bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis
Authors: Wang Chong , Li Yan-Yuan , Li Xiang , Wei Li-Liang , Yang Xiu-Yun , Xu Dan-Dan , Jiang Ting-Ting , Li Zhong-Jie , Chen Zhong-Liang , Zhang Xing , Liu Ji-Yan , Ping Ze-Peng , Li Ji-Cheng 
Published: January 2014

AbstractBackgroundMycobacterium tuberculosisinfection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation.MethodsClinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups.ResultsWe found significantly higher levels of serum C4b and PEPD (P = 0.018,P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05,P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05).ConclusionsOur study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB.
Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells
Authors: Demir Ummuhan , Koehler Andrea , Schneider Rainer , Schweiger Susann , Klocker Helmut 
Published: January 2014

Abstract

Background
Metformin is an approved drug prescribed for diabetes. Its role as an anti-cancer agent has drawn significant attention because of its minimal side effects and low cost. However, its mechanism of anti-tumour action has not yet been fully clarified.

Methods
The effect on cell growth was assessed by cell counting. Western blot was used for analysis of protein levels, Boyden chamber assays for analyses of cell migration and co-immunoprecipitation (CoIP) followed by western blot, PCR or qPCR for analysis of protein-protein and protein-mRNA interactions.

Results
Metformin showed an anti-proliferative effect on a wide range of prostate cancer cells. It disrupted the AR translational MID1 regulator complex leading to release of the associated AR mRNA and subsequently to downregulation of AR protein in AR positive cell lines. Inhibition of AR positive and negative prostate cancer cells by metformin suggests involvement of additional targets. The inhibitory effect of metformin was mimicked by disruption of the MID1-α4/PP2A protein complex by siRNA knockdown of MID1 or α4 whereas AMPK activation was not required.

Conclusions
Findings reported herein uncover a mechanism for the anti-tumor activity of metformin in prostate cancer, which is independent of its anti-diabetic effects. These data provide a rationale for the use of metformin in the treatment of hormone naïve and castration-resistant prostate cancer and suggest AR is an important indirect target of metformin.
ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma
Authors: Eckel-Passow Jeanette E , Serie Daniel J , Bot Brian M , Joseph Richard W , Cheville John C , Parker Alexander S 
Published: January 2014

Abstract

Background
An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC.

Methods
We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between patients with (n = 23) and without (n = 42) a history of smoking. Analyses were first stratified on obesity status (the other primary risk factor for ccRCC) and then combined and analyzed together. To identify genes where the fold change in smokers relative to non-smokers was different in tumor tissues in comparison to patient-matched normal kidney tissues, we identified Affymetrix probesets that had a significant tissue type-by-smoking status interaction pvalue. We then performed RT-PCR validation on the top eight candidate genes in an independent sample of 28 smokers and 54 non-smokers.

Results
We identified 15 probesets that mapped to eight genes that had candidate associations with smoking-related ccRCC: ANKS1B, ACOT6, PPWD1, EYS, LIMCH1, CHRNA6, MT1G, and ZNF600. Using RT-PCR, we validated that expression of ANKS1B is preferentially down-regulated in smoking-related ccRCC.

Conclusion
We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. Thus, ANKS1B should be explored further as a novel avenue for early detection as well as prevention of ccRCC in smokers.
Prognostic analysis of gastric gastrointestinal stromal tumor with synchronous gastric cancer
Authors: Lin Mi , Lin Jian-Xian , Huang Chang-Ming , Zheng Chao-Hui , Li Ping , Xie Jian-Wei , Wang Jia-Bin , Lu Jun 
Published: January 2014

Abstract

Background
Many patients with gastric gastrointestinal stromal tumor (GIST) and synchronous gastric cancer have been described, most in single case studies. We retrospectively investigated the clinicopathologic features and prognostic effects of gastric GIST in patients with synchronous gastric cancer.

Methods
The study enrolled 170 patients with gastric GIST, who had undergone complete surgical resection (R0) from January 2000 to December 2011. Forty-two patients had synchronous gastric cancer (CA Group), whereas 128 did not (Non-CA Group). The clinicopathologic features and potential prognostic factors in the two groups were compared.

Results
Patients in the CA Group had more obvious symptoms, but a lower rate of preoperative diagnosis of gastric GIST (P <0.05). The two groups differed significantly in gender, age, greatest tumor diameter, risk stratification, tumor-associated ulcers, and CD117 and CD34 expression (P <0.05 each). Univariate analysis showed that age, risk stratification, postoperative oral imatinib and synchronous gastric cancer were predictive factors of survival (P <0.05). Cox regression analysis showed that risk stratification, postoperative oral imatinib and synchronous gastric cancer were independent predictors of survival (P <0.05). Stratified analysis showed that the 5-year overall survival rate was lower in patients with synchronous gastric cancer than in those without synchronous gastric cancer.

Conclusions
Gastric GIST with synchronous gastric cancer had a lower rate of preoperative diagnosis, with correct diagnosis often missed. Survival, however, depended primarily on the gastric cancer.
Ethnomedicine use in the war affected region of northwest Pakistan
Authors: Adnan Muhammad , Ullah Ihsan , Tariq Akash , Murad Waheed , Azizullah Azizullah , Khan Abdul Latif , Ali Nawab 
Published: January 2014

Abstract
Background
North-West of Pakistan is bestowed with medicinal plant resources due to diverse geographical and habitat conditions. The traditional use of plants for curing various diseases forms an important part of the region’s cultural heritage. The study was carried out to document medicinal plants used in Frontier Region (FR) Bannu, an area affected by the “War on Terror”.

Methods
Fieldwork was carried out in four different seasons (spring, autumn, summer and winter) from March 2012 to February 2013. Data on medicinal plants was collected using structured and semi-structured questionnaires from 250 respondents. The voucher specimens were collected, processed and identified following standard methods.

Results
Of the 107 species of ethnomedicinal plants reported, fifty percent species are herbaceous. The majority of the reported species were wild (55%) but a substantial proportion are cultivated (29%). For most of the plant species (34%), leaves are the most commonly used part in the preparation of ethnomedicines. The most common use of species is for carminative purposes (14 species), with the next most common use being for blood purification (11 species). The main methods used in the preparation of ethnomedicinal recipes involves grinding and boiling, and nearly all the remedies are taken orally along with ingredients such as water, milk or honey for ease of ingestion. Traditional healers prepare plant remedies using one or more plants. There was a significant correlation (r2 = 0.95) between the age of local people and the number of plants known to them, which indicates that in the coming 20 years, an approximate decrease of 75% in the indigenous knowledge may be expected.

Conclusion
Traditional medicines are important to the livelihoods of rural communities in the region affected by the Global war on Terrorism. The medicinal recipes are indigenous; however, there is a threat to their future use on account of rapid modernization and terrorist activities. Documentation of medicinal plants and recipes may help in the conservation of the regional indigenous medicinal knowledge for future generations and to provide a baseline for further studies.
Reduction of meckelin leads to general loss of cilia, ciliary microtubule misalignment and distorted cell surface organization
Authors: Picariello Tyler , Valentine Megan Smith , Yano Junji , Van Houten Judith 
Published: January 2014

Abstract

Background
Meckelin (MKS3), a conserved protein linked to Meckel Syndrome, assists in themigration of centrioles to the cell surface for ciliogenesis. We explored foradditional functions of MKS3p using RNA interference (RNAi) and expression of FLAGepitope tagged protein in the ciliated protozoan Paramecium tetraurelia.This cell has a highly organized cell surface with thousands of cilia and basalbodies that are grouped into one or two basal body units delineated by ridges. Thehighly systematized nature of the P. tetraurelia cell surface provides aresearch model of MKS and other ciliopathies where changes in ciliary structure,subcellular organization and overall arrangement of the cell surface can be easilyobserved. We used cells reduced in IFT88 for comparison, as theinvolvement of this gene’s product with cilia maintenance and growth is wellunderstood.

Results
FLAG-MKS3p was found above the plane of the distal basal body in the transitionzone. Approximately 95% of those basal bodies observed had staining for FLAG-MKS3.The RNAi phenotype for MKS3 depleted cells included global shortening andloss of cilia. Basal body structure appeared unaffected. On the dorsal surface,the basal bodies and their associated rootlets appeared rotated out of alignmentfrom the normal anterior-posterior rows. Likewise, cortical units were abnormal inshape and out of alignment from normal rows. A GST pull down using the MKS3coiled-coil domain suggests previously unidentified interacting partners.

Conclusions
Reduction of MKS3p shows that this protein affects development and maintenance ofcilia over the entire cell surface. Reduction of MKS3p is most visible on thedorsal surface. The anterior basal body is attached to and moves along thestriated rootlet of the posterior basal body in preparation for duplication. Wepropose that with reduced MKS3p, this attachment and guidance of the basal body islost. The basal body veers off course, causing basal body rows to be misalignedand units to be misshapen. Rootlets form normally on these misaligned basal bodiesbut are rotated out of their correct orientation. Our hypothesis is furthersupported by the identification of novel interacting partners of MKS3p including akinetodesmal fiber protein, KdB2.
Labor market policies and IMF advice in advanced economies during the Great Recession
Authors: Blanchard Olivier J , Jaumotte Florence , Loungani Prakash 
Published: January 2014

Abstract
In this paper we present and analyze the IMF’s labor market recommendations for advanced economies since the beginning of the crisis, both in general and specifically in program countries. Our analysis is informed by our reading of the theoretical and empirical literature on the design of labor market policies and institutions in advanced economies. We organize our discussion around two concepts: micro flexibility, namely the ability of the economy to allow for the reallocation of workers to jobs needed to sustain growth; and macro flexibility, namely the ability of the economy to adjust to macroeconomic shocks. Achieving both types of flexibility while protecting workers and maintaining incentives for workers and firms to invest in existing relations, is not that simple, and the design of labor market institutions faces delicate trade-offs.

JEL codes

E2, J3, J5, J6
Low-density lipoprotein receptor–related protein 5 governs Wnt-mediated osteoarthritic cartilage destruction
Authors: Shin Youngnim , Huh Yun Hyun , Kim Kieun , Kim Suyeon , Park Ka Hyon , Koh Jeong-Tae , Chun Jang-Soo , Ryu Je-Hwang 
Published: January 2014

Abstract
Introduction
Wnt ligands bind to low-density lipoprotein receptor–related protein (LRP) 5 or 6, triggering a cascade of downstream events that include β-catenin signaling. Here we explored the roles of LRP5 in interleukin 1β (IL-1β)- or Wnt-mediated osteoarthritic (OA) cartilage destruction in mice.

Methods
The expression levels of LRP5, type II collagen, and catabolic factors were determined in mouse articular chondrocytes, human OA cartilage, and mouse experimental OA cartilage. Experimental OA in wild-type, Lrp5 total knockout (Lrp5-/-) and chondrocyte-specific knockout (Lrp5
fl/fl
;Col2a1-cre) mice was caused by aging, destabilization of the medial meniscus (DMM), or intra-articular injection of collagenase. The role of LRP5 was confirmed in vitro by small interfering RNA–mediated knockdown of Lrp5 or in Lrp5-/- cells treated with IL-1β or Wnt proteins.

Results
IL-1β treatment increased the expression of LRP5 (but not LRP6) via JNK and NF-κB signaling. LRP5 was upregulated in human and mouse OA cartilage, and Lrp5 deficiency in mice inhibited cartilage destruction. Treatment with IL-1β or Wnt decreased the level of Col2a1 and increased those of Mmp3 or Mmp13, whereas Lrp5 knockdown ameliorated these effects. In addition, we found that the functions of LRP5 in arthritic cartilage were subject to transcriptional activation by β-catenin. Moreover, Lrp5-/- and Lrp5
fl/fl
;Col2a1-cre mice exhibited decreased cartilage destruction (and related changes in gene expression) in response to experimental OA.

Conclusions
Our findings indicate that LRP5 (but not LRP6) plays an essential role in Wnt/β-catenin-signaling-mediated OA cartilage destruction in part by regulating the expression levels of type II collagen, MMP3, and MMP13.
The effect of pressure on rock properties in the Gulf of Mexico: Comparison between compaction disequilibrium and unloading
Authors: Yu Hua , Hilterman Fred J. 
Published: January 2014

We used statistical methods on rock properties derived from more than 480 wells to catalog shale velocity and density trends in different pressure regimes in the Gulf of Mexico and evaluated the reasons for their variations. A detailed evaluation of the density and velocity trends revealed that in the northern part of the Louisiana shelf, unloading is the major mechanism of overpressure. The onset of overpressure occurs at depths around 3000 m where temperatures are normally greater than 70°C. The relationship of the temperature gradient increase and the velocity decrease to the smectite-illite transformation allowed us to believe that inelastic unloading may be the major mechanism for overpressure in this region. On the other hand, in the southern part of the Louisiana shelf, abnormal pore pressure is often caused by compaction disequilibrium where the sediment section has a low sand percentage. In this type of pressure regime, velocity and density values cease to change at the onset of overpressure and essentially remain at the same value below the onset.
Non-fatal repetition of self-harm in Taipei City, Taiwan: cohort study
Authors: Kwok Chi-Leung , Yip Paul S. F. , Gunnell David , Kuo Chian-Jue , Chen Ying-Yeh 
Published: January 2014

BackgroundRepeat self-harm is an important risk factor for suicide. Few studies have explored risk factors for non-fatal repeat self-harm in Asia.AimsTo investigate the risk of non-fatal repeat self-harm in a large cohort of patients presenting to hospital in Taipei City, Taiwan.MethodProspective cohort study of 7601 patients with self-harm presenting to emergency departments (January 2004–December 2006). Survival analysis was used to examine the rates, timing and factors associated with repeat self-harm.ResultsIn total 778 (10.2%) patients presented to hospital with one or more further episodes of self-harm. The cumulative risk of non-fatal repetition within 1 year of a self-harm episode was 9.3% (95% CI 8.7–10.1). The median time to repetition within 1 year was 105 days. Females had a higher incidence of repeat self-harm than males (adjusted hazard ratio 1.25, 95% CI 1.05–1.48) but males had shorter median time to repetition (107v.80 days). Other independent risk factors for repeat self-harm within 1 year of an index episode were: young age, self-harm by medicine overdose and increasing number of repeat episodes of self-harm.ConclusionsThe risk of non-fatal repeat self-harm in Taipei City is lower than that seen in the West. Risk factors for repeat non-fatal self-harm differ from those for fatal self-harm. The first 3 months after self-harm is a crucial period for intervention.
Cellular characterization of ultrasound-stimulated microbubble radiation enhancement
Authors: Al-Mahrouki Azza A. , Iradji Sara , Tran William Tyler , Czarnota Gregory J. 
Published: January 2014

Abstract
Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in prostate cancer xenografts. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment which consisted of radiation treatments alone (2 Gy or 8 Gy), or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) revealed increased cell death, within tumors exposed to combined treatments compared to untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67), blood leakage (factor VIII), angiogenesis (Cluster of differentiation molecule, CD31), ceramide-formation, angiogenesis signaling (vascular endothelial growth factor, VEGF), oxygen limitation (prolyl hydroxylases, PHD2), and DNA damage/repair (gamma H2AX). Results demonstrated, reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production, and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach may be a feasible option as a novel enhancing approach in radiation therapy.
Mosaic analysis and tumor induction in zebrafish by microsatellite instability-mediated stochastic gene expression
Authors: Koole Wouter , Tijsterman Marcel 
Published: January 2014

Abstract
Mosaic analysis, in which two or more populations of cells with differing genotypes are studied in a single animal, is a powerful approach to study developmental mechanisms and gene function in vivo. Over recent years several genetic methods have been developed to achieve mosaicism in zebrafish, but despite their advances, limitations remain and different approaches and further refinements are warranted. Here, we describe an alternative approach to create somatic mosaicism in zebrafish that relies on the instability of microsatellite sequences during replication. We placed the coding sequences of various marker proteins behind a microsatellite and out-of-frame; in vivo frameshifting into the proper reading frame results in expression of the protein in random individual cells that are surrounded by wildtype cells. We optimized this approach for the binary Gal4-UAS expression system by generating a driver line and effector lines that stochastically express Gal4-VP16 or UAS:H2A-EGFP and self-maintaining UAS:H2A-EGFP-Kaloop, respectively. To demonstrate the utility of this system we stochastically expressed a constitutively active form of the human oncogene H-RAS and show the occurrence of hyperpigmentation and sporadic tumors within 5 days. Our data demonstrate that inducing somatic mosaicism via microsatellite instability can be a valuable approach for mosaic analysis and tumor induction in Danio rerio.
Regulation of Src trafficking and activation by the endocytic regulatory proteins MICAL-L1 and EHD1
Authors: Reinecke James B. , Katafiasz Dawn , Naslavsky Naava , Caplan Steve 
Published: January 2014

ABSTRACT
Localization of the non-receptor tyrosine kinase Src to the cell periphery is required for its activation and to mediate focal adhesion turnover, cell spreading and migration. Inactive Src localizes to a perinuclear compartment and the movement of Src to the plasma membrane is mediated by endocytic transport. However, the precise pathways and regulatory proteins that are responsible for SRC transport are incompletely understood. Here, we demonstrate that Src partially colocalizes with the endocytic regulatory protein MICAL-L1 (molecule interacting with CasL-like protein 1) in mammalian cells. Furthermore, MICAL-L1 is required for growth-factor- and integrin-induced Src activation and transport to the cell periphery in HeLa cells and human fibroblasts. Accordingly, MICAL-L1 depletion impairs focal adhesion turnover, cell spreading and cell migration. Interestingly, we find that the MICAL-L1 interaction partner EHD1 (EH domain-containing protein 1) is also required for Src activation and transport. Moreover, the MICAL-L1-mediated recruitment of EHD1 to Src-containing recycling endosomes is required for the release of Src from the perinuclear endocytic recycling compartment in response to growth factor stimulation. Our study sheds new light on the mechanism by which Src is transported to the plasma membrane and activated, and provides a new function for MICAL-L1 and EHD1 in the regulation of intracellular non-receptor tyrosine kinases.