bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Sensitivity of Idealized Hurricane Structure and Development to the Distribution of Vertical Levels in MM5
Authors: Kimball Sytske K. , Dougherty F. Carroll 
Published: July 2006

Abstract
In the course of studying the development of hurricanes using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5), a relationship between storm intensity and the distribution of vertical levels became apparent, even when the same total number of sigma levels was used. A specific case of an idealized hurricane, on an f plane, in a quiescent environment, with constant and uniform SST of 28°C, was used to study the sensitivity of hurricane structure and evolution to the distribution of sigma levels. The distribution of vertical levels in the inflow, outflow, and middle layers of the atmosphere clearly affects the intensity, size, and structure of the storms, causing certain physical processes to be under- or overresolved. A well-resolved outflow layer is found to be necessary for proper storm intensification, while a well-resolved inflow layer does not necessarily correspond to an intense storm. In fact, when a well-resolved inflow layer is coupled with a poorly resolved outflow layer, a particularly weak storm evolves. When too few levels are assigned to the upper layer, the storm’s outflow is restricted, causing the eyewall column to become statically stable until surface fluxes can replenish low-level equivalent potential temperature content. Convection in the eyewall and compensating subsidence in the eye occur at a moderate rate and weak storms evolve. However, too few levels in the planetary boundary layer (PBL) can cause a storm to overintensify because of overestimated surface fluxes. When such a PBL is coupled with a poorly resolved outflow, the excessive surface fluxes can compensate for the stifled secondary circulation. Hence, this storm may develop to an expected intensity, but for the wrong reasons. Better guidelines for vertical-level distribution in numerical models, perhaps developed from observations of real-case hurricanes, are required.
Short-Range and Medium-Range Weather Forecasting in the Extratropics during Wintertime with and without an Interactive Ocean
Authors: Jung Thomas , Vitart Frederic 
Published: July 2006

Abstract
The ECMWF monthly forecasting system is used to investigate the impact that an interactive ocean has on short-range and medium-range weather predictions in the Northern Hemisphere extratropics during wintertime. On a hemispheric scale the predictive skill for mean sea level pressure (MSLP) with and without an interactive ocean is comparable. This can be explained by the relatively small impact that coupling has on MSLP forecasts. In fact, deterministic and ensemble integrations reveal that the magnitude of forecast error and the perturbation growth due to analysis uncertainties, respectively, by far outweigh MSLP differences between coupled and uncoupled integrations. Furthermore, no significant difference of the ensemble spread between the uncoupled and coupled system is found. The authors’ conclusions apply equally for a number of cases of rapidly intensifying extratropical cyclones in the North Atlantic region. Further experimentation with different atmospheric model versions, different horizontal atmospheric resolutions, and different ocean model formulation reveals the robustness of the findings. The results suggest that (for the cases, resolutions, and model complexities considered is this study) the benefit of using coupled atmosphere–ocean models to carry out 1–10-day MSLP forecasts is relatively small, at least in the Northern Hemisphere extratropics during wintertime.
Short-chain fatty acids induce γ-globin gene expression by displacement of a HDAC3-NCoR repressor complex
Authors: Mankidy Rishikesh , Faller Douglas V. , Mabaera Rodwell , Lowrey Christopher H. , Boosalis Michael S. , White Gary L. , Castaneda Serguei A. , Perrine Susan P. 
Published: July 2006

AbstractHigh-level induction of fetal (γ) globin gene expression for therapy of β-hemoglobinopathies likely requires local chromatin modification and dissociation of repressor complexes for γ-globin promoter activation. A novel γ-globin–inducing short-chain fatty acid derivative (SCFAD), RB7, which was identified through computational modeling, produced a 6-fold induction in a reporter assay that detects only strong inducers of the γ-globin gene promoter and in cultured human erythroid progenitors. To elucidate the molecular mechanisms used by high-potency SCFADs, chromatin immunoprecipitation (ChIP) assays performed at the human γ- and β-globin gene promoters in GM979 cells and in erythroid progenitors demonstrate that RB7 and butyrate induce dissociation of HDAC3 (but not HDAC1 or HDAC2) and its adaptor protein NCoR, specifically from the γ-globin gene promoter. A coincident and proportional recruitment of RNA polymerase II to the γ-globin gene promoter was observed with exposure to these γ-globin inducers. Knockdown of HDAC3 by siRNA induced transcription of the γ-globin gene promoter, demonstrating that displacement of HDAC3 from the γ-globin gene promoter by the SCFAD is sufficient to induce γ-globin gene expression. These studies demonstrate new dynamic alterations in transcriptional regulatory complexes associated with SCFAD-induced activation of the γ-globin gene and provide a specific molecular target for potential therapeutic intervention.
MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by α4β1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration
Authors: Redondo-Muñoz Javier , Escobar-Díaz Elizabeth , Samaniego Rafael , Terol María José , García-Marco José A. , García-Pardo Ángeles 
Published: July 2006

AbstractB-cell chronic lymphocytic leukemia (B-CLL) progression is determined by malignant cell extravasation and lymphoid tissue infiltration. We have studied the role and regulation of matrix metalloproteinase-9 (MMP-9) in B-CLL cell migration and invasion. Adhesion of B-CLL cells to the fibronectin fragment FN-H89, VCAM-1, or TNF-α–activated human umbilical vein endothelial cells (HUVECs) up-regulated MMP-9 production, measured by gelatin zymography. This effect was mediated by α4β1 integrin and required PI3-K/Akt signaling. The chemokine CXCL12 also up-regulated MMP-9, independently of α4β1 and involving ERK1/2 but not Akt activity. Accordingly, α4β1 engagement activated the PI3-K/Akt/NF-κB pathway, while CXCL12/CXCR4 interaction activated ERK1/2/c-Fos signaling. Anti–MMP-9 antibodies, the MMP-9 inhibitor TIMP-1, or transfection with 3 different MMP-9 siRNAs significantly blocked migration through Matrigel or HUVECs. Cell-associated MMP-9 was mainly at the membrane and contained the proactive and mature forms. Moreover, B-CLL cells formed podosomes upon adhesion to FN-H89, VCAM-1, or fibronectin; MMP-9 localized to podosomes in a PI3-K–dependent manner and degraded a fibronectin/gelatin matrix. Our results are the first to show that MMP-9 is physiologically regulated by α4β1 integrin and CXCL12 and plays a key role in cell invasion and transendothelial migration, thus contributing to B-CLL progression. MMP-9 could therefore constitute a target for treatment of this malignancy.
Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells
Authors: Lee Chingwei V. , Hymowitz Sarah G. , Wallweber Heidi J. , Gordon Nathaniel C. , Billeci Karen L. , Tsai Siao-Ping , Compaan Deanne M. , Yin JianPing , Gong Qian , Kelley Robert F. , DeForge Laura E. , Martin Flavius , Starovasnik Melissa A. , Fuh Germaine 
Published: July 2006

Abstract
BR3, which is expressed on all mature B cells, is a specific receptor for the B-cell survival and maturation factor BAFF (B-cell–activating factor belonging to the tumor necrosis factor [TNF] family). In order to investigate the consequences of targeting BR3 in murine models and to assess the potential of BR3 antibodies as human therapeutics, synthetic antibody phage libraries were employed to identify BAFF-blocking antibodies cross-reactive to murine and human BR3, which share 52% identity in their extracellular domains. We found an antibody, CB1, which exhibits μM affinity for murine BR3 and very weak affinity for the human receptor. CB3s, an affinity-matured variant of CB1, has sub-nM affinity for BR3 from both species. Alanine scanning and crystallographic structural analysis of the CB3s/BR3 complex reveal that CB3s mimics BAFF by interacting with a similar region of the BR3 surface. Despite this similarity in binding epitopes, CB1 variants antagonize BAFF-dependent human B-cell proliferation in vitro and are effective at reducing murine B-cell populations in vivo, showing significant promise as therapeutics for human B-cell–mediated diseases.
MANET: tracing evolution of protein architecture in metabolic networks
Authors: Kim Hee Shin , Mittenthal Jay E , Caetano-Anollés Gustavo 
Published: July 2006

AbstractBackgroundCellular metabolism can be characterized by networks of enzymatic reactions and transport processes capable of supporting cellular life. Our aim is to find evolutionarypatternsandprocessesembedded in the architecture and function of modern metabolism, using information derived from structural genomics.DescriptionThe Molecular Ancestry Network (MANET) project traces evolution of protein architecture in biomolecular networks. We describe metabolic MANET, a database that links information in the Structural Classification of Proteins (SCOP), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and phylogenetic reconstructions depicting the evolution of protein fold architecture. Metabolic MANET literally 'paints' the ancestries of enzymes derived from rooted phylogenomic trees directly onto over one hundred metabolic subnetworks, enabling the study of evolutionary patterns at global and local levels. An initial analysis of painted subnetworks reveals widespread enzymatic recruitment and an early origin of amino acid metabolism.ConclusionMANET maps evolutionary relationships directly and globally onto biological networks, and can generate and test hypotheses related to evolution of metabolism. We anticipate its use in the study of other networks, such as signaling and other protein-protein interaction networks.
Formation of functional Tat translocases from heterologous components
Authors: Hicks Matthew G , Guymer David , Buchanan Grant , Widdick David A , Caldelari Isabelle , Berks Ben C , Palmer Tracy 
Published: July 2006

Abstract

Background
The Tat pathway transports folded proteins across the cytoplasmic membrane of bacteria and the thylakoid membrane of plants. In Eschericha coli, Tat transport requires the integral membrane proteins TatA, TatB and TatC. In this study we have tested the ability of tat genes from the eubacterial species Pseudomonas syringae, Streptomyces coelicolor and Aquifex aeolicus, to compensate for the absence of the cognate E. coli tat gene, and thus to form functional Tat translocases with E. coli Tat components.

Results
All three subunits of the Tat system from the Gram positive organism Streptomyces coelicolor were able to form heterologous translocases with substantive Tat transport activity. However, only the TatA and TatB proteins of Pseudomonas syringae were able to functionally interact with the E. coli Tat system even though the two organisms are closely related. Of the Tat components from the phylogenetically distant hyperthermophillic bacterium Aquifex aeolicus only the TatA proteins showed any detectable level of heterologous functionality. The heterologously expressed TatA proteins of S. coelicolor and A. aeolicus were found exclusively in the membrane fraction.

Conclusion
Our results show that of the three Tat proteins, TatA is most likely to show cross-species complementation. By contrast, TatB and TatC do not always show cross-complementation, probably because they must recognise heterologous signal peptides. Since heterologously-expressed S. coelicolor TatA protein was functional and found only in the membrane fraction, it suggests that soluble forms of Streptomyces TatA reported by others do not play a role in protein export.
Familial deletion 18p syndrome: case report
Authors: Maranda Bruno , Lemieux Nicole , Lemyre Emmanuelle 
Published: July 2006

Abstract

Background
Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases.

Case presentation
The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18)(p11.2). Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p) are fertile and seem to have a normal miscarriage rate.

Conclusion
Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.
Use of filter paper stored dried blood for measurement of triglycerides
Authors: Quraishi Rizwana , Lakshmy Ramakrishnan , Prabhakaran Dorairaj , Mukhopadhyay Ashok Kumar , Jailkhani Bansilal 
Published: July 2006

Abstract
Adaptation of assays on dried blood has advantages of ease of collection, transportation, minimal invasiveness and requirement of small volume. A method for extraction and estimation of triglyceride from blood spots dried on filter paper (Whatman no. 3) has been developed. A single dried blood spot containing 10 μL blood was used. Triglyceride was efficiently extracted in methanol from blood dried on filter paper by incubation at 37°C for two hours with gentle shaking. For the estimation, a commercially available enzymatic method was used. Blood spot assays showed mean intra and inter assay coefficient of variance of 6.0% and 7.4% respectively. A comparison of paired whole blood spots and plasma samples (n = 75, day 0) gave an intraclass correlation of 0.96. The recovery was 99.6%. The dried blood triglyceride concentrations were stable for one month when the filter discs were stored at room temperature (16–28°C). Storage of filters at 4°C extended the stability and triglycerides could be quantatively recovered after 3 months of storage.
Oxidative stress increases Fas ligand expression in endothelial cells
Authors: Suzuki Mayumi , Aoshiba Kazutetsu , Nagai Atsushi 
Published: July 2006

AbstractBackgroundFas ligand (FasL) induces apoptosis in Fas-bearing target cells, such as leukocytes, and up-regulation of FasL expression on the endothelium may contribute to anti-inflammatory reactions that attenuate leukocyte extravasation during inflammation. Since oxidants generated during inflammation and cigarette smoking may modulate endothelial function, we examined the effect of H2O2and cigarette smoke on endothelial FasL expression.MethodsHuman umbilical vein endothelial cells (HUVECs) were exposed to nontoxic concentrations of H2O2and cigarette smoke extracts (CSE). Membrane FasL expression was assessed by immunostaining with anti-FasL antibody followed by either monolayer-cell-based spectrofluorimetry or flow cytometry. Soluble FasL in culture supernatants was measured by enzyme-linked immunosorbent assay. For the cytotoxic assay, HUVECs were exposed to H2O2and co-cultured with neutrophils. Neutrophils were stained by a peroxidase/diaminobenzidine-based reaction, and apoptosis was evaluated on the basis of nuclear morphology after Giemsa staining. To analyze in vitro FasL expression in arteries, rat thoracic aortas were incubated with H2O2, and paraffin-embedded sections were prepared for immunohistochemistry with anti-FasL antibody.ResultsExposure of HUVECs to H2O2dose-dependently increased their levels of both membrane and soluble forms of FasL expression. CSE exposure also caused increased levels of FasL expression, but the increase was partially inhibited by the addition of catalase. When co-cultured with neutrophils, HUVECs exposed to H2O2significantly promoted neutrophil apoptosis. Rat thoracic aortas incubated with H2O2exhibited increased FasL expression on their endothelium.ConclusionLow levels of oxidative stress increase FasL expression on endothelial cells, thereby potentially reducing leukocyte extravasation and tissue damage.
Flow-cytometric assessment of cellular poly(ADP-ribosyl)ation capacity in peripheral blood lymphocytes
Authors: Kunzmann Andrea , Liu Dan , Annett Kathryn , Malaisé Muriel , Thaa Bastian , Hyland Paul , Barnett Yvonne , Bürkle Alexander 
Published: July 2006

Abstract

Background
Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins catalysed by poly(ADP-ribose) polymerases (PARPs), using NAD+ as a substrate. Activation of PARP-1 is in immediate response to DNA damage generated by endogenous and exogenous damaging agents. It has been implicated in several crucial cellular processes including DNA repair and maintenance of genomic stability, which are both intimately linked with the ageing process. The measurement of cellular poly(ADP-ribosyl)ation capacity, defined as the amount of poly(ADP-ribose) produced under maximal stimulation, is therefore relevant for research on ageing, as well as for a variety of other scientific questions.

Results
This paper reports a new, robust protocol for the measurement of cellular poly(ADP-ribosyl)ation capacity in PBMC or Jurkat T-cells using flow cytometry, based on a previously established immuno-dot-blot assay. In order to validate the new assay, we determined the dose-response curve of 3-aminobenzamide, a well-known competitive PARP inhibitor, and we derived an IC50 that is very close to the published value. When testing a set of PBMC samples taken from fifteen healthy young human donors, we could confirm the presence of a substantial interindividual variation, as previously observed using a radiometric assay.

Conclusion
The methodology described in this paper should be generally useful for the determination of cellular poly(ADP-ribosyl)ation capacity in a wide variety of settings, especially for the comparison of large sets of samples, such as population studies. In contrast to previously published radiometric or immuno-dot-blot assays, the new FACS-based method allows (i) selective analysis of mononuclear cells by gating and (ii) detection of a possible heterogeneity in poly(ADP-ribosyl)ation capacity between cells of the same type.
Cardiomyopathy, familial dilated
Authors: Taylor Matthew RG , Carniel Elisa , Mestroni Luisa 
Published: July 2006

AbstractDilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed). In many cases the disease is inherited and is termedfamilialDCM (FDC). FDC may account for 20–48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise) and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed left ventricular ejection fraction have a low survival rate and may require heart transplant.
Cancer Genetic Testing and Assisted Reproduction
Authors: Offit Kenneth , Kohut Kelly , Clagett Bartholt , Wadsworth Eve A. , Lafaro Kelly J. , Cummings Shelly , White Melody , Sagi Michal , Bernstein Donna , Davis Jessica G. 
Published: July 2006

Purpose Because of increasing uptake of cancer genetic testing and the improving survival of young patients with cancer, health care practitioners including oncologists will increasingly be asked about options for assisted reproduction by members of families affected by hereditary cancer syndromes. Among these reproductive options, preimplantation genetic diagnosis (PGD) offers the opportunity to select embryos without familial cancer-predisposing mutations. Methods A review of the published literature supplemented by a survey of PGD centers in the United States. Results Prenatal diagnosis and/or embryo selection after genetic testing has already been performed in the context of more than a dozen familial cancer syndromes, including the common syndromes of genetic predisposition to colon and breast cancer. Conclusion While constituting new reproductive options for families affected by cancer, the medical indications and ethical acceptance of assisted reproductive technologies for adult-onset cancer predisposition syndromes remain to be defined. Continued discussion of the role of PGD in the reproductive setting is needed to inform the responsible use of these technologies to decrease the burden of heritable cancers.