gene expression profiling revealed that Drosophila Nub negatively regulates many genes that are involved in immune and stress responses, while it is a positive regulator of genes involved in differentiation and metabolism.

Conclusions
This study demonstrates that a large number of genes that are activated by NF-κB/Relish in response to infection are normally repressed by the evolutionarily conserved Oct/POU transcription factor Nub. This prevents uncontrolled gene activation and supports the existence of a normal gut flora. We suggest that Nub protein plays an ancient role, shared with mammalian Oct/POU transcription factors, to moderate responses to immune challenge, thereby increasing the tolerance to biotic stress.
The effect of periodontal therapy on C-reactive protein, endothelial function, lipids and proinflammatory biomarkers in patients with stable coronary artery disease: study protocol for a randomized controlled trial
Authors: Saffi Marco Aurélio Lumertz , Furtado Mariana Vargas , Montenegro Márlon Munhoz , Ribeiro Ingrid Webb Josephson , Kampits Cassio , Rabelo-Silva Eneida Rejane , Polanczyk Carisi Anne , Rösing Cassiano Kuchenbecker , Haas Alex Nogueira 
Published: September 2013

Abstract

Background
Scarce information exists regarding the preventive effect of periodontal treatment in the recurrence of cardiovascular events. Prevention may be achieved by targeting risk factors for recurrent coronary artery disease (CAD) in patients with previous history of cardiovascular events. The aim of this trial is to compare the effect of two periodontal treatment approaches on levels of C-reactive protein, lipids, flow-mediated dilation and serum concentrations of proinflammatory and endothelial markers in stable CAD patients with periodontitis over a period of 12 months.

Methods/design
This is a randomized, parallel design, examiner blinded, controlled clinical trial. Individuals from both genders, 35 years of age and older, with concomitant diagnosis of CAD and periodontitis will be included. CAD will be defined as the occurrence of at least one of the following events 6 months prior to entering the trial: documented history of myocardial infarction; surgical or percutaneous myocardial revascularization and lesion >50% in at least one coronary artery assessed by angiography; presence of angina and positive noninvasive testing of ischemia. Diagnosis of periodontitis will be defined using the CDC-AAP case definition (≥2 interproximal sites with clinical attachment loss ≥6 mm and ≥1 interproximal site with probing depth ≥5 mm). Individuals will have to present at least ten teeth present to be included. One hundred individuals will be allocated to test (intensive periodontal treatment comprised by scaling and root planing) or control (community periodontal treatment consisting of one session of supragingival plaque removal only) treatment groups. Full-mouth six sites per tooth periodontal examinations and subgingival biofilm samples will be conducted at baseline, 3, 6 and 12 months after treatment. The primary outcome of this study will be C-reactive protein changes over time. Secondary outcomes include levels of total cholesterol, LDL-C, HDL-C, triglycerides, IL-1β, IL-6, TNFα, fibrinogen, ICAM-1, VCAM-1 and E-selectin. These outcomes will be assessed at all time points over 12 months. Flow-mediated dilation will be assessed at baseline, 1, 3 and 6 months after periodontal therapy.

Discussion
This trial will provide new evidence regarding the effect of periodontal treatment on risk markers for recurrence of cardiovascular events in stable coronary artery disease patients.

Trial registration number
ClinicalTrials.gov Identifier, NCT01609725
Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models
Authors: Capello Michela , Cappello Paola , Linty Federica Caterina , Chiarle Roberto , Sperduti Isabella , Novarino Anna , Salacone Paola , Mandili Giorgia , Naccarati Alessio , Sacerdote Carlotta , Beghelli Stefania , Bersani Samantha , Barbi Stefano , Bassi Claudio , Scarpa Aldo , Nisticò Paola , Giovarelli Mirella , Vineis Paolo , Milella Michele , Novelli Francesco 
Published: September 2013

Abstract

Background
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with only a 5% 5-year survival rate. Reliable biomarkers for early detection are still lacking. The goals of this study were (a) to identify early humoral responses in genetically engineered mice (GEM) spontaneously developing PDAC; and (b) to test their diagnostic/predictive value in newly diagnosed PDAC patients and in prediagnostic sera.

Methods and results
The serum reactivity of GEM from inception to invasive cancer, and in resectable or advanced human PDAC was tested by two-dimensional electrophoresis Western blot against proteins from murine and human PDAC cell lines, respectively. A common mouse-to-human autoantibody signature, directed against six antigens identified by MALDI-TOF mass spectrometry, was determined. Of the six antigens, Ezrin displayed the highest frequency of autoantibodies in GEM with early disease and in PDAC patients with resectable disease. The diagnostic value of Ezrin-autoantibodies to discriminate PDAC from controls was further shown by ELISA and ROC analyses (P < 0.0001). This observation was confirmed in prediagnostic sera from the EPIC prospective study in patients who eventually developed PDAC (with a mean time lag of 61.2 months between blood drawing and PDAC diagnosis). A combination of Ezrin-autoantibodies with CA19.9 serum levels and phosphorylated α-Enolase autoantibodies showed an overall diagnostic accuracy of 0.96 ± 0.02.

Conclusions
Autoantibodies against Ezrin are induced early in PDAC and their combination with other serological markers may provide a predictive and diagnostic signature.
The NPR1 ortholog PhaNPR1 is required for the induction of PhaPR1 in Phalaenopsis aphrodite
Authors: Chen Jen-Chih , Lu Hsiang-Chia , Chen Cheng-En , Hsu Hua-Fang , Chen Hong-Hwa , Yeh Hsin-Hung 
Published: September 2013

Abstract

Background
Systematic acquired resistance (SAR) is an effective broad-spectrum defense mechanism that confers long-lasting protection against biotrophic pathogens trough defense related salicylic acid (SA) signaling. Gene(s) involved in SAR have been extensively studied in dicot plants; however, remains largely unresolved in monocot plants. NPR1, an evolutionary conserved gene, plays a central role in SAR, and PR-1 is widely used as a marker for effective SA signaling.

Results
We identified NPR1 and PR-1 homologous genes, PhaNPR1 and PhaPR1, from an economically important orchid, Phalaenopsis aphrodite, and characterized their roles in SA signaling and Cymbidium mosaic virus (CymMV) resistance. A phylogenetic analysis of NPR1 homologs showed that these genes appear to have evolved before angiospermy. Similar to Arabidopsis NPR1, PhaNPR1 was only moderately induced upon SA treatment and CymMV infection. Although PhaPR1 shows only 36% identity with AtPR1, its promoter shared conserved elements with those of other PR-1 genes, and it was induced upon SA treatment and CymMV infection. After CymMV infection, silencing on PhaNPR1 also reduced PhaPR1 expression; however, CymMV accumulation was not affected.

Conclusions
In conclusion, after virus infection, PhaNPR1 is required for PhaPR1 induction, but plays little role in defense against CymMV.
Would you want to know? Public attitudes on early diagnostic testing for Alzheimer's disease
Authors: Wikler Elizabeth M , Blendon Robert J , Benson John M 
Published: September 2013

Abstract
Introduction
Research is underway to develop an early medical test for Alzheimer's disease (AD).

Methods
To evaluate potential demand for such a test, we conducted a cross-sectional telephone survey of 2,678 randomly selected adults across the United States and four European countries.

Results
Most surveyed adults (67%) reported that they are "somewhat" or "very likely" to get an early medical test if one becomes available in the future. Interest was higher among those worried about developing AD, those with an immediate blood relative with AD, and those who have served as caregivers for AD patients. Older respondents and those living in Spain and Poland also exhibited greater interest in testing. Knowing AD is a fatal condition did not influence demand for testing, except among those with an immediate blood relative with the disease.

Conclusions
Potential demand for early medical testing for AD could be high. A predictive test could not only advance medical research, it could transform political and legal landscapes by creating a large constituency of asymptomatic, diagnosed adults.
Moho depth and sediment thickness estimation beneath the Red Sea derived from satellite and terrestrial gravity data
Authors: Salem Ahmed , Green Chris , Campbell Simon , Fairhead J. Derek , Cascone Lorenzo , Moorhead Lee 
Published: September 2013

We sought to map the depth and density contrast of the Mohorovičić discontinuity (Moho) across the Red Sea area and to model sedimentary thickness from gravity data. The gravity data that are used are a combination of satellite and terrestrial gravity data processed into a Bouguer anomaly grid. A 200-km low-pass filter was used to separate this grid into regional and residual gravity grids. We inverted the regional gravity grid to a Moho depth map based on a density contrast map that is constrained by published seismic results. The interpreted Moho is shallowest ([Formula: see text]) along the axis of the central Red Sea, [Formula: see text] along the axis to the south, and [Formula: see text] in the northern Red Sea. The depth increased to [Formula: see text] at the coast and 35–40 km in the adjacent continents. The residual gravity data provided insights into the tectonic fabric along the whole rift and provided a good correlation with magnetic lineaments where these are available. We used the complete Bouguer anomaly to model sedimentary thicknesses constrained by wells and the interpreted Moho. The modeling results are consistent with the presence of large-scale, ridge parallel tilted fault blocks forming subbasins with a maximum depth of about 6–7 km. Our models suggest that the northern Red Sea has an asymmetric basement surface with the western side deeper than the eastern side. The results indicate the presence of oceanic crust in the central and southern parts of the Red Sea, but not in the north. The very thin crust and interpreted oceanic crustal density in the central Red Sea suggest that this area is fully oceanic—although possibly quite young.