bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat hematologic emergencies in adults with acute leukemia
Authors: Zuckerman Tsila , Ganzel Chezi , Tallman Martin S. , Rowe Jacob M. 
Published: June 2012

Abstract
Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. Whereas clinical trials form the backbone for the management of acute leukemia, emergent clinical situations, predictable or not, are common and do not readily lend themselves to clinical trial evaluation. Furthermore, practice guidelines are often lacking. Not only are prospective trials impractical because of the emergent nature of the issue at hand, but clinicians are often reluctant to randomize such patients. Extensive practical experience is crucial and, even if there is no consensus, management of such emergencies should be guided by an understanding of the underlying pathophysiologic mechanisms.
A note on the existence and uniqueness of the solutions to SFDES
Authors: Cho Yeol JE , Dragomir Sever S , Kim Young-Ho 
Published: June 2012

Abstract
In this paper, we establish a new proof of the existence and uniqueness of solution to stochastic functional differential equations with infinite delay at phase space BC((-∞, 0]: R

d
) which denotes the family of bounded continuous R

d
-valued functions φ defined on (-∞, 0] with norm ||φ|| = sup-∞ < θ≤0|φ(θ)|.

Mathematics Subject Classification (2000): 60H05, 60H10.
Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton
Authors: DeLaurier April , Nakamura Yukio , Braasch Ingo , Khanna Vishesh , Kato Hiroyuki , Wakitani Shigeyuki , Postlethwait John H , Kimmel Charles B 
Published: June 2012

Abstract
Background
Histone deacetylase-4 (Hdac4) is a class II histone deacetylase that inhibits the activity of transcription factors. In humans, HDAC4 deficiency is associated with non-syndromic oral clefts and brachydactyly mental retardation syndrome (BDMR) with craniofacial abnormalities.

Results
We identify hdac4 in zebrafish and characterize its function in craniofacial morphogenesis. The gene is present as a single copy, and the deduced Hdac4 protein sequence shares all known functional domains with human HDAC4. The zebrafish hdac4 transcript is widely present in migratory cranial neural crest (CNC) cells of the embryo, including populations migrating around the eye, which previously have been shown to contribute to the formation of the palatal skeleton of the early larva. Embryos injected with hdac4 morpholinos (MO) have reduced or absent CNC populations that normally migrate medial to the eye. CNC-derived palatal precursor cells do not recover at the post-migratory stage, and subsequently we found that defects in the developing cartilaginous palatal skeleton correlate with reduction or absence of early CNC cells. Palatal skeletal defects prominently include a shortened, clefted, or missing ethmoid plate, and are associated with a shortening of the face of young larvae.

Conclusions
Our results demonstrate that Hdac4 is a regulator of CNC-derived palatal skeletal precursors during early embryogenesis. Cleft palate resulting from HDAC4 mutations in human patients may result from defects in a homologous CNC progenitor cell population.
Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells
Authors: Tebaldi Toma , Re Angela , Viero Gabriella , Pegoretti Ilaria , Passerini Andrea , Blanzieri Enrico , Quattrone Alessandro 
Published: June 2012

Abstract

Background
The classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome) and the polysome-associated mRNAs (the translatome) after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs.

Results
Triggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels.

Conclusions
We propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression.
Efficient Production of an Engineered Apoptin from Chicken Anemia Virus in a Recombinant E. coli for Tumor Therapeutic Applications
Authors: Lee Meng-Shiou , Sun Fang-Chun , Huang Chi-Hung , Lien Yi-Yang , Feng Shin-Huei , Lai Guan-Hua , Lee Meng-Shiunn , Chao Jung , Chen Hsi-Jien , Tzen Jason T C , Cheng Hao-Yuan 
Published: June 2012

Abstract

Background
Apoptin, a nonstructural protein encoded by the VP3 gene of chicken anemia virus (CAV), has been shown to not only induce apoptosis when introduced into the precursors of chicken thymocytes, but has been found to specifically kill human cancer cells, tumor cell and transformed cells without affecting the proliferation of normal cells. This tumor-specific apoptotic characteristic of the protein potentially may allow the development of a protein drug that has applications in tumor therapy. However, several major problems, which include poor expression and poor protein solubility, have hampered the production of apoptin in bacteria.

Results
Significantly increased expression of recombinant full-length apoptin that originated from chicken anemia virus was demonstrated using an E. coli expression system. The CAV VP3 gene was fused with a synthetic sequence containing a trans-acting activator of transcription (TAT) protein transduction domain (PTD). The resulting construct was cloned into various different expression vectors and these were then expressed in various E. coli strains. The expression of the TAT-Apoptin in E. coli was significantly increased when TAT-Apoptin was fused with GST-tag rather than a His-tag. When the various rare amino acid codons of apoptin were optimized, the expression level of the GST-TAT-Apoptinopt in E. coli BL21(DE3) was significantly further increased. The highest protein expression level obtained was 8.33 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 4 h at 25 °C. Moreover, approximately 90% of the expressed GST-TAT-Apoptinopt under these conditions was soluble. After purification by GST affinity chromatography, the purified recombinant TAT-Apoptinopt protein was used to evaluate the recombinant protein’s apoptotic activity on tumor cells. The results demonstrated that the E. coli-expressed GST-TAT-apoptinopt showed apoptotic activity and was able to induce human premyelocytic leukemia HL-60 cells to enter apoptosis.

Conclusions
On expression in E. coli, purified recombinant TAT-Apoptinopt that has been fused to a GST tag and had its codons optimized, was found to have great potential. This protein may in the future allow the development of a therapeutic protein that is able to specifically kill tumor cells.
Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis
Authors: Lin Shin-Jen , Ho Hsin-Chiu , Lee Yi-Fen , Liu Ning-Chun , Liu Su , Li Gonghui , Shyr Chih-Rong , Chang Chawnshang 
Published: June 2012

Abstract

Background
Early studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear.

Methods
We generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA) were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin.

Results
We first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner.

Conclusions
Together, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities.
Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis
Authors: Biswas Sangita , Benedict Stephen H , Lynch Sharon G , LeVine Steven M 
Published: June 2012

AbstractCorticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis.
First isolation and characterization of Chryseobacterium shigense from rainbow trout
Authors: Zamora Leydis , Vela Ana I , Palacios Mª Angel , Domínguez Lucas , Fernández-Garayzábal José Francisco 
Published: June 2012

Abstract

Background
There have been an increasing number of infections in fish associated with different species of Chryseobacterium, being considered potentially emerging pathogens. Nevertheless the knowledge of the diversity of species associated with fish disease is partial due to the problems for a correct identification at the species level based exclusively on phenotypic laboratory methods.

Results

Chryseobacterium shigense was isolated from the liver, kidney and gills of diseased rainbow trout in different disease episodes that occurred in a fish farm between May 2008 and June 2009. Identity of the isolates was confirmed by 16 S rRNA gene sequencing and phenotypic characterization. Isolates represented a single strain as determined by random amplified polymorphic DNA analysis.

Conclusions
This is the first description of the recovery of C. shigense from clinical specimens in trout, a very different habitat to fresh lactic acid beverage where it was initially isolated.
Comparative study on factors affecting anaerobic digestion of agricultural vegetal residues
Authors: Cioabla Adrian Eugen , Ionel Ioana , Dumitrel Gabriela-Alina , Popescu Francisc 
Published: June 2012

Abstract

Background
Presently, different studies are conducted related to the topic of biomass potential to generate through anaerobic fermentation process alternative fuels supposed to support the existing fossil fuel resources, which are more and more needed, in quantity, but also in quality of so called green energy. The present study focuses on depicting an optional way of capitalizing agricultural biomass residues using anaerobic fermentation in order to obtain biogas with satisfactory characteristics.. The research is based on wheat bran and a mix of damaged ground grains substrates for biogas production.

Results
The information and conclusions delivered offer results covering the general characteristics of biomass used , the process parameters with direct impact over the biogas production (temperature regime, pH values) and the daily biogas production for each batch relative to the used material.

Conclusions
All conclusions are based on processing of monitoring process results , with accent on temperature and pH influence on the daily biogas production for the two batches. The main conclusion underlines the fact that the mixture batch produces a larger quantity of biogas, using approximately the same process conditions and input, in comparison to alone analyzed probes, indicating thus a higher potential for the biogas production than the wheat bran substrate.
Adrian Eugen Cioabla, Ioana Ionel, Gabriela-Alina Dumitrel and Francisc Popescu contributed equally to this work
Development of a luciferase-based reporter of transcriptional gene silencing that enables bidirectional mutant screening in Arabidopsis thaliana
Authors: Won So Youn , Li Shengben , Zheng Binglian , Zhao Yuanyuan , Li Dongming , Zhao Xin , Yi Huilan , Gao Lei , Dinh Thanh Theresa , Chen Xuemei 
Published: June 2012

AbstractBackgroundCytosine methylation is an important chromatin modification that maintains genome integrity and regulates gene expression through transcriptional gene silencing. Major players inde novomethylation guided by siRNAs (known as RNA-directed DNA methylation, or RdDM), maintenance methylation, and active demethylation have been identified inArabidopsis. However, active demethylation only occurs at a subset of RdDM loci, raising the question of how the homeostasis of DNA methylation is achieved at most RdDM loci. To identify factors that regulate the levels of cytosine methylation, we aimed to establish a transgenic reporter system that allows for forward genetic screens inArabidopsis.ResultsWe introduced a dual35 Spromoter (d35S) drivenluciferasereporter,LUCH, intoArabidopsisand isolated a line with a moderate level of luciferase activity.LUCHproduced transgene-specific 24 nucleotide siRNAs and itsd35Scontained methylated cytosine in CG, CHG and CHH contexts. Treatment of the transgenic line with an inhibitor of cytosine methylation de-repressed luciferase activity. Mutations in several components of the RdDM pathway but not the maintenance methylation genes resulted in reducedd35Smethylation, especially CHH methylation, and de-repression of luciferase activity. A mutation inMOM1, which is known to cooperate with RdDM to silence transposons, reducedd35SDNA methylation and de-repressedLUCHexpression. A mutation in ROS1, a cytosine demethylation enzyme, increasedd35Smethylation and reducedLUCHexpression.ConclusionWe developed a luciferase-based reporter,LUCH, which reports both DNA methylation directed by small RNAs and active demethylation by ROS1 inArabidopsis. The moderate basal level ofLUCHexpression allows for bi-directional genetic screens that dissect the mechanisms of DNA methylation as well as demethylation.
Interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with T-cell and B-cell activation
Authors: Hartgring Sarita AY , Willis Cynthia R , Bijlsma Johannes WJ , Lafeber Floris PJG , van Roon Joel AG 
Published: June 2012

Abstract

Introduction

We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved.

Methods

Mice received multiple injections with IL-7 or phosphate-buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B-cell subsets were assessed, as well as ex vivo production of interferon-γ (IFN-γ), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling.

Results

IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7-increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19+ B cells and CD19+/GL7+ germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-γ-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-γ and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1γ, MIP-3β, lymphotactin, MDC, and MCP-5).

Conclusions

In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies.
Retinoblastoma protein induction by HIV viremia or CCR5 in monocytes exposed to HIV-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study
Authors: Gekonge Bethsebah , Raymond Andrea D , Yin Xiangfan , Kostman Jay , Mounzer Karam , Collman Ronald G , Showe Louise , Montaner Luis J 
Published: June 2012

Abstract
Identification of Rb1 induction in chronic asymptomatic HIV-1 infection as a mediator of apoptosis resistance in monocytes, in association with protective autophagy.
We have previously described an antiapoptotic steady-state gene expression profile in circulating human monocytes from asymptomatic viremic HIV+ donors, but the mechanism associated with this apoptosis resistance remains to be fully elucidated. Here, we show that Rb1 activation is a dominant feature of apoptosis resistance in monocytes exposed to HIV-1 in vivo (as measured ex vivo) and in vitro. Monocytes from asymptomatic viremic HIV+ individuals show a positive correlation between levels of hypophosphorylated (active) Rb1 and VL in conjunction with increases in other p53-inducible proteins associated with antiapoptosis regulation, such as p21 and PAI-1 (SERPINE1), when compared with circulating monocytes from uninfected donors. Monocytes exposed in vitro to HIV-1 R5 isolates but not X4 isolates showed lower caspase-3 activation after apoptosis induction, indicating a role for the CCR5 signaling pathway. Moreover, monocytes exposed to R5 HIV-1 or MIP-1β induced Rb1 and p21 expression and an accumulation of autophagy markers, LC3 and Beclin. The inhibition of Rb1 activity in HIV-1 R5 viral-exposed monocytes using siRNA led to increased apoptosis sensitivity, thereby confirming a central role for Rb1 in the antiapoptotic phenotype. Our data identify Rb1 induction in chronic asymptomatic HIV-1 infection as a mediator of apoptosis resistance in monocytes in association with protective autophagy and contributing to monocyte survival during immune activation and/or HIV-1 viremia.
Increased Marrow Adiposity in Premenopausal Women with Idiopathic Osteoporosis
Authors: Cohen Adi , Dempster David W. , Stein Emily M. , Nickolas Thomas L. , Zhou Hua , McMahon Donald J. , Müller Ralph , Kohler Thomas , Zwahlen Alexander , Lappe Joan M. , Young Polly , Recker Robert R. , Shane Elizabeth 
Published: June 2012

Abstract

Context:
We have previously reported that premenopausal women with idiopathic osteoporosis based on fractures (IOP) or idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness.

Objective:
Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number.

Design:
We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by three-dimensional micro-computed tomography and two-dimensional quantitative histomorphometry to assess marrow adipocyte number, perimeter, and area.

Results:
IOP and ILBMD subjects did not differ with regard to any adipocyte parameter, and thus results were combined. Subjects had substantially higher adipocyte number (by 22%), size (by 24%), and volume (by 26%) than controls (P &lt; 0.0001 for all). Results remained significant after adjusting for age, body mass index, and bone volume. Controls demonstrated expected direct associations between marrow adiposity and age and inverse relationships between marrow adiposity and bone formation, volume, and microstructure measures. No such relationships were observed in the subjects.

Conclusions:
Higher marrow adiposity and the absence of expected relationships between marrow adiposity and bone microstructure and remodeling in women with IOP or ILBMD suggest that the relationships between fat and bone are abnormal; excess marrow fat may not arise from a switch from the osteoblast to the adipocyte lineage in this disorder. Whether excess marrow fat contributes to the pathogenesis of this disorder remains unclear.