bluuebunny/crossref_metadata_2025 huggingface dataset:
“1D+4DVAR” Assimilation of NCEP Stage-IV Radar and Gauge Hourly Precipitation Data at ECMWF
Authors: Lopez Philippe , Bauer Peter
Published: July 2007

The one- plus four-dimensional variational data assimilation (“1D+4DVAR”) method currently run in operations at ECMWF with rain-affected radiances from the Special Sensor Microwave Imager is used to study the potential impact of assimilating NCEP stage-IV analyses of hourly accumulated surface precipitation over the U.S. mainland. These data are a combination of rain gauge measurements and observations from the high-resolution Doppler Next-Generation Weather Radars. Several 1D+4DVAR experiments have been run over a month in spring 2005. First, the quality of the precipitation forecasts in the control experiment is assessed. Then, it is shown that the impact of the assimilation of the additional rain observations on global scores of dynamical fields and temperature is rather neutral, while precipitation scores are improved for forecast ranges up to 12 h. Additional 1D+4DVAR experiments in which all moisture-affected observations are removed over the United States demonstrate that the NCEP stage-IV precipitation data on their own can clearly be beneficial to the analyses and subsequent forecasts of the moisture field. This result suggests that the potential impact of precipitation observations is overshadowed by the influence of other high-quality humidity observations, in particular, radiosondes. It also confirms that the assimilation of precipitation observations has the ability to improve the quality of moisture analyses and forecasts in data-sparse regions. Finally, the limitations inherent in the current assimilation of precipitation data, their implications for the future, and possible ways of improvement are discussed.
The “Triple Point” on 24 May 2002 during IHOP. Part II: Ground-Radar and In Situ Boundary Layer Analysis of Cumulus Development and Convection Initiation
Authors: Ziegler Conrad L. , Rasmussen Erik N. , Buban Michael S. , Richardson Yvette P. , Miller L. Jay , Rabin Robert M.
Published: July 2007

Cumulus formation and convection initiation are examined near a cold front–dryline “triple point” intersection on 24 May 2002 during the International H2O Project (IHOP). A new Lagrangian objective analysis technique assimilates in situ measurements using time-dependent Doppler-derived 3D wind fields, providing output 3D fields of water vapor mixing ratio, virtual potential temperature, and lifted condensation level (LCL) and water-saturated (i.e., cloud) volumes on a subdomain of the radar analysis grid. The radar and Lagrangian analyses reveal the presence of along-wind (i.e., longitudinal) and cross-wind (i.e., transverse) roll circulations in the boundary layer (BL). A remarkable finding of the evolving radar analyses is the apparent persistence of both transverse rolls and individual updraft, vertical vorticity, and reflectivity cores for periods of up to 30 min or more while moving approximately with the local BL wind. Satellite cloud images and single-camera ground photogrammetry imply that clouds tend to develop either over or on the downwind edge of BL updrafts, with a tendency for clouds to elongate and dissipate in the downwind direction relative to cloud layer winds due to weakening updrafts and mixing with drier overlying air. The Lagrangian and radar wind analyses support a parcel continuity principle for cumulus formation, which requires that rising moist air parcels achieve their LCL before moving laterally out of the updraft. Cumuli form within penetrative updrafts in the elevated residual layer (ERL) overlying the moist BL east of the triple point, but remain capped by a convection inhibition (CIN)-bearing layer above the ERL. Dropsonde data suggest the existence of a convergence line about 80 km east of the triple point where deep lifting of BL moisture and locally reduced CIN together support convection initiation.
Lower-Tropospheric Height Tendencies Associated with the Shearwise and Transverse Components of Quasigeostrophic Vertical Motion
Authors: Martin Jonathan E.
Published: July 2007

The recent suggestion that lower-tropospheric cyclogenesis is predominantly a result of column stretching associated with the updraft portion of the shearwise quasigeostrophic (QG) vertical motion is quantified through direct calculation of 900-hPa height tendencies via the QG vorticity equation. Comparison of the separate lower-tropospheric height tendencies associated with the shearwise and transverse portions of QG omega in a robust cyclogenesis event demonstrates that the shearwise updraft drives the largest part (>80%) of the cyclogenetic height falls at least through the end of the mature stage of the life cycle. The lower-tropospheric height falls and vorticity production near the sea level pressure minimum of the occluded surface cyclone are driven nearly equally by shearwise and transverse updrafts.
Microphysical and Radiative Effects of Ice Clouds on Tropical Equilibrium States: A Two-Dimensional Cloud-Resolving Modeling Study
Authors: Ping Fan , Luo Zhexian , Li Xiaofan
Published: July 2007

The microphysical and radiative effects of ice clouds on tropical equilibrium states are investigated based on three two-dimensional cloud-resolving simulations imposed by zero vertical velocity and time-invariant zonal wind and sea surface temperature. An experiment without ice microphysics (ice microphysical and radiative effects; C00), another experiment without ice radiative effects (CI0), and the control experiment (CIR) are carried out. The model with cyclic lateral boundaries is integrated for 40 days to reach equilibrium states in all experiments. CI0 produces a colder and drier equilibrium state than CIR and C00 do through generating a larger IR cooling, a larger vapor condensation rate, and consuming a larger amount of water vapor. A larger surface rain rate occurs in CI0 than in CIR and C00. The ice radiative effects on thermodynamic equilibrium states are stronger than the ice microphysical effects so that the exclusion of ice microphysics yields a colder and drier equilibrium state in C00 than in CIR. The ice radiative effects and the ice microphysical effects on surface rainfall processes are largely offset, which leads to similar zonal-mean surface rain rates in C00 and CIR.
Electrical and Polarimetric Radar Observations of a Multicell Storm in TELEX
Authors: Bruning Eric C. , Rust W. David , Schuur Terry J. , MacGorman Donald R. , Krehbiel Paul R. , Rison William
Published: July 2007

On 28–29 June 2004 a multicellular thunderstorm west of Oklahoma City, Oklahoma, was probed as part of the Thunderstorm Electrification and Lightning Experiment field program. This study makes use of radar observations from the Norman, Oklahoma, polarimetric Weather Surveillance Radar-1988 Doppler, three-dimensional lightning mapping data from the Oklahoma Lightning Mapping Array (LMA), and balloon-borne vector electric field meter (EFM) measurements. The storm had a low flash rate (30 flashes in 40 min). Four charge regions were inferred from a combination of LMA and EFM data. Lower positive charge near 4 km and midlevel negative charge from 4.5 to 6 km MSL (from 0° to −6.5°C) were generated in and adjacent to a vigorous updraft pulse. Further midlevel negative charge from 4.5 to 6 km MSL and upper positive charge from 6 to 8 km (from −6.5° to −19°C) were generated later in quantity sufficient to initiate lightning as the updraft decayed. A negative screening layer was present near the storm top (8.5 km MSL, −25°C). Initial lightning flashes were between lower positive and midlevel negative charge and started occurring shortly after a cell began lofting hydrometeors into the mixed phase region, where graupel was formed. A leader from the storm’s first flash avoided a region where polarimetric radar suggested wet growth and the resultant absence of noninductive charging of those hydrometeors. Initiation locations of later flashes that propagated into the upper positive charge tracked the descending location of a polarimetric signature of graupel. As the storm decayed, electric fields greater than 160 kV m−1 exceeded the minimum threshold for lightning initiation suggested by the hypothesized runaway breakdown process at 5.5 km MSL, but lightning did not occur. The small spatial extent (≈100 m) of the large electric field may not have been sufficient to allow runaway breakdown to fully develop and initiate lightning.
Winter Lightning and North Atlantic Oscillation
Authors: de Pablo Fernando , Soriano Luis Rivas
Published: July 2007

The relationship between the North Atlantic Oscillation (NAO) and total (in cloud and cloud to ground) lightning activity during the wintertime (December to March) is analyzed. Lightning data from the Optical Transient Detector were used and were studied in the North Atlantic and western European area. The southern half of the area analyzed (latitudes lower than ∼50°N) was observed to have an increased (decreased) lightning flash rate associated with negative (positive) NAO index values. The opposite relationship was found when the northern half (latitudes higher than ∼50°N) was considered. In both cases, the effect of the NAO on the lightning activity was stronger over the eastern area analyzed. Low (clearly <1) absolute values of the NAO index seem to be associated with minimum lightning activity.
The Dryline on 22 May 2002 during IHOP: Ground-Radar and In Situ Data Analyses of the Dryline and Boundary Layer Evolution
Authors: Buban Michael S. , Ziegler Conrad L. , Rasmussen Erik N. , Richardson Yvette P.
Published: July 2007

On the afternoon and evening of 22 May 2002, high-resolution observations of the boundary layer (BL) and a dryline were obtained in the eastern Oklahoma and Texas panhandles during the International H2O Project. Using overdetermined multiple-Doppler radar syntheses in concert with a Lagrangian analysis of water vapor and temperature fields, the 3D kinematic and thermodynamic structure of the dryline and surrounding BL have been analyzed over a nearly 2-h period. The dryline is resolved as a strong (2–4 g kg−1 km−1) gradient of water vapor mixing ratio that resides in a nearly north–south-oriented zone of convergence. Maintained through frontogenesis, the dryline is also located within a gradient of virtual potential temperature, which induces a persistent, solenoidally forced secondary circulation. Initially quasi-stationary, the dryline retrogrades to the west during early evening and displays complicated substructures including small wavelike perturbations that travel from south to north at nearly the speed of the mean BL flow. A second, minor dryline has similar characteristics to the first, but has weaker gradients and circulations. The BL adjacent to the dryline exhibits complicated structures, consisting of combinations of open cells, horizontal convective rolls, and transverse rolls. Strong convergence and vertical motion at the dryline act to lift moisture, and high-based cumulus clouds are observed in the analysis domain. Although the top of the analysis domain is below the lifted condensation level height, vertical extrapolation of the moisture fields generally agrees with cloud locations. Mesoscale vortices that move along the dryline induce a transient eastward dryline motion due to the eastward advection of dry air following misocyclone passage. Refractivity-based moisture and differential reflectivity analyses are used to help interpret the Lagrangian analyses.
Tensile Properties of Silk from Endemic New Zealand Spiders
Authors: Carr Debra J. , Lowe Bronwyn , Bishop Phillip J. , Niven Brian E. , Gould Scot A. C.
Published: July 2007

Differences in tensile properties were measured among individuals from four species of endemic New Zealand spiders that occupy different positions on the phylogenetic tree. The lowest load, stiffness, and work, but highest strain was measured for Porrhothele antipodiana, an ancestral Mygalomorph. In comparison, the highest load, stiffness, and work, and lowest strain were measured for a modern day Theridiid Cambridgea foliata. The gauge length of the specimen and the speed of the test significantly affected the tensile property data values measured.
Rural Women Walking for Health
Authors: Perry Cindy K. , Rosenfeld Anne G. , Kendall Judith
Published: July 2007

The purpose of this qualitative study is to describe rural women's barriers and motivators for participation in a walking program. Twenty rural women, ages 22 to 65, participated in a 12-week walking program. Data from field notes and focus groups were analyzed using qualitative content analysis. Data were inductively coded, codes were categorized into themes, and themes were classified as barriers or motivators to adopting a walking program. Three main barriers are identified: balancing family and self, chronic illness gets in the way of routine, and illness or injury breaks routine. Seven motivators are identified: being part of a group, group camaraderie, learning, pacesetter, seeing progress, energizing, and I am a walker. Women report that family responsibilities are a powerful and pervasive barrier. Motivators center on the importance of group interaction. This qualitative study increases our understanding of rural women's barriers and motivators to embarking on and sustaining a regular walking routine.
Factors Affecting Environmental Behavior in Micro-enterprises
Authors: Mir Debby F. , Feitelson Eran
Published: July 2007

The study assesses conditions and variables affecting environmental behavior in small service family firms, and questions the relevance of SME and small business studies for micro-enterprises. All Jerusalem laundry (61) and motor vehicle repair (46) firms were surveyed, because of their aggregate environmental impact, spatial distribution, and literature on intervention programs. A key finding was the lack of correlation between environmental awareness and action. However, despite limited social and government pressure and support services, traditional micro-enterprises undertook significant environmental actions when feasible, almost regardless of owner attributes or motivations. Micro-enterprises responded selectively to non-environmental government agencies in frequent contact. Market opportunities include contractual relationships with large companies requiring professional (hence environmental) standards, and new efficient or environmental equipment and products. There was little or no market pressure and few niche markets. Firms that adopted environmental measures returned to illegal practices when environmental agencies withdrew subsidies.
Self-Reported Treatment Patterns in Patients With Sturge-Weber Syndrome and Migraines
Authors: Kossoff Eric H. , Balasta Marguerite , Hatfield Laura M. , Lehmann Christoph U. , Comi Anne M.
Published: July 2007

Migraine is common in patients with Sturge-Weber syndrome, yet treatment options are poorly described. An Internet-based questionnaire was completed anonymously by 104 Sturge-Weber syndrome patients, 74 of whom reported experiencing migraines (median age, 25 years; range, 3-64 years). Sixteen (22%) subjects self-reported trying triptans. Five of 12 (42%) describing triptan response believed they were very efficacious (median time of onset of 26 minutes), compared to 13 of 65 (20%) using over-the-counter analgesics ( P = .08). Eighty-eight percent (14/16) of triptan users self-reported that when they do not use medications, migraines had a moderate to severe impact on their quality of life; however, while taking triptans, only 50% (7/14) of users reported such an impact ( P = .03). Two patients using triptans reported transient unilateral weakness. Of the 26 patients (35%) who received daily preventative medications, 80% experienced improved quality of life. In addition, only 10 of 24 (42%) reported a significant negative impact of migraines on quality of life with daily preventative use, compared to 22 of 26 (85%) without their use ( P = .002). Sturge-Weber syndrome patients with migraines are using triptans and preventative agents and self-reporting good efficacy. The small sample size precludes any safety analysis, however, and future prospective trials of both treatment options are needed.
Laparoscopic Nissen Fundoplication During Gastrostomy Tube Placement and Noninvasive Ventilation May Improve Survival in Type I and Severe Type II Spinal Muscular Atrophy
Authors: Yuan Nanci , Wang Ching H. , Trela Anthony , Albanese Craig T.
Published: July 2007

Progressive respiratory muscle weakness with bulbar involvement is the main cause of morbidity and mortality in type I and severe type II spinal muscular atrophy. Noninvasive positive pressure ventilation techniques coupled with laparoscopic gastrointestinal procedures may allow for improved morbidity and mortality. The authors present a series of 7 spinal muscular atrophy patients (6 type I and 1 severe type II) who successfully underwent laparoscopic gastrostomy tube insertion coupled with Nissen fundoplication and early postoperative extubation using noninvasive positive pressure ventilation techniques. The authors measured the length of survival and the frequencies of pneumonia and hospitalization before and after surgery as outcomes of these new surgical and medical interventions. All 7 patients had respiratory symptoms (unmanageable oropharyngeal secretions, cough, pneumonia), difficulty feeding, and weight loss. Six patients had documented reflux via diagnostic testing preoperatively. Five patients were on noninvasive positive pressure ventilation and other supportive respiratory therapies prior to surgery. All 7 patients survived the procedures. By August 2006, 5 patients with type I and 1 with severe type II spinal muscular atrophy were alive and medically stable at home 1.5 months to 41 months post-op. One patient with type I expired approximately 5 months post-op due to obstructive apnea. This case series demonstrates that laparoscopic gastrostomy tube placement coupled with Nissen fundoplication and noninvasive positive pressure ventilation can be successfully used as a treatment option to allow for early postoperative extubation and to optimize quality of life in type I and severe type II spinal muscular atrophy patients.
Flexural Vibration Control of the Circular Handlebars of a Bicycle by Using MFC Actuators
Authors: Ro Jeng-Jong , Chien Chin-Chie , Wei Teng-Yu , Sun Shuh-Jang
Published: July 2007

The newly developed Macro Fiber Composite (MFC) actuators are more flexible and conformable than traditional monolithic isotropic piezoceramic actuators, and capable of being surface-bonded in curved structures. In this study, both analytical prediction and experimental investigation are implemented to evaluate the effectiveness of active control of flexural vibration of the handlebars of a bicycle by using MFC actuators. The handlebars are simulated as a cantilevered hollow cylindrical rod surface-bonded with three flexible MFC actuators, two placed at the clamped end and the third at the bent location subjected to flexural vibration transmitted from a head tube. A finite element model and a Euler Bernoulli beam model are utilized to obtain the analytical predictions of natural frequencies and mode shapes of the MFC/handlebars. In the experimental verification, a primary disturbance is assumed to be transmitted from the clamped end, and a secondary force from the MFC actuators. Velocity feedback and a Linear Quadratic Regular (LQR) controller are utilized to determine appropriate voltage input into the MFC actuators. Close agreement is found between the theoretical assumptions and the experiments. The results obtained suggest that using the MFC actuators to control the flexural vibration of the MFC/handlebars of the bicycle is effective.
Supermarkets and imperial knowledge
Authors: Freidberg Susanne
Published: July 2007

Supermarkets employ codes of standards to assure the uniform safety, quality and `ethical' content of their food products. These standards represent a form of epistemic knowledge, intended to override the kinds of practical, local knowledge long employed in food production and trade. This form of food governance by standards bears a striking resemblance to other forms of imperial governance. This article explores the historical parallels and inherent contradictions of supermarket rule.
Arf6 recruits the Rac GEF Kalirin to the plasma membrane facilitating Rac activation
Authors: Koo Tae Hyeon , Eipper Betty A , Donaldson Julie G
Published: July 2007

Background

Many studies implicate Arf6 activity in Rac-mediated membrane ruffling and cytoskeletal reorganization. Although Arf6 facilitates the trafficking of Rac1 to the plasma membrane and in many cases Arf6 activation leads to the activation of Rac1, the details of how Arf6 influences Rac function remain to be elucidated.

Results

We demonstrate in binding assays and by co-immunoprecipitation that GDP-bound Arf6 binds to Kalirin5, a Rho family guanine nucleotide exchange factor, through interaction with the spectrin repeat region. In cells, expression of wild type Arf6 recruits spectrin repeat 5 and Kalirin to the plasma membrane and leads to enhanced Kalirin5-induced ruffling. By contrast, expression of an Arf6 mutant that cannot become activated, Arf6 T27N, still recruits spectrin repeat 5 and Kalirin to membranes but inhibits Kalirin5-induced ruffling in HeLa cells. Kalirin5-induced Rac1 activation is increased by the expression of wild type Arf6 and decreased by Arf6T27N. Furthermore, expression of a catalytically-inactive mutant of Kalirin5 inhibits cytoskeletal changes observed in cells expressing EFA6, an Arf6 guanine nucleotide exchange factor that leads to activation of Rac.

Conclusion

We show here with over-expressed proteins that the GDP-bound form of Arf6 can bind to the spectrin repeat regions in Kalirin Rho family GEFs thereby recruiting Kalirin to membranes. Although Kalirin is recruited onto membranes by Arf6-GDP, subsequent Rac activation and membrane ruffling requires Arf6 activation. From these results, we suggest that Arf6 can regulate through its GTPase cycle the activation of Rac.
siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake
Authors: Galvez Thierry , Teruel Mary N , Heo Won Do , Jones Joshua T , Kim Man Lyang , Liou Jen , Myers Jason W , Meyer Tobias
Published: July 2007

Background

Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth, viability and proliferation in tumor cells as well as non-transformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not yet been identified.

Results

We surveyed the human signaling proteome for regulators that increase or decrease transferrin uptake by screening 1,804 dicer-generated signaling small interfering RNAs using automated quantitative imaging. In addition to known transport proteins, we identified 11 signaling proteins that included a striking signature set for the phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3)-target of rapamycin (mTOR) signaling pathway. We show that the PI3K-mTOR signaling pathway is a positive regulator of transferrin uptake that increases the number of transferrin receptors per endocytic vesicle without affecting endocytosis or recycling rates.

Conclusion

Our study identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake and serves as a proof-of-concept that targeted RNA interference screens of the signaling proteome provide a powerful and unbiased approach to discover or rank signaling pathways that regulate a particular cell function.
Telomere Length in Human Natural Killer Cell Subsets
Authors: OUYANG QIN , BAERLOCHER GABRIELA , VULTO IRMA , LANSDORP PETER M.
Published: July 2007

Abstract:  Natural killer (NK) cells are cytotoxic cells that play a critical role in the innate immune response against infections and tumors. In the elderly, the cytotoxic function of NK cells is often compromised. Telomeres progressively shorten with each cell division and with age in most somatic cells eventually leading to chromosomal instability and cellular senescence. We studied the telomere length in NK cell subsets isolated from peripheral blood using “flow FISH,” a method in which the hybridization of telomere probe in cells of interest is measured relative to internal controls in the same tube. We found that the average telomere length in human NK cells decreased with age as was previously found for human T lymphocytes. Separation of adult NK cells based on CD56 and CD16 expression revealed that the telomere length was significantly shorter in CD56dimCD16+ (mature) NK cells compared to CD56brightCD16− (immature) NK cells from the same donor. Furthermore, sorting of NK cells based on expression of activation markers, such as NKG2D and LFA‐1, revealed that NK cells expressing these markers have significantly shorter telomeres. Telomere fluorescence was very heterogeneous in NK cells expressing CD94, killer inhibitory receptor (KIR), NKG2A, or CD161. Our observations indicate that telomeric DNA in NK cells is lost with cell division and with age similar to what has been observed for most other hematopoietic cells. Telomere attrition in NK cells is a plausible cause for diminished NK cell function in the elderly.
Insertional Mutagenesis by Replication‐Deficient Retroviral Vectors Encoding the Large T Oncogene
Authors: LI ZHIXIONG , KUSTIKOVA OLGA S. , KAMINO KENJI , NEUMANN THOMAS , RHEIN MATHIAS , GRASSMAN ELKE , FEHSE BORIS , BAUM CHRISTOPHER
Published: July 2007

Abstract:  Insertion sites of replication‐deficient retroviral vectors may trigger clonal dominance of hematopoietic cells in vivo. Here, we tested whether this would also be the case when using vectors that express powerful oncogenes, such as the large tumor antigen (TAg) of simian virus 40. TAg inactivates the tumor‐suppressor proteins p53 and Rb by virtue of a chaperone‐like activity. Primary hematopoietic stem/progenitor cells transduced with retroviral vectors encoding TAg‐induced histiocytic sarcoma (HS) or myeloid leukemia (ML) in transplanted mice (average survival of 21 weeks). Retrovirally introducing TAg into pretransformed 32D cells generated a monocytic leukemia, with faster kinetics (∼8 weeks). Leukemic clones showed retroviral insertions in genes contributing to all known TAg cooperation pathways, acting mitogenic and/or modulating apoptosis (such as BclX, Crk, Pim2, Csfr1/Pdgfrb, Osm/Lif, Axl, Fli, Sema4b, Sox4). 32D‐derived monocytic leukemias showed hits in Pim2 and Max proto‐oncogenes, or the chaperone Hspa4, plus additional signaling genes. Vector‐mediated insertional mutagenesis thus revealed a broad spectrum of potential TAg complementation genes. These findings have important implications for the use of retroviral transgenesis in cancer research, and the expression of signaling genes in somatic gene therapy.
Thrombopoietic Cells and the Bone Marrow Vascular Niche
Authors: KOPP H. G. , RAFII S.
Published: July 2007

Abstract:  Megakaryocytes and platelets have been known to secrete angiogenic growth factors for a long time. However, there is little in vivo data on the regulation of angiogenesis by thrombopoietic cells. Both megakaryocytes and platelets are known to carry and release a multitude of both pro‐ and antiangiogenic mediators. Thus, it remained unknown how the “angiogenic phenotype” of thrombopoietic cells would be determined. Our group established that platelets contribute to angiogenesis as carriers of SDF‐1, which is released by platelets in response to stimulation with hematopoietic cytokines. Indeed, even the action of VEGF‐A seems to be mediated in part by the release of SDF‐1 from stimulated platelets, thereby attracting proangiogenic hematopoietic cells. Moreover, the analysis of murine plasma and serum showed that similar to VEGF‐A, SDF‐1 is almost exclusively derived from platelets, and only trace amounts are detectable in platelet poor plasma. Because tumor patients' platelets have been shown to contain lower amounts of thrombospondin (Tsp), we generated Tsp‐1 and Tsp‐2 double knockout mice by crossing the single knockout lines. Interestingly, megakaryocytes and platelets derived from these mice confer a proangiogenic phenotype both in the bone marrow and in reperfusion of ischemic hindlimbs, thereby verifying the hypothesis of pro‐ and antiangiogenic platelet constituents “in balance.”
Epigenetic Control of Hematopoietic Stem Cell Aging The Case of Ezh2
Authors: De HAAN GERALD , GERRITS ALICE
Published: July 2007

Abstract:  Hematopoietic stem cells have potent, but not unlimited, selfrenewal potential. The mechanisms that restrict selfrenewal are likely to play a role during aging. Recent data suggest that the regulation of histone modifications by Polycomb group genes may be of crucial relevance to balance selfrenewal and aging. We provide evidence for the involvement of one of these Polycomb group genes, Ezh2, in aging of the hematopoietic stem cell system.
The Stem Cell Continuum
Authors: QUESENBERRY PETER J. , COLVIN GERALD , DOONER GERRI , DOONER MARK , ALIOTTA JASON M. , JOHNSON KEVIN
Published: July 2007

Abstract:  The phenotype of the hematopoietic stem cell is intrinsically labile and impacted by cell cycle and the effects of tissue injury. In published studies we have shown that there are changes in short‐ and long‐term engraftment, progenitor numbers, gene expression, and differentiation potential with cytokine‐induced cell cycle transit. Critical points here are that these changes are reversible and not unidirectional weighing, heavily against a hierarchical model of stem cell regulation. Furthermore, a number of studies have now established that stem cells separated by lineage depletion and selection for Sca‐1 or c‐kit or low rhodamine and Hoechst staining are in fact a cycling population. Last, studies on Hoechst separated “cycling” stem cells indicates that the observed phenotype shifts relate to phase of cell cycle and are not due to in vitro exposure to cytokines. These data suggest a continuum model of stem cell regulation and further indicate that this model holds for in vivo situations. Observations that marrow cells can convert to various tissue cells under different injury conditions continue to be published despite a small, but influential, number of negative studies. Our studies and those of others indicate that conversions of marrow‐derived cells to different tissue cells, such as skeletal muscle and lung, is critically dependent upon multiple variables, the most important of which is the presence of tissue injury. Variables which affect conversion of marrow cells to nonhematopoietic cells after in vivo transplantation include the nature and timing of the injury; marrow mobilization; the marrow cell type infused; the timing of cell infusion and the number of cells infused; the cell cycle state of the marrow cells, and other functional alterations in the marrow cells the treatment of the host mouse separate from specific injury; the mode of cell delivery; and possibly the presence of microvesicles from injured tissue. At least some of the highlighted negative reports on stem cell plasticity appear to be due to a failure to address these variables. Recently, we have observed that irradiated lung releases microvesicles which can enter marrow cells and lead to the marrow cells expressing lung‐specific mRNA and protein. This could provide an underlying mechanism for many of the plasticity phenomena. Altogether, marrow appears to represent a highly flexible ever‐changing cell system with the capacity to respond to products of injured cells and top repair a broad range of tissues.
Effect of FLT3 Inhibition on Normal Hematopoietic Progenitor Cells
Authors: WEISEL KATJA C. , YILDIRIM SEDAT , SCHWEIKLE ERIC , KANZ LOTHAR , MÖHLE ROBERT
Published: July 2007

Abstract:  Ligand‐mediated activation of the FMS‐like tyrosine kinase‐3 (FLT3) receptor is important for normal proliferation of primitive hematopoietic cells. FLT3 expression in the bone marrow is restricted to CD34+ cells and a subset of dendritic precursors. FLT3, as a member of the type III RTK subfamily, is closely related to c‐kit, c‐FMS, and PDGFα/β and is an unspecific target of tyrosine kinase inhibitors, such as imatinib. Activating mutations of FLT3 play an important role in leukemogenesis and their presence is associated with poor prognosis in acute myeloid leukemia (AML). Targeting the mutation by inhibiting the tyrosine kinase activity of FLT3 is a promising therapeutic option in the treatment of AML patients. CEP‐701 (Lestaurtinib), an indocarbazole derivate, is an FLT3 tyrosine kinase inhibitor. In this study, we investigated the effect of FLT3 kinase inhibition on normal hematopoietic stem and progenitor cells in vitro. FLT3 inhibition in normal CD34+ cells resulted in a dose‐dependent inhibitory effect in cell expansion. In contrast, progenitor cell function remained nearly unaffected. Blocking the FLT3 ligand by a neutralizing antibody partially restored the effects of FLT3 inhibition. These findings might explain hematotoxicity of tyrosine kinase inhibitors such as imatinib.
Manderlay (2005): Lars von Trier's narrative of passing
Authors: Doughty Ruth
Published: July 2007

Von Trier, the maverick Danish director, has over the course of his career earned a reputation for being difficult; he has a tendency to create films that are not only challenging but demand an active level of participation from his audience. The film Manderlay (2005) continues
this tradition of provoking intellectual debate. Whereas numerous scholars and critics have recognised that the film can be read as a metaphorical reference to George W. Bush's invasion of Iraq, this article interprets Manderlay as an allegory for the way African Americans have been
represented by the US film industry.
Does nitric oxide act in the ventromedial preoptic area to mediate oestrogen negative feedback in the seasonally anoestrous ewe?
Authors: McManus Christina J , Valent Miroslav , Hardy Steven L , Goodman Robert L
Published: July 2007

Seasonal anoestrus in the ewe results from enhanced oestrogen negative feedback. Recent data have implicated the ventromedial preoptic area (vmPOA) as an important site of oestrogen action. This study addressed whether NO acts within the vmPOA to inhibit LH during seasonal anoestrus. In Experiment 1, microimplants containing Nω-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), S-methyl thiocitrulline (SMTC, neural NOS (nNOS) inhibitor) or empty implants (control) were administered during mid-anoestrus to the vmPOA. l-NAME, but not SMTC, significantly increased LH pulse frequency. For Experiment 2, ewes in late anoestrus were administered 7-nitroindazole (7NI; nNOS inhibitor), l-NAME, SMTC, or empty implants. 7NI, but not l-NAME or SMTC, increased LH pulse frequency. In Experiment 3, the effects of microimplants and microinjections of l-NAME were compared in mid-anoestrus. Microinjections of l-NAME (300 nl at 10 μg/μl) increased LH pulse frequency, but microimplants did not. In late anoestrus, similar microinjections were ineffective. Taken together, the results of Experiments 1–3 suggested that NO inhibition may be stronger during the middle than at the end of seasonal anoestrus. To test this hypothesis, ewes in Experiment 4 received microinjection of l-NAME or vehicle thrice during the non-breeding season; none of the treatments increased LH pulse frequency. These results indicate that NO plays a role in the vmPOA in suppressing LH secretion during seasonal anoestrus because NOS inhibitors were consistently stimulatory when LH pulse frequency was low. However, the inconsistent and modest effects of these inhibitors suggest that NO actions in this area cannot completely account for the effects of inhibitory photoperiod.
Mitochondrial differentiation and oxidative phosphorylation system capacity in rat embryo during placentation period
Authors: Alcolea M P , Colom B , Lladó I , García-Palmer F J , Gianotti M
Published: July 2007

Mitochondrial biogenesis and function are essential for proper embryo development; however, these processes have not been further studied during the placentation period, when important oxidative metabolism activation is taking place. Thus, the aim of the present study was to investigate the oxidative phosphorylation system (OXPHOS) enzymatic activities as well as the expression of genes involved in the coordinated regulation of both mitochondrial and nuclear genomes (peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factors 1 and 2, mitochondrial single-strand DNA-binding protein, mitochondrial transcription factor A), and mitochondrial function (cytochrome c oxidase subunit IV, cytochrome c oxidase subunit I and β-ATP phosphohydrolase) in rat embryo throughout the placentation period (gestational days 11, 12 and 13). Our results reflect that embryo mitochondria were enhancing their OXPHOS potential capacities, pointing out that embryo mitochondria become more differentiated during the placentation period. Besides, the current findings show that the mRNAs of the nuclear genes involved in mitochondrial biogenesis were downregulated, whereas their protein content together with the mitochondrial DNA expression were upregulated throughout the period studied. These data indicate that the molecular regulation of the mitochondrial differentiation process during placentation involves a post-transcriptional activation of the nuclear-encoded genes that would lead to an increase in both the nuclear- and mitochondrial-encoded proteins responsible for the mitochondrial biogenic process. As a result, embryo mitochondria would reach a more differentiated stage with a more efficient oxidative metabolism that would facilitate the important embryo growth during the second half of the pregnancy.
Bovine herpesvirus 4 is tropic for bovine endometrial cells and modulates endocrine function
Authors: Donofrio Gaetano , Herath Shan , Sartori Chiara , Cavirani Sandro , Flammini Cesidio Filippo , Sheldon Iain Martin
Published: July 2007

Bovine postpartum uterine disease, metritis, affects about 40% of animals and is widely considered to have a bacterial aetiology. Although the γ-herpesvirus bovine herpesvirus 4 (BoHV-4) has been isolated from several outbreaks of metritis or abortion, the role of viruses in endometrial pathology and the mechanisms of viral infection of uterine cells are often ignored. The objectives of the present study were to explore the interaction, tropism and outcomes of BoHV-4 challenge of endometrial stromal and epithelial cells. Endometrial stromal and epithelial cells were purified and infected with a recombinant BoHV-4 carrying an enhanced green fluorescent protein (EGFP) expression cassette to monitor the establishment of infection. BoHV-4 efficiently infected both stromal and epithelial cells, causing a strong non-apoptotic cytopathic effect, associated with robust viral replication. The crucial step for the BoHV-4 endometriotropism appeared to be after viral entry as there was enhanced transactivation of the BoHV-4 immediate early 2 gene promoter following transient transfection into the endometrial cells. Infection with BoHV-4 increased cyclooxygenase 2 protein expression and prostaglandin estradiol secretion in endometrial stromal cells, but not epithelial cells. Bovine macrophages are persistently infected with BoHV-4, and co-culture with endometrial stromal cells reactivated BoHV-4 replication in the persistently infected macrophages, suggesting a symbiotic relationship between the cells and virus. In conclusion, the present study provides evidence of cellular and molecular mechanisms, supporting the concept that BoHV-4 is a pathogen associated with uterine disease.
The mitogen-activated protein kinase pathway tonically inhibits both basal and IGF-I-stimulated IGF-binding protein-5 production in mammary epithelial cells
Authors: Fleming Jodie M , Brandimarto Jeffrey A , Cohick Wendie S
Published: July 2007

The IGF system plays a key role in mammary gland growth and development. Our lab previously reported that IGF-I primarily regulates IGF-binding protein (BP)-3 in bovine mammary epithelial cells (MEC) and IGFBP-5 in mammary fibroblasts (MF). Presently, we examined the signaling pathways used by IGF-I to elicit this distinct, cell-type specific regulation. The phosphatidylinositol-3 kinase pathway was required for IGF-I to increase IGFBP-3 and -5 in MF and IGFBP-3 in MEC. Surprisingly, inhibiting the mitogen-activated protein kinase (MAPK) pathway in MEC increased IGFBP-5 mRNA levels 2- to 4-fold under basal conditions and 8- to 12-fold in cells treated with IGF-I within 4 h. Similar patterns of IGFBP-3 and -5 regulation were observed in murine MEC. Cells treated with IGF-I in the presence of MAPK inhibitors secreted more IGFBP-5 protein into conditioned media relative to cells treated with IGF-I alone; however, IGFBP-5 protein was not detected in conditioned media of cells treated with only a MAPK inhibitor. The IGFBP-5 mRNA response to MAPK inhibitors was specific for MEC, as blocking MAPK activity decreased the ability of IGF-I to induce IGFBP-5 in MF. In addition, no other IGFBP was increased in either cell type when MAPK activity was inhibited. These increases in IGFBP-5 expression in response to inhibition of the MAPK pathway corresponded with the induction of apoptosis. In conclusion, we report the novel observation that the MAPK/extracellular signal regulated kinase (ERK) pathway specifically represses IGFBP-5 expression in MEC. The corresponding changes in apoptosis and IGFBP-5 expression support a role for this specific IGFBP in mammary gland involution.
The presence of two distinct prolactin receptors in seabream with different tissue distribution patterns, signal transduction pathways and regulation of gene expression by steroid hormones
Authors: Huang Xigui , Jiao Baowei , Fung Chun Kit , Zhang Yong , Ho Walter K K , Chan Chi Bun , Lin Haoran , Wang Deshou , Cheng Christopher H K
Published: July 2007

Two prolactin receptors (PRLRs) encoded by two different genes were identified in the fugu and zebrafish genomes but not in the genomes of other vertebrates. Subsequently, two cDNA sequences corresponding to two PRLRs were identified in black seabream and Nile tilapia. Phylogenetic analysis of PRLR sequences in various vertebrates indicated that the coexistence of two PRLRs in a single species is a unique phenomenon in teleosts. Both PRLRs in teleosts (the classical one named as PRLR1, the newly identified one as PRLR2) resemble the long-form mammalian PRLRs. However, despite their overall structural similarities, the two PRLR subtypes in fish share very low amino acid similarities (about 30%), mainly due to differences in the intracellular domain. In particular, the Box 2 region and some intracellular tyrosine residues are missing in PRLR2. Tissue distribution study by real-time PCR in black seabream (sb) revealed that both receptors (sbPRLR1 and sbPRLR2) are widely expressed in different tissues. In gill, the expression level of sbPRLR2 is much higher than that of sbPRLR1. In the intestine, the expression of sbPRLR1 is higher than that of sbPRLR2. The expression levels of both receptors are relatively low in most other tissues, with sbPRLR1 generally higher than sbPRLR2. The sbPRLR1 and sbPRLR2 were functionally expressed in cultured human embryonic kidney 293 cells. Both receptors can activate the β-casein and c-fos promoters; however, only sbPRLR1 but not sbPRLR2 can activate the Spi promoter upon receptor stimulation in a ligand-specific manner. These results indicate that both receptors share some common functions but are distinctly different from each other in mobilizing post-receptor events. When challenged with different steroid hormones, the two PRLRs exhibited very different gene expression patterns in the seabream kidney. The sbPRLR1 expression was up-regulated by estradiol and cortisol, whereas testosterone had no significant effect. For sbPRLR2, its expression was down-regulated by estradiol and testosterone, while cortisol exerted no significant effect. The 5′-flanking regions of the sbPRLR1 and sbPRLR2 genes were cloned and the promoter activities were studied in transfected GAKS cells in the absence or presence of different steroid hormones. The results of the promoter studies were in general agreement with the in vivo hormonal regulation of gene expression results. The sbPRLR1 gene promoter activity was activated by estradiol and cortisol, but not by testosterone. In contrast, the sbPRLR2 gene promoter activity was inhibited by estradiol, cortisol, and testosterone.
Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic β-cells
Authors: Diakogiannaki Eleftheria , Dhayal Shalinee , Childs Caroline E , Calder Philip C , Welters Hannah J , Morgan Noel G
Published: July 2007

Long-chain saturated and monounsaturated fatty acids differ in their propensity to induce β-cell death in vitro with palmitate (C16:0) being cytotoxic, whereas palmitoleate (C16:1n-7) is cytoprotective. We now show that this cytoprotective capacity extends to a poorly metabolised C16:1n-7 derivative, methyl-palmitoleate (0.25 mM palmitate alone: 92 ± 4% death after 18 h; palmitate plus 0.25 mM methyl-palmitoleate: 12 ± 2%; P < 0.001). Palmitoleate and its methylated derivative also acted as mitogens in cultured β-cells (5-bromo-2-deoxyuridine incorporation – control: 0.15 ± 0.01 units; 0.25 mM palmitoleate: 0.22 ± 0.01 units; P < 0.05). It has been proposed that alterations in neutral lipid synthesis (particularly triacylglycerol (TAG) formation) might mediate the differential responses to saturated and unsaturated fatty acids and we have examined this proposition. Palmitate and palmitoleate both promoted β-cell phospholipid remodelling and increased TAG formation (control: 0.9 ± 0.1 nmol TAG/106 cells; 0.25 mM palmitate: 1.55 ± 0.07; 0.25 mM palmitoleate: 1.4 ± 0.05; palmitate plus palmitoleate: 2.3 ± 0.1). By contrast, methyl-palmitoleate failed to influence TAG levels (0.25 mM methyl-palmitoleate alone: 0.95 ± 0.06 nmol TAG/106 cells; methyl-palmitoleate plus palmitate: 1.5 ± 0.05) or its fatty acid composition in β-cells exposed to palmitate. The results suggest that monounsaturated fatty acids can promote cell viability and mitogenesis by a mechanism that does not require their metabolism and is independent of alterations in TAG formation.