bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation
Authors: Davis Richard C , Marsden Ian T , Maloney Michael T , Minamide Laurie S , Podlisny Marcia , Selkoe Dennis J , Bamburg James R 
Published: January 2011

Abstract

Background
Previously we reported 1 μM synthetic human amyloid beta1-42 oligomers induced cofilin dephosphorylation (activation) and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus.

Results
Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t) induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ1-42, the latter lacking tyrosine, acquires a marked increase (620 fold for EC50) in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state), lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ1-42 dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation.

Conclusions
Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory.
Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples
Authors: Nacu Serban , Yuan Wenlin , Kan Zhengyan , Bhatt Deepali , Rivers Celina Sanchez , Stinson Jeremy , Peters Brock A , Modrusan Zora , Jung Kenneth , Seshagiri Somasekar , Wu Thomas D 
Published: January 2011

Abstract

Background
Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome.

Methods
We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays.

Results
Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%.
We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines.

Conclusions
Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as MSMB-NCOA4, may play functional roles in cancer.
COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB)
Authors: Krawczyk-Rusiecka Kinga , Wojciechowska-Durczyńska Katarzyna , Cyniak-Magierska Anna , Adamczewski Zbigniew , Gałecka Elżbieta , Lewiński Andrzej 
Published: January 2011

Abstract

Background
COX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased COX-2 gene expression is believed to participate in carcinogenesis. Recent studies have shown that COX-2 up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. COX-2 products stimulate endothelial cell proliferation and their overexpression has been demonstrated to be involved in the mechanism of decreased resistance to apoptosis. Suppressed angiogenesis was found in experimental animal studies as a consequence of null mutation of COX-2 gene in mice. Despite the role of COX-2 expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear.

Methods
Twenty three (23) patients with cytological diagnosis of PTC were evaluated. After FNAB examination, the needle was washed out with a lysis buffer and the obtained material was used for COX-2 expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. β-actin was used as endogenous control. Relative COX-2 expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ΔΔCT method.

Results

COX-2 gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG).

Conclusions
The preliminary results may indicate COX-2 role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis.
The function and mechanism of COX-2 in angiogenesis of gastric cancer cells
Authors: Yao Liping , Liu Fei , Hong Liu , Sun Li , Liang Shuhui , Wu Kaichun , Fan Daiming 
Published: January 2011

Abstract

Background
Here we aimed to investigate the effect of COX-2 siRNA on proliferation and angiogenesis of gastric cancer cells.

Methods
The gastric cancer cell line SGC7901 was transfected with COX-2 siRNA, then the growth and angiogenesis of cells were detected by in vitro and in vivo assay. Human microarray, RT-PCR and western blot were used to identify differentially expressed angiogenesis-related molecules in cells with decreased expression of COX-2.

Results
Down-regulation of COX-2 could significantly inhibit the in vitro and in vivo growth of gastric cancer cells, and suppress the migration and tube formation of human umbilical vein endothelial cells. Totally 23 angiogenesis-related molecules were found involved in COX-2-induced angiogenesis suppression. The results of RT-PCR and western blot showed that down-regulation of COX-2 might inhibit VEGF, Flt-1, Flk-1/KDR, angiopoietin-1, tie-2, MMP2 and OPN.

Conclusions
COX-2 might mediate tumor angiogenesis and growth, and could be considered as a target for gastric cancer therapy.
Effectiveness of trigger point dry needling for plantar heel pain: study protocol for a randomised controlled trial
Authors: Cotchett Matthew P , Landorf Karl B , Munteanu Shannon E , Raspovic Anita 
Published: January 2011

AbstractBackgroundPlantar heel pain (plantar fasciitis) is a common and disabling condition, which has a detrimental impact on health‐related quality of life. Despite the high prevalence of plantar heel pain, the optimal treatment for this disorder remains unclear. Consequently, an alternative therapy such as dry needling is increasingly being used as an adjunctive treatment by health practitioners. Only two trials have investigated the effectiveness of dry needling for plantar heel pain, however both trials were of a low methodological quality. This manuscript describes the design of a randomised controlled trial to evaluate the effectiveness of dry needling for plantar heel pain.MethodsEighty community‐dwelling men and woman aged over 18 years with plantar heel pain (who satisfy the inclusion and exclusion criteria) will be recruited. Eligible participants with plantar heel pain will be randomised to receive either one of two interventions, (i) real dry needling or (ii) sham dry needling. The protocol (including needling details and treatment regimen) was formulated by general consensus (using the Delphi research method) using 30 experts worldwide that commonly use dry needling for plantar heel pain. Primary outcome measures will be the pain subscale of the Foot Health Status Questionnaire and “first step” pain as measured on a visual analogue scale. The secondary outcome measures will be health related quality of life (assessed using the Short Form‐36 questionnaire ‐ Version Two) and depression, anxiety and stress (assessed using the Depression, Anxiety and Stress Scale ‐ short version). Primary outcome measures will be performed at baseline, 2, 4, 6 and 12 weeks and secondary outcome measures will be performed at baseline, 6 and 12 weeks. Data will be analysed using the intention to treat principle.ConclusionThis study is the first randomised controlled trial to evaluate the effectiveness of dry needling for plantar heel pain. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials and the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines. The findings from this trial will provide evidence for the effectiveness of trigger point dry needling for plantar heel pain.Trial registrationAustralian New Zealand ‘Clinical Trials Registry’. ACTRN12610000611022.
Nutrition outcomes of HIV‐infected malnourished adults treated with ready‐to‐use therapeutic food in sub‐Saharan Africa: a longitudinal study
Authors: Ahoua Laurence , Umutoni Chantal , Huerga Helena , Minetti Andrea , Szumilin Elisabeth , Balkan Suna , Olson David M , Nicholas Sarala , Pujades‐Rodríguez Mar 
Published: January 2011

BackgroundAmong people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub‐Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV‐positive malnourished adults treated with ready‐to‐use therapeutic food and to identify factors associated with nutrition programme failure.MethodsWe present results from a retrospective cohort analysis of patients aged 15 years or older with a body mass index of less than 17 kg/m2 enrolled in three HIV/AIDS care programmes in Africa between March 2006 and August 2008. Factors associated with nutrition programme failure (patients discharged uncured after six or more months of nutritional care, defaulting from nutritional care, remaining in nutritional care for six or more months, or dead) were investigated using multiple logistic regression.ResultsOverall, 1340 of 8685 (15.4%) HIV‐positive adults were enrolled in the nutrition programme. At admission, median body mass index was 15.8 kg/m2 (IQR 14.9‐16.4) and 12% received combination antiretroviral therapy (ART). After a median of four months of follow up (IQR 2.2‐6.1), 524 of 1106 (47.4%) patients were considered cured. An overall total of 531 of 1106 (48.0%) patients failed nutrition therapy, 132 (11.9%) of whom died and 250 (22.6%) defaulted from care. Men (OR = 1.5, 95% CI 1.2‐2.0), patients with severe malnutrition at nutrition programme enrolment (OR = 2.2, 95% CI 1.7‐2.8), and those never started on ART (OR = 4.5, 95% CI 2.7‐7.7 for those eligible; OR = 1.6, 95% CI 1.0‐2.5 for those ineligible for ART at enrolment) were at increased risk of nutrition programme failure. Diagnosed tuberculosis at nutrition programme admission or during follow up, and presence of diarrhoeal disease or extensive candidiasis at admission, were unrelated to nutrition programme failure.ConclusionsConcomitant administration of ART and ready‐to‐use therapeutic food increases the chances of nutritional recovery in these high‐risk patients. While adequate nutrition is necessary to treat malnourished HIV patients, development of improved strategies for the management of severely malnourished patients with HIV/AIDS are urgently needed.
New insights into HIV‐1‐primary skin disorders
Authors: Cedeno‐Laurent Filiberto , Gómez‐Flores Minerva , Mendez Nora , Ancer‐Rodríguez Jesús , Bryant Joseph L , Gaspari Anthony A , Trujillo Jose R 
Published: January 2011

Since the first reports of AIDS, skin involvement has become a burdensome stigma for seropositive patients and a challenging task for dermatologist and infectious disease specialists due to the severe and recalcitrant nature of the conditions. Dermatologic manifestations in AIDS patients act as markers of disease progression, a fact that enhances the importance of understanding their pathogenesis.Broadly, cutaneous disorders associated with HIV type‐1 infection can be classified as primary and secondary. While the pathogenesis of secondary complications, such as opportunistic infections and skin tumours, is directly correlated with a decline in the CD4+ T cell count, the origin of the certain manifestations primarily associated with the retroviral infection itself still remains under investigation.The focus of this review is to highlight the immunological phenomena that occur in the skin of HIV‐1‐seropositive patients, which ultimately lead to skin disorders, such as seborrhoeic dermatitis, atopic dermatitis, psoriasis and eosinophilic folliculitis. Furthermore, we compile the latest data on how shifts in the cytokines milieu, impairments of the innate immune compartment, reactions to xenobiotics and autoimmunity are causative agents in HIV‐1‐driven skin diseases. Additionally, we provide a thorough analysis of the small animal models currently used to study HIV‐1‐associated skin complications, centering on transgenic rodent models, which unfortunately, have not been able to fully unveil the role of HIV‐1 genes in the pathogenesis of their primarily associated dermatological manifestations.
Muscle atrophy induced by SOD1G93A expression does not involve the activation of caspase in the absence of denervation
Authors: Dobrowolny Gabriella , Aucello Michela , Musarò Antonio 
Published: January 2011

Abstract

Background
The most remarkable feature of skeletal muscle is the capacity to adapt its morphological, biochemical and molecular properties in response to several factors. Nonetheless, under pathological conditions, skeletal muscle loses its adaptability, leading to atrophy or wasting. Several signals might function as physiopathological triggers of muscle atrophy. However, the specific mechanisms underlying the atrophic phenotype under different pathological conditions remain to be fully elucidated. In this paper, we address the involvement of caspases in the induction of muscle atrophy in experimental models of amyotrophic lateral sclerosis (ALS) expressing the mutant SOD1G93A transgene either locally or ubiquitously.

Results
We demonstrate that SOD1G93A-mediated muscle atrophy is independent from caspase activity. In particular, the expression of SOD1G93A promotes a reduction of the phosphatidylinositol 3-kinase/Akt pathway associated with activation of forkhead box O3. In contrast, the activation of caspases occurs later and is causally linked to motor neuron degeneration, which is associated with exacerbation of the atrophic phenotype and a shift in fiber-type composition.

Conclusion
This study suggests that muscle atrophy induced by the toxic effect of SOD1G93A is independent from the activation of apoptotic markers and that caspase-mediated apoptosis is a process activated upon muscle denervation.
mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis
Authors: McCann Matthew R , Monemdjou Roxana , Ghassemi-Kakroodi Parisa , Fahmi Hassan , Perez Gemma , Liu Shangxi , Shi-wen Xu , Parapuram Sunil K , Kojima Fumiaki , Denton Christopher P , Abraham David J , Martel-Pelletier Johanne , Crofford Leslie J , Leask Andrew , Kapoor Mohit 
Published: January 2011

Abstract
Introduction
Microsomal prostaglandin E2 synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase (COX) to specifically catalyze the conversion of prostaglandin (PG) H2 to PGE2. mPGES-1 plays a key role in inflammation, pain and arthritis; however, the role of mPGES-1 in fibrogenesis is largely unknown. Herein, we examine the role of mPGES-1 in a mouse model of skin scleroderma using mice deficient in mPGES-1.

Methods
Wild type (WT) and mPGES-1 null mice were subjected to the bleomycin model of cutaneous skin scleroderma. mPGES-1 expressions in scleroderma fibroblasts and in fibroblasts derived from bleomycin-exposed mice were assessed by Western blot analysis. Degree of fibrosis, dermal thickness, inflammation, collagen content and the number of α-smooth muscle actin (α-SMA)-positive cells were determined by histological analyses. The quantity of the collagen-specific amino acid hydroxyproline was also measured.

Results
Compared to normal skin fibroblasts, mPGES-1 protein expression was elevated in systemic sclerosis (SSc) fibroblasts and in bleomycin-exposed mice. Compared to WT mice, mPGES-1-null mice were resistant to bleomycin-induced inflammation, cutaneous thickening, collagen production and myofibroblast formation.

Conclusions
mPGES-1 expression is required for bleomycin-induced skin fibrogenesis. Inhibition of mPGES-1 may be a viable method to alleviate the development of cutaneous sclerosis and is a potential therapeutic target to control the onset of fibrogenesis.
Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury
Authors: Ramakers Bart P , Riksen Niels P , van den Broek Petra , Franke Barbara , Peters Wilbert HM , van der Hoeven Johannes G , Smits Paul , Pickkers Peter 
Published: January 2011

Abstract
Introduction
Preclinical studies have shown that the endogenous nucleoside adenosine prevents excessive tissue injury during systemic inflammation. We aimed to study whether endogenous adenosine also limits tissue injury in a human in vivo model of systemic inflammation. In addition, we studied whether subjects with the common 34C > T nonsense variant (rs17602729) of adenosine monophosphate deaminase (AMPD1), which predicts increased adenosine formation, have less inflammation-induced injury.

Methods
In a randomized double-blinded design, healthy male volunteers received 2 ng/kg E. Coli LPS intravenously with (n = 10) or without (n = 10) pretreatment with the adenosine receptor antagonist caffeine (4 mg/kg body weight). In addition, lipopolysaccharide (LPS) was administered to 10 subjects heterozygous for the AMPD1 34C > T variant.

Results
The increase in adenosine levels tended to be more pronounced in the subjects heterozygous for the AMPD1 34C > T variant (71 ± 22%, P=0.04), compared to placebo- (59 ± 29%, P=0.012) and caffeine-treated (53 ± 47%, P=0.29) subjects, but this difference between groups did not reach statistical significance. Also the LPS-induced increase in circulating cytokines was similar in the LPS-placebo, LPS-caffeine and LPS-AMPD1-groups. Endotoxemia resulted in an increase in circulating plasma markers of endothelial activation [intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)], and in subclinical renal injury, measured by increased urinary excretion of tubular injury markers. The LPS-induced increase of these markers did not differ between the three groups.

Conclusions
Human experimental endotoxemia induces an increase in circulating cytokine levels and subclinical endothelial and renal injury. Although the plasma adenosine concentration is elevated during systemic inflammation, co-administration of caffeine or the presence of the 34C > T variant of AMPD1 does not affect the observed subclinical organ damage, suggesting that adenosine does not affect the inflammatory response and subclinical endothelial and renal injury during human experimental endotoxemia.

Trial Registration
ClinicalTrials (NCT): NCT00513110.
Sleep–wake cycles and cognitive functioning in schizophrenia
Authors: Bromundt Vivien , Köster Matthias , Georgiev-Kill Angela , Opwis Klaus , Wirz-Justice Anna , Stoppe Gabriela , Cajochen Christian 
Published: January 2011

BackgroundIrregular sleep–wake cycles and cognitive impairment are frequently observed in schizophrenia, however, how they interact remains unclear.AimsTo investigate the repercussions of circadian rhythm characteristics on cognitive performance and psychopathology in individuals with schizophrenia.MethodFourteen middle-aged individuals diagnosed with schizophrenia underwent continuous wrist actimetry monitoring in real-life settings for 3 weeks, and collected saliva samples to determine the onset of endogenous melatonin secretion as a circadian phase marker. Moreover, participants underwent multiple neuropsychological testing and clinical assessments throughout the study period.ResultsSleep–wake cycles in individuals with schizophrenia ranged from well entrained to highly disturbed rhythms with fragmented sleep epochs, together with delayed melatonin onsets and higher levels of daytime sleepiness. Participants with a normal rest–activity cycle (objectively determined by high relative amplitude of day/night activity) performed significantly better in frontal lobe function tasks. Stepwise regression analysis revealed that relative amplitude and age represented the best predictors for cognitive performance (Stroop colour–word interference task, Trail Making Test A and B, semantic verbal fluency task), whereas psychopathology (Positive and Negative Syndrome Scale) did not significantly correlate with either cognitive performance levels or the quality of sleep–wake cycles.ConclusionsConsolidated circadian rhythms and sleep may be a prerequisite for adequate cognitive functioning in individuals with schizophrenia.