bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Structure and the Mechanism of Movement of the Gill-Filaments in Teleostei
Authors: Bijtel J. Hubertha 
Published: July 2010

AbstractIt is evident, that the wide apertures between the gills are closed in quiet respiration, during inspiration as well as during expiration, because the filament-tips of the posterior hemibranchia of each gill are in continuous contact with those of the anterior hemibranchia of the next gill. The communication between the inspiratory and the expiratory cavity is kept up by the narrow slits between the lamellae. The skeleton and the ligament apparatus of the filaments are constructed in such a way, that the normal position of abduction of both filament-rows of a gill is maintained in spite of the fact, that in both respiratory phases the pressure in the inspiratory cavity is higher than that in the expiratory cavity. The figures of gills of the Teleostei, which are found in different textbooks, show a wide aperture between the filament-tips of the hemibranchiae of two successive gills. In the living animal this wide communication between the inspiratory and the expiratory cavity does not exist in quiet respiration, but is only seen during the coughing movements. Small fragments of defilement, which are accumulated against the gills, are then removed and are spit out by the mouth (coughing in a forward direction) or appear from under the gill-cover with the respiratory water (coughing in backward direction). During coughing an adduction movement is seen of the filament-tips of the two hemibranchiae of a gill by the contraction of the adductor muscles. The adductor muscles do not act rhythmically. They play no part in the circulation of the blood through the branchial vessels (RIESS 1881, WOSKOBOINIKOFF 1932), nor in the renewal of the respiratory water (ELFRIEDE SCHÖTTLE 1932), but they are of significance for the cleaning of the gills by means of the coughing movements. During coughing the so-called abductor muscles probably prevent a caudal movement of the adducted filament-rows of a gill, by which the branchial apertures could be closed up. It is possible, that they act exclusively during coughing in a forward direction.
Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial
Authors: Dreger Peter , Döhner Hartmut , Ritgen Matthias , Böttcher Sebastian , Busch Raymonde , Dietrich Sascha , Bunjes Donald , Cohen Sandra , Schubert Jörg , Hegenbart Ute , Beelen Dietrich , Zeis Matthias , Stadler Michael , Hasenkamp Justin , Uharek Lutz , Scheid Christof , Humpe Andreas , Zenz Thorsten , Winkler Dirk , Hallek Michael , Kneba Michael , Schmitz Norbert , Stilgenbauer Stephan ,   for the German CLL Study Group
Published: July 2010

Abstract
The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p−). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p−, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.
High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine
Authors: Bachas Costa , Schuurhuis Gerrit Jan , Hollink Iris H. I. M. , Kwidama Zinia J. , Goemans Bianca F. , Zwaan C. Michel , van den Heuvel-Eibrink Marry M. , de Bont Eveline S. J. M. , Reinhardt Dirk , Creutzig Ursula , de Haas Valerie , Assaraf Yehuda G. , Kaspers Gertjan J. L. , Cloos Jacqueline 
Published: July 2010

AbstractAlthough virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific molecular aberrations. To determine relevance of established AML type I/II mutations that may serve as therapeutic targets, we assessed frequencies of these mutations and their persistence during disease progression in a large group (n = 69) of paired diagnosis and relapse pediatric AML specimens. In 26 of 42 patients (61%) harboring mutations at either stage of the disease, mutation status changed between diagnosis and relapse, particularly in FLT3, WT1, and RAS genes. Presence or gain of type I/II mutations at relapse was associated with a shorter time to relapse (TTR), whereas absence or loss correlated with longer TTR. Moreover, an adverse outcome was found for patients with activating mutations at relapse, which was statistically significant for FLT3/ITD and WT1 mutations. These findings suggest that mutational shifts affect disease progression. We hence propose that risk stratification, malignant cell detection, and selection of personalized treatment should be based on status of type I/II mutations both at initial diagnosis and during follow-up.
Identification of baboon microRNAs expressed in liver and lymphocytes
Authors: Karere Genesio M , Glenn Jeremy P , VandeBerg John L , Cox Laura A 
Published: July 2010

Abstract

Background
MicroRNAs (miRNAs) are small noncoding RNAs (~22 nucleotides) that regulate gene expression by cleaving mRNAs or inhibiting translation. The baboon is a well-characterized cardiovascular disease model; however, no baboon miRNAs have been identified. Evidence indicates that the baboon and human genomes are highly conserved; based on this conservation, we hypothesized that comparative genomic methods could be used to identify baboon miRNAs.

Methods
We employed an in silico comparative genomics approach and human miRNA arrays to identify baboon expressed miRNAs in liver (n = 6) and lymphocytes (n = 6). Expression profiles for selected miRNAs in multiple tissues were validated by RT-PCR.

Results
We identified in silico 555 putative baboon pre-miRNAs, of which 41% exhibited 100% identity and an additional 58% shared more than 90% sequence identity with human pre-miRNAs. Some of these miRNAs are primate-specific and are clustered in the baboon genome like human miRNA clusters. We detected expression of 494 miRNAs on the microarray and validated expression of selected miRNAs in baboon liver and lymphocytes by RT-PCR. We also observed miRNA expression in additional tissues relevant to dyslipidemia and atherosclerosis. Approximately half of the miRNAs expressed on the array were not predicted in silico suggesting that we have identified novel baboon miRNAs, which could not be predicted using the current draft of the baboon genome.

Conclusion
We identified a subset of baboon miRNAs using a comparative genomic approach, identified additional baboon miRNAs using a human array and showed tissue-specific expression of baboon miRNAs. Our discovery of baboon miRNAs in liver and lymphocytes will provide resources for studies on the roles of miRNAs in dyslipidemia and atherosclerosis, and for translational studies.
Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels
Authors: Schniedermann Judith , Rennecke Moritz , Buttler Kerstin , Richter Georg , Städtler Anna-Maria , Norgall Susanne , Badar Muhammad , Barleon Bernhard , May Tobias , Wilting Jörg , Weich Herbert A 
Published: July 2010

Abstract

Background
Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated.

Results
In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels.
Mouse lung microvascular endothelial cells (MLMVECs) were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony). These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs) in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels.

Conclusion
The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.
Modeling secondary level of HIV contact tracing: its impact on HIV intervention in Cuba
Authors: Hsieh Ying-Hen , Wang Yun-Shih , de Arazoza Hector , Lounes Rachid 
Published: July 2010

Abstract

Background
Universal HIV testing/treatment program has currently been suggested and debated as a useful strategy for elimination of HIV epidemic in Africa, although not without practical issues regarding the costs and feasibility of a fully implemented program.

Methods
A mathematical model is proposed which considers two levels of detection of HIV-infectives through contact tracing of known infectives in addition to detections through other means such as random screening. Simulations based on Cuban contact tracing data were performed to ascertain the potential impact of the different levels of contact tracing.

Results
Simulation studies illustrate that: (1) contact tracing is an important intervention measure which, while less effective than random screening, is perhaps less costly and hence ideal for large-scale intervention programs in developing countries with less resources; (2) the secondary level of contact tracing could significantly change the basic disease transmission dynamics, depending on the parameter values; (3) the prevalence of the epidemic at the time of implementation of contact tracing program might be a crucial factor in determining whether the measure will be effective in preventing disease infections and its eventual eradication.

Conclusions
Our results indicate that contact tracing for detection of HIV infectives could be suitably used to remedy inadequacies in a universal HIV testing program when designing timely and effective intervention measures.
Modeling the Aneuploidy Control of Cancer
Authors: Li Yao , Berg Arthur , Wu Louie R , Wang Zhong , Chen Gang , Wu Rongling 
Published: July 2010

Abstract

Background
Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer.

Methods
We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm.

Results
Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model.

Conclusions
The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.
The tumor suppressor gene KCTD11
REN
is regulated by Sp1 and methylation and its expression is reduced in tumors
Authors: Mancarelli M Michela , Zazzeroni Francesca , Ciccocioppo Lucia , Capece Daria , Po Agnese , Murgo Simona , Di Camillo Raffaello , Rinaldi Christian , Ferretti Elisabetta , Gulino Alberto , Alesse Edoardo 
Published: July 2010

Abstract
A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11

REN
(KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells.
Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice
Authors: Meissner Maxi , Nijstad Niels , Kuipers Folkert , Tietge Uwe JF 
Published: July 2010

Abstract
Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT). After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day) plasma triglycerides were lower (p < 0.05), while otherwise lipid and lipoprotein levels did not change. Macrophage cholesterol efflux towards plasma was significantly increased in running (n = 8) compared to sedentary (n = 6) mice (14.93 ± 1.40 vs. 12.33 ± 2.60%, p < 0.05). In addition, fecal excretion of bile acids (3.86 ± 0.50 vs. 2.90 ± 0.51 nmol/d, p = 0.001) and neutral sterols (2.75 ± 0.43 vs. 1.94 ± 0.22 nmol/d, p < 0.01) was significantly higher in running mice. However, RCT from macrophages to feces remained essentially unchanged in running mice compared with sedentary controls (bile acids: 3.2 ± 1.0 vs. 2.9 ± 1.1 % of injected dose, n.s.; neutral sterols: 1.4 ± 0.7 vs. 1.1 ± 0.5 % injected dose, n.s.). Judged by the plasma lathosterol to cholesterol ratio, endogenous cholesterol synthesis was increased in exercising mice (0.15 ± 0.03 vs. 0.11 ± 0.02, p < 0.05), while the hepatic mRNA expression of key transporters for biliary cholesterol (Abcg5/g8, Sr-bI) as well as bile acid (Abcb11) and phospholipd (Abcb4) excretion did not change. These data indicate that the beneficial effects of exercise on cardiovascular health include increased cholesterol efflux, but do not extend to other components of RCT. The increased fecal cholesterol excretion observed in running mice is likely explained by higher endogenous cholesterol synthesis, however, it does not reflect increased RCT in the face of unchanged expression of key transporters for biliary sterol secretion.
Changes in Aβ Non-Nociceptive Primary Sensory Neurons in a Rat Model of Osteoarthritis Pain
Authors: Wu Qi , Henry James L 
Published: July 2010

Background: Pain is a major debilitating factor in osteoarthritis (OA), yet few mechanism-based therapies are available. To address the need to understand underlying mechanisms the aim of the present study was to determine changes in sensory neurons in an animal model of OA pain. Results: The model displayed typical osteoarthritis pathology characterized by cartilage degeneration in the knee joint and also manifested knee pathophysiology (edema and increased vasculature permeability of the joint) and altered nociception of the affected limb (hind paw tenderness and knee articulation-evoked reduction in the tail flick latency). Neurons included in this report innervated regions throughout the entire hind limb. Aβ-fiber low threshold mechanoreceptors exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and slower maximum rising rate, and muscle spindle neurons were the most affected subgroup. Only minor AP configuration changes were observed in either C- or Aδ-fiber nociceptors. Conclusion: Thus, at one month after induction of the OA model Aβ-fiber low threshold mechanoreceptors but not C- or Aδ-fiber nociceptors had undergone changes in electrophysiological properties. If these changes reflect a change in functional role of these neurons in primary afferent sensory processing, then Aβ-fiber non-nociceptive primary sensory neurons may be involved in the pathogenesis of OA pain. Further, it is important to point out that the patterns of the changes we observed are consistent with observations in models of peripheral neuropathy but not models of peripheral inflammation.
Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment
Authors: Buhrmann Constanze , Mobasheri Ali , Matis Ulrike , Shakibaei Mehdi 
Published: July 2010

Abstract
Introduction
Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1β activates the transcription factor nuclear factor-κB (NF-κB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation.

Methods
MSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1β.

Results
We demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1β-induced activation of NF-κB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1β stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), β1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2.

Conclusions
Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.
Research Resource: Gonadotropin-Releasing Hormone Receptor-Mediated Signaling Network in LβT2 Cells: A Pathway-Based Web-Accessible Knowledgebase
Authors: Fink Marc Y. , Pincas Hanna , Choi Soon Gang , Nudelman German , Sealfon Stuart C. 
Published: July 2010

AbstractThe GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LβT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators. In order to facilitate access to the information contained in this complex and evolving literature, we have developed a pathway-based knowledgebase that is web hosted. At present, using 106 relevant primary publications, we curated a comprehensive knowledgebase of the GnRHR signaling in the LβT2 cell in the form of a process diagram. Positive and negative controls of gonadotropin gene expression, which included GnRH itself, hypothalamic factors, gonadal steroids and peptides, as well as other hormones, were illustrated. The knowledgebase contains 187 entities and 206 reactions. It was assembled using CellDesigner software, which provides an annotated graphic representation of interactions, stored in Systems Biology Mark-up Language. We then utilized Biological Pathway Publisher, a software suite previously developed in our laboratory, to host the knowledgebase in a web-accessible format as a public resource. In addition, the network entities were linked to a public wiki, providing a forum for discussion, updating, and error correction. The GnRHR-signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html.