bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states
Authors: Pham Thu-Hang , Benner Christopher , Lichtinger Monika , Schwarzfischer Lucia , Hu Yuhui , Andreesen Reinhard , Chen Wei , Rehli Michael 
Published: May 2012

AbstractCellular differentiation is orchestrated by lineage-specific transcription factors and associated with cell type–specific epigenetic signatures. In the present study, we used stage-specific, epigenetic “fingerprints” to deduce key transcriptional regulators of the human monocytic differentiation process. We globally mapped the distribution of epigenetic enhancer marks (histone H3 lysine 4 monomethylation, histone H3 lysine 27 acetylation, and the histone variant H2AZ), describe general properties of marked regions, and show that cell type–specific epigenetic “fingerprints” are correlated with specific, de novo–derived motif signatures at all of the differentiation stages studied (ie, hematopoietic stem cells, monocytes, and macrophages). We validated the novel, de novo–derived, macrophage-specific enhancer signature, which included ETS, CEBP, bZIP, EGR, E-Box and NF-κB motifs, by ChIP sequencing for a subset of motif corresponding transcription factors (PU.1, C/EBPβ, and EGR2), confirming their association with differentiation-associated epigenetic changes. We describe herein the dynamic enhancer landscape of human macrophage differentiation, highlight the power of genome-wide epigenetic profiling studies to reveal novel functional insights, and provide a unique resource for macrophage biologists.
Identification of early gene expression changes during human Th17 cell differentiation
Authors: Tuomela Soile , Salo Verna , Tripathi Subhash K. , Chen Zhi , Laurila Kirsti , Gupta Bhawna , Äijö Tarmo , Oikari Lotta , Stockinger Brigitta , Lähdesmäki Harri , Lahesmaa Riitta 
Published: April 2012

AbstractTh17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation through genome-wide gene expression profiling. CD4+ cells isolated from umbilical cord blood were used to determine detailed kinetics of gene expression after initiation of Th17 differentiation with IL1β, IL6, and TGFβ. The differential expression of selected candidate genes was further validated at protein level and analyzed for specificity in initiation of Th17 compared with initiation of other Th subsets, namely Th1, Th2, and iTreg. This first genome-wide profiling of transcriptomics during the induction of human Th17 differentiation provides a starting point for defining gene regulatory networks and identifying new candidates regulating Th17 differentiation in humans.
Beyond Hox: the role of ParaHox genes in normal and malignant hematopoiesis
Authors: Rawat Vijay P. S. , Humphries R. Keith , Buske Christian 
Published: May 2012

AbstractDuring the past decade it was recognized that homeobox gene families such as the clustered Hox genes play pivotal roles both in normal and malignant hematopoiesis. More recently, similar roles have also become apparent for members of the ParaHox gene cluster, evolutionarily closely related to the Hox gene cluster. This is in particular found for the caudal-type homeobox genes (Cdx) genes, known to act as upstream regulators of Hox genes. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. Correlative studies indicate that CDX2 functions as master regulator of perturbed HOX gene expression in human acute myeloid leukemia, locating this ParaHox gene at a central position for initiating and maintaining HOX gene dysregulation as a driving leukemogenic force. There are still few data about potential upstream regulators initiating aberrant CDX2 expression in human leukemias or about critical downstream targets of CDX2 in leukemic cells. Characterizing this network will hopefully open the way to therapeutic approaches that target deregulated ParaHox genes in human leukemia.
Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party
Authors: Marsh Judith C. , Bacigalupo Andrea , Schrezenmeier Hubert , Tichelli Andre , Risitano Antonio M. , Passweg Jakob R. , Killick Sally B. , Warren Alan J. , Foukaneli Theodora , Aljurf Mahmoud , Al-Zahrani H. A. , Schafhausen Philip , Roth Alexander , Franzke Anke , Brummendorf Tim H. , Dufour Carlo , Oneto Rosi , Sedgwick Philip , Barrois Alain , Kordasti Shahram , Elebute Modupe O. , Mufti Ghulam J. , Socie Gerard 
Published: April 2012

Abstract
Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity–matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.
Platelets can enhance vascular permeability
Authors: Cloutier Nathalie , Paré Alexandre , Farndale Richard W. , Schumacher H. Ralph , Nigrovic Peter A. , Lacroix Steve , Boilard Eric 
Published: April 2012

AbstractPlatelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.
Rapid development of exhaustion and down-regulation of eomesodermin limit the antitumor activity of adoptively transferred murine natural killer cells
Authors: Gill Saar , Vasey Adrianne E. , De Souza Alysha , Baker Jeanette , Smith Aaron T. , Kohrt Holbrook E. , Florek Mareike , Gibbs Kenneth D. , Tate Keri , Ritchie David S. , Negrin Robert S. 
Published: April 2012

Abstract
Natural killer (NK) cells are potent anti-viral and antitumor “first responders” endowed with natural cytotoxicity and cytokine production capabilities. To date, attempts to translate these promising biologic functions through the adoptive transfer of NK cells for the treatment of cancer have been of limited benefit. Here we trace the fate of adoptively transferred murine NK cells and make the surprising observation that NK cells traffic to tumor sites yet fail to control tumor growth or improve survival. This dysfunction is related to a rapid down-regulation of activating receptor expression and loss of important effector functions. Loss of interferon (IFN)γ production occurs early after transfer, whereas loss of cytotoxicity progresses with homeostatic proliferation and tumor exposure. The dysfunctional phenotype is accompanied by down-regulation of the transcription factors Eomesodermin and T-bet, and can be partially reversed by the forced overexpression of Eomesodermin. These results provide the first demonstration of NK-cell exhaustion and suggest that the NK-cell first-response capability is intrinsically limited. Further, novel approaches may be required to circumvent the described dysfunctional phenotype.
The hemodynamic tolerability and feasibility of sustained low efficiency dialysis in the management of critically ill patients with acute kidney injury
Authors: Fieghen Heather E , Friedrich Jan O , Burns Karen E , Nisenbaum Rosane , Adhikari Neill K , Hladunewich Michelle A , Lapinsky Stephen E , Richardson Robert M , Wald Ron ,   University of Toronto Acute Kidney Injury Research Group
Published: May 2012

Abstract

Background
Minimization of hemodynamic instability during renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is often challenging. We examined the relative hemodynamic tolerability of sustained low efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT) in critically ill patients with AKI. We also compared the feasibility of SLED administration with that of CRRT and intermittent hemodialysis (IHD).

Methods
This cohort study encompassed four critical care units within a single university-affiliated medical centre. 77 consecutive critically ill patients with AKI who were treated with CRRT (n = 30), SLED (n = 13) or IHD (n = 34) and completed at least two RRT sessions were included in the study. Overall, 223 RRT sessions were analyzed. Hemodynamic instability during a given session was defined as the composite of a > 20% reduction in mean arterial pressure or any escalation in pressor requirements. Treatment feasibility was evaluated based on the fraction of the prescribed therapy time that was delivered. An interrupted session was designated if < 90% of the prescribed time was administered. Generalized estimating equations were used to compare the hemodynamic tolerability of SLED vs CRRT while accounting for within-patient clustering of repeated sessions and key confounders.

Results
Hemodynamic instability occurred during 22 (56.4%) SLED and 43 (50.0%) CRRT sessions (p = 0.51). In a multivariable analysis that accounted for clustering of multiple sessions within the same patient, the odds ratio for hemodynamic instability with SLED was 1.20 (95% CI 0.58-2.47), as compared to CRRT. Session interruption occurred in 16 (16.3), 30 (34.9) and 11 (28.2) of IHD, CRRT and SLED therapies, respectively.

Conclusions
In critically ill patients with AKI, the administration of SLED is feasible and provides comparable hemodynamic control to CRRT.
Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma
Authors: Liu Zhen , Li Lixia , Yang Zhixiong , Luo Weiren , Li Xin , Yang Huiling , Yao Kaitai , Wu Bin , Fang Weiyi 
Published: May 2012

Abstract

Introduction
The aim of the present study was to analyze the expression of matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC.

Methods
Using real-time PCR, we detected the mRNA expression of MMP9 in normal nasopharyngeal tissues and nasopharyngeal carcinoma (NPC) tissues. Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 164 NPC cases (116 male and 48 female) with age ranging from 17 to 80 years (median = 48.4 years) and 32 normal nasopharyngeal tissues. Cases with greater than or equal to 6 and less than 6 of the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed.

Results
The expression level of MMP9 mRNA was markedly greater in NPC tissues than that in the nasopharyngeal tissues. Immunohistochemical analysis revealed that the protein expression of MMP9 detected in NPC tissues was higher than that in the nasopharyngeal tissues (P = 0.004). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (N classification) (P = 0.002) and clinical stage (P < 0.001) of NPC patients. Patients with higher MMP9 expression had a significantly shorter overall survival time than did patients with low MMP9 expression. Multivariate analysis suggested that the level of MMP9 expression was an independent prognostic indicator (P = 0.008) for the survival of patients with NPC.

Conclusion
High level of MMP9 expression is a potential unfavorable prognostic factor for patients with NPC.
Device for lengthening of a musculotendinous unit by direct continuous traction in the sheep
Authors: Zumstein Matthias A , Frey Eric , von Rechenberg Brigitte , Frigg Robert , Gerber Christian , Meyer Dominik C 
Published: May 2012

AbstractBackgroundRetraction, atrophy and fatty infiltration are signs subsequent to chronic rotator cuff tendon tears. They are associated with an increased pennation angle and a shortening of the muscle fibers in series. These deleterious changes of the muscular architecture are not reversible with current repair techniques and are the main factors for failed rotator cuff tendon repair. Whereas fast stretching of the retracted musculotendinous unit results in proliferation of non-contractile fibrous tissue, slow stretching may lead to muscle regeneration in terms of sarcomerogenesis. To slowly stretch the retracted musculotendinous unit in a sheep model, two here described tensioning devices have been developed and mounted on the scapular spine of the sheep using an expandable threaded rod, which has been interposed between the retracted tendon end and the original insertion site at the humeral head. Traction is transmitted in line with the musculotendinous unit by sutures knotted on the expandable threaded rod. The threaded rod of the tensioner is driven within the body through a rotating axis, which enters the body on the opposite side. The tendon end, which was previously released (16 weeks prior) from its insertion site with a bone chip, was elongated with a velocity of 1 mm/day.ResultsAfter several steps of technical improvements, the tensioner proved to be capable of actively stretching the retracted and degenerated muscle back to the original length and to withstand the external forces acting on it.ConclusionThis technical report describes the experimental technique for continuous elongation of the musculotendinous unit and reversion of the length of chronically shortened muscle.
Detailed kinetic and chemometric study of the cellulose thermal breakdown in artificially aged and non aged commercial paper. Different methods for computing activation energy as an assessment model in archaeometric applications
Authors: Marini Federico , Tomassetti Mauro , Vecchio Stefano 
Published: May 2012

Abstract

Background
The thermal oxidative degradation of aged and non aged cellulose samples of commercial paper was studied using thermogravimetry and derivative thermogravimetry under a forced air flow up to 800°C.

Results
TG and DTG data were processed using two non-isothermal-based model-fitting methods and one based on linear least squares to calculate E
a trend values, measured as a function of artificially induced sample age. The E
a trends thus obtained were compared in order to assess their potential for yielding archaeometric curves. As the trends of first two methods show an inversion of the direction between non aged cellulose samples and artificially aged samples, while the third method does not, an in-depth study was carried out using a multilinearity assumption.

Conclusions
The results are discussed and the outcomes indicate that the above cited inversion is real and not linked to the method. Additionally, it was evidenced that the number of points used for the estimation of linear least squares model parameters is of capital importance.
Xanthogranuloma of the intrasellar region presenting in pituitary dysfunction: a case report
Authors: Nishiuchi Takamasa , Murao Koji , Imachi Hitomi , Kushida Yoshio , Haba Reiji , Kawai Nobuyuki , Tamiya Takashi , Ishida Toshihiko 
Published: April 2012

Abstract

Introduction
Differentiation of cystic mass lesions of the sellar and parasellar regions may pose a diagnostic dilemma for physicians, neurosurgeons, radiologists and pathologists involved in treating patients with these entities. A considerable number of tumors previously identified as craniopharyngiomas may, in fact, have been xanthogranulomas. We report a case of pituitary dysfunction caused by xanthogranuloma of the intrasellar region.

Case presentation
A 47-year-old man of Japanese descent presented to our institution with a tumor located exclusively in the intrasellar region which manifested as severe hypopituitarism. MRI revealed a clearly defined intrasellar mass that was heterogeneously hyperintense on T1-weighted images and markedly hypointense on T2-weighted images. We preoperatively diagnosed the patient with Rathke's cleft cyst or non-functioning pituitary adenoma. Although the tumor was completely removed using a transsphenoidal approach, the improvement of the patient's endocrine function was marginal, and continued endocrine replacement therapy was needed. Postoperatively, a histological examination revealed the tumor to be a xanthogranuloma of the intrasellar region. His visual field defects and headache improved.

Conclusion
Because diagnosis depends on surgical intervention and xanthogranulomas of the intrasellar region are very rare, the natural history of xanthogranuloma is still unknown. Therefore, this entity is difficult to diagnose preoperatively. We suggest that xanthogranuloma should be included in the differential diagnosis, even in the case of sellar lesions, to formulate appropriate postoperative management and improve endocrine outcomes.
Expression of Glut-1, HIF-1α, PI3K and p-Akt in a case of ceruminous adenoma
Authors: Shen Wan-Qin , Cheng Ke-Jia , Bao Yang-Yang , Zhou Shui-Hong , Yao Hong-Tian 
Published: May 2012

Abstract

Objectives
Ceruminous adenoma of the external auditory canal (EAC) is a rare type of tumour that is diagnosed histologically. However, the clinical behaviour of these tumours remains controversial. Here, we report a case of ceruminous adenoma of the EAC and expression of a hypoxia marker.

Case report
A 78-year-old man presented with a 6-month history of recurrent otorrhoea in the right ear. Surgery was performed by the transmeatal approach with total removal of the mass. Histopathology revealed a ceruminous adenoma. Tumour cells were positive for CK, S-100 protein, Glut-1, HIF-1α, PI3K and p-Akt. There was no evidence of recurrence at last follow-up 27 months after the operation.

Conclusions
Ceruminous adenoma of the EAC is a rare tumour. The treatment of choice is wide local excision with clear margins. To our knowledge, this is the first report of Glut-1 expression and the PI3K/Akt pathway in ceruminous adenoma of the EAC.
miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells
Authors: MacQuarrie Kyle L , Yao Zizhen , Young Janet M , Cao Yi , Tapscott Stephen J 
Published: April 2012

Abstract

Background
Similar to replicating myoblasts, many rhabdomyosarcoma cells express the myogenic determination gene MyoD. In contrast to myoblasts, rhabdomyosarcoma cells do not make the transition from a regulative growth phase to terminal differentiation. Previously we demonstrated that the forced expression of MyoD with its E-protein dimerization partner was sufficient to induce differentiation and suppress multiple growth-promoting genes, suggesting that the dimer was targeting a switch that regulated the transition from growth to differentiation. Our data also suggested that a balance between various inhibitory transcription factors and MyoD activity kept rhabdomyosarcomas trapped in a proliferative state.

Methods
Potential myogenic co-factors were tested for their ability to drive differentiation in rhabdomyosarcoma cell culture models, and their relation to MyoD activity determined through molecular biological experiments.

Results
Modulation of the transcription factors RUNX1 and ZNF238 can induce differentiation in rhabdomyosarcoma cells and their activity is integrated, at least in part, through the activation of miR-206, which acts as a genetic switch to transition the cell from a proliferative growth phase to differentiation. The inhibitory transcription factor MSC also plays a role in controlling miR-206, appearing to function by occluding a binding site for MyoD in the miR-206 promoter.

Conclusions
These findings support a network model composed of coupled regulatory circuits with miR-206 functioning as a switch regulating the transition from one stable state (growth) to another (differentiation).
Increase of leishmanicidal and tubercular activities using steroids linked to aminoquinoline
Authors: Antinarelli Luciana MR , Carmo Arturene ML , Pavan Fernando R , Leite Clarice Queico F , Da Silva Adilson D , Coimbra Elaine S , Salunke Deepak B 
Published: May 2012

Abstract

Background
Aminoquinoline/steroid conjugates were synthesized based on the fact that steroid transporters have been shown to accept and carry a variety of drugs. So, in continuing our research of antileishmanial and antitubercular drugs, aminoquinoline/steroid conjugates (12, 13, and 14) were regioselectively synthesized via 1, 3-dipolar cycloaddition of alkynes 3, 5, and 7 with azide 12. The aminoquinoline/steroids conjugates were evaluated in vitro against Leishmania major and Mycobacterium tuberculosis.

Results
Regioselective synthesis of the novel aminoquinoline/steroid conjugates was achieved in very high yield. All aminoquinoline/steroid conjugates (12, 13, and 14) exhibited best results against Leishmania and M. tuberculosis than the respective alkyne intermediate structures (3, 5, and 7, respectively). Among them, the compound 12 exhibited the best activity for M. tuberculosis (MIC = 8.8 μM). This result is comparable to drugs commonly used in tuberculosis treatment. Also, for antileishmanial assay, the aminoquinoline/steroid conjugates demonstrated a significant activity against promastigote and amastigote forms of L. major.

Conclusions
Addition of a steroid group to aminoquinoline molecules enhanced the leishmanicidal and antitubercular activities. These results highlight the importance of steroids as carrier.