bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMO1 Negatively Regulates Reactive Oxygen Species Production From NADPH Oxidases
Authors: Pandey Deepesh , Chen Feng , Patel Anand , Wang Cong-Yi , Dimitropoulou Christiana , Patel Vijay S. , Rudic R. Daniel , Stepp David W. , Fulton David J. 
Published: April 2011

Objective—
Increased protein SUMOylation (small ubiquitin-related modifier [SUMO]) provides protection from cellular stress, including oxidative stress, but the mechanisms involved are incompletely understood. The NADPH oxidases (Nox) are a primary source of reactive oxygen species (ROS) and oxidative stress, and thus our goal was to determine whether SUMO regulates NADPH oxidase activity.

Methods and Results—
Increased expression of SUMO1 potently inhibited the activity of Nox1 to Nox5. In contrast, inhibition of endogenous SUMOylation with small interfering RNA to SUMO1 or ubiquitin conjugating enzyme 9 or with the inhibitor anacardic acid increased ROS production from human embryonic kidney-Nox5 cells, human vascular smooth muscle cells, and neutrophils. The suppression of ROS production was unique to SUMO1, and it required a C-terminal diglycine and the SUMO-specific conjugating enzyme ubiquitin conjugating enzyme 9. SUMO1 did not modify intracellular calcium or Nox5 phosphorylation but reduced ROS output in an isolated enzyme assay, suggesting direct effects of SUMOylation on enzyme activity. However, we could not detect the presence of SUMO1 conjugation on Nox5 using a variety of approaches. Moreover, the mutation of more than 17 predicted and conserved lysine residues on Nox5 did not alter the inhibitory actions of SUMO1.

Conclusion—
Together, these results suggest that SUMO is an important regulatory mechanism that indirectly represses the production of ROS to ameliorate cellular stress.
Endothelial Fate and Angiogenic Properties of Human CD34
+
Progenitor Cells in Zebrafish
Authors: Pozzoli Ombretta , Vella Pietro , Iaffaldano Grazia , Parente Valeria , Devanna Paolo , Lacovich Marta , Lamia Carla Lora , Fascio Umberto , Longoni Daniela , Cotelli Franco , Capogrossi Maurizio C. , Pesce Maurizio 
Published: April 2011

Objective—
The vascular competence of human-derived hematopoietic progenitors for postnatal vascularization is still poorly characterized. It is unclear whether, in the absence of ischemia, hematopoietic progenitors participate in neovascularization and whether they play a role in new blood vessel formation by incorporating into developing vessels or by a paracrine action.

Methods and Results—

In the present study, human cord blood–derived CD34
+
(hCD34
+
) cells were transplanted into pre- and postgastrulation zebrafish embryos and in an adult vascular regeneration model induced by caudal fin amputation. When injected before gastrulation, hCD34
+
cells cosegregated with the presumptive zebrafish hemangioblasts, characterized by
Scl
and
Gata2
expression, in the anterior and posterior lateral mesoderm and were involved in early development of the embryonic vasculature. These morphogenetic events occurred without apparent lineage reprogramming, as shown by CD45 expression. When transplanted postgastrulation, hCD34
+
cells were recruited into developing vessels, where they exhibited a potent paracrine proangiogenic action. Finally, hCD34
+
cells rescued vascular defects induced by
Vegf-c
in vivo targeting and enhanced vascular repair in the zebrafish fin amputation model.

Conclusion—
These results indicate an unexpected developmental ability of human-derived hematopoietic progenitors and support the hypothesis of an evolutionary conservation of molecular pathways involved in endothelial progenitor differentiation in vivo.
Atheroprotective Reverse Cholesterol Transport Pathway Is Defective in Familial Hypercholesterolemia
Authors: Bellanger Natacha , Orsoni Alexina , Julia Zélie , Fournier Natalie , Frisdal Eric , Duchene Emilie , Bruckert Eric , Carrie Alain , Bonnefont-Rousselot Dominique , Pirault John , Saint-Charles Flora , Chapman M. John , Lesnik Philippe , Le Goff Wilfried , Guerin Maryse 
Published: April 2011

Objective—
Low high-density lipoprotein (HDL) cholesterol levels are frequently observed in familial hypercholesterolemia (FH) and might be associated with functional alterations of HDL particles that may influence their efficaciousness in the reverse cholesterol transport pathway.

Methods and Results—

We evaluated key steps of the reverse cholesterol transport, ie, cellular free cholesterol efflux, cholesteryl ester transfer protein-mediated cholesteryl ester (CE) transfer from HDL to apolipoprotein B–containing lipoproteins, and hepatic HDL-CE uptake, in patients displaying FH (n=12) and in healthy normolipidemic control subjects (n=12). Large HDL2 particles isolated from FH patients displayed a reduced capacity to mediate free cholesterol efflux via both scavenger receptor-BI– and ABCG1–dependent pathways. A significant inverse relationship between scavenger receptor-BI–dependent HDL2 efflux capacity and carotid intima-media thickness (
r
=−0.473;
P
=0.0186), as well as between ABCG1-dependent HDL2 efflux capacity and carotid intima-media thickness (
r
=−0.485;
P
=0.0212), was detected. We also observed an elevated cholesteryl ester transfer protein-mediated CE transfer from HDL2 and HDL3 particles to low-density lipoprotein and a reduced capacity of HDL particles to deliver CEs to the liver.

Conclusion—
We demonstrated that the centripetal movement of cholesterol from peripheral tissues, including the vessel wall, to feces is defective in FH, thereby emphasizing its atherogenicity.
Validity and Reliability of the Barthel Index Administered by Telephone
Authors: Della Pietra Gian Luca , Savio Katia , Oddone Elodie , Reggiani Monica , Monaco Francesco , Leone Maurizio A. 
Published: April 2011

Background and Purpose—
We aimed to evaluate validity and reliability of the Barthel Index administered telephonically compared with face-to-face assessment in clinically stable patients with stroke.

Methods—
One hundred thirty-one patients were interviewed twice by 2 registered nurses with identical training. Half of the patients were randomized to receive the telephone interview followed by the face-to-face interview and half the contrary. The sequence of interviewers was randomized.

Results—

The median value of the Barthel Index score was 30 (first to third interquartile range, 15 to 80) by telephone and 35 (15 to 75) by face-to-face (
P
=0.29). The weighted κ was 0.90 (95% CI, 0.85 to 0.94); κ values ranged from 0.70 (0.58 to 0.82) for bowel control to 0.91 (0.83 to 0.99) for bathing.

Conclusions—
Telephone assessment of stroke disability with the Barthel Index is reliable in comparison to direct face-to-face assessment.
Wind Speed Changes of North Atlantic Tropical Cyclones Preceding Landfall
Authors: Yaukey Peter 
Published: April 2011

AbstractLandfalling tropical cyclones have been extensively researched, especially their degradation upon coming ashore and the hazardous weather they create along coastlines and farther inland. Many of the factors that weaken storms over land could begin to act when they are still at sea, yet prelandfall intensity change remains poorly documented. This study examined the consistency of prelandfall changes in tropical cyclone intensity throughout the North Atlantic Ocean from 1950 to present. On average, cyclones intensified by 3 m s−1 less in their final 12 h before landfall than in the 12 h preceding those, on both mainland shores and in the Greater Antilles, while smaller islands showed no such change. Contributions of increasing storm age and poleward movement to this reduction were negligible. Two possible contributing factors to declining intensification before landfall were examined. The presence of a spring–neap tidal pattern of ~2 m s−1 in the prelandfall decline is consistent with tidal mixing influencing ocean temperature on the continental shelf. The tendency for the decline to be greater at night suggested the possible influence of solar heating on tropical cyclones near shore.
On the Arctic Wintertime Climate in Global Climate Models
Authors: Svensson Gunilla , Karlsson Johannes 
Published: April 2011

Abstract
Energy fluxes important for determining the Arctic surface temperatures during winter in present-day simulations from the Coupled Model Intercomparison Project phase 3 (CMIP3) multimodel dataset are investigated. The model results are evaluated over different surfaces using satellite retrievals and ECMWF interim reanalysis (ERA-Interim). The wintertime turbulent heat fluxes vary substantially between models and different surfaces. The monthly median net turbulent heat flux (upward) is in the range 100–200 W m−2 and −15 to 15 W m−2 over open ocean and sea ice, respectively. The simulated net longwave radiative flux at the surface is biased high over both surfaces compared to observations but for different reasons. Over open ocean, most models overestimate the outgoing longwave flux while over sea ice it is rather the downwelling flux that is underestimated. Based on the downwelling longwave flux over sea ice, two categories of models are found. One group of models that shows reasonable downwelling longwave fluxes, compared with observations and ERA-Interim, is also associated with relatively high amounts of precipitable water as well as surface skin temperatures. This group also shows more uniform airmass properties over the Arctic region possibly as a result of more frequent events of warm-air intrusion from lower latitudes. The second group of models underestimates the downwelling longwave radiation and is associated with relatively low surface skin temperatures as well as low amounts of precipitable water. These models also exhibit a larger decrease in the moisture and temperature profiles northward in the Arctic region, which might be indicative of too stagnant conditions in these models.
On the Role of Eddies and Surface Forcing in the Heat Transport and Overturning Circulation in Marginal Seas
Authors: Spall Michael A. 
Published: April 2011

Abstract
The factors that determine the heat transport and overturning circulation in marginal seas subject to wind forcing and heat loss to the atmosphere are explored using a combination of a high-resolution ocean circulation model and a simple conceptual model. The study is motivated by the exchange between the subpolar North Atlantic Ocean and the Nordic Seas, a region that is of central importance to the oceanic thermohaline circulation. It is shown that mesoscale eddies formed in the marginal sea play a major role in determining the mean meridional heat transport and meridional overturning circulation across the sill. The balance between the oceanic eddy heat flux and atmospheric cooling, as characterized by a nondimensional number, is shown to be the primary factor in determining the properties of the exchange. Results from a series of eddy-resolving primitive equation model calculations for the meridional heat transport, overturning circulation, density of convective waters, and density of exported waters compare well with predictions from the conceptual model over a wide range of parameter space. Scaling and model results indicate that wind effects are small and the mean exchange is primarily buoyancy forced. These results imply that one must accurately resolve or parameterize eddy fluxes in order to properly represent the mean exchange between the North Atlantic and the Nordic Seas, and thus between the Nordic Seas and the atmosphere, in climate models.
Understanding the Sensitivity of Different Drought Metrics to the Drivers of Drought under Increased Atmospheric CO2
Authors: Burke Eleanor J. 
Published: April 2011

AbstractA perturbed physics Hadley Centre climate model ensemble was used to study changes in drought on doubling atmospheric CO2. The drought metrics analyzed were based on 1) precipitation anomalies, 2) soil moisture anomalies, and 3) the Palmer drought severity index (PDSI). Drought was assumed to occur 17% of the time under single CO2. On doubling CO2, in general, PDSI drought occurs more often than soil moisture drought, which occurs more often than precipitation drought. This paper explores the relative sensitivity of each drought metric to changes in the main drivers of drought, namely precipitation and available energy. Drought tends to increase when the mean precipitation decreases, the mean available energy increases, the standard deviation of precipitation increases, and the standard deviation of available energy decreases. Simple linear approximations show that the sensitivity of drought to changes in mean precipitation is similar for the three different metrics. However, the sensitivity of drought to changes in the mean available energy (which is projected to increase under increased atmospheric CO2) is highly dependent on metric: with PDSI drought the most sensitive, soil moisture less sensitive, and precipitation independent of available energy. Drought metrics are only slightly sensitive to changes in the variability of the drivers. An additional driver of drought is the response of plants to increased CO2. This process reduces evapotranspiration and increases soil moisture, and generally causes less soil moisture drought. In contrast, the associated increase in available energy generally causes an increase in PDSI drought. These differing sensitivities need to be taken into consideration when developing adaptation strategies.
Sensitivities of Simulated Convective Storms to Environmental CAPE
Authors: Kirkpatrick Cody , McCaul Eugene W. , Cohen Charles 
Published: April 2011

Abstract
A set of 225 idealized three-dimensional cloud-resolving simulations is used to explore convective storm behavior in environments with various values of CAPE (450, 800, 2000, and 3200 J kg−1). The simulations show that when CAPE = 2000 J kg−1 or greater, numerous combinations of other environmental parameters can support updrafts of at least 10 m s−1 throughout an entire 2-h simulation. At CAPE = 450 J kg−1, it is very difficult to obtain strong storms, although one case featuring a supercell is found. For CAPE = 800 J kg−1, mature storm updraft speeds correlate positively with strong low-level lapse rates and reduced precipitable water. In some cases, updrafts at this CAPE value can reach speeds that rival predictions of parcel theory, but such efficient conversion of CAPE to kinetic energy does not extend to all storms at CAPE = 800 J kg−1, nor to any storms in simulations at lower or higher CAPE. In simulations with CAPE = 2000 or 3200 J kg−1, the strongest time-averaged mature updrafts, while supercellular in character, feature generally less than 60% of the speeds expected from parcel theory, and even the strongest updraft found at CAPE = 450 J kg−1 fails to reach that relative strength. When CAPE = 2000 J kg−1 or more, updrafts benefit from enhanced shear, higher levels of free convection, and reduced precipitable water.
Strong low-level shear and a reduced height of the level of free convection correlate closely with low-level storm vertical vorticity when CAPE is at least 2000 J kg−1, consistent with previous findings. However, at CAPE = 800 J kg−1, low-level vorticity shares the same correlations with the environment as updraft strength. With respect to storm precipitation, in simulations initiated with only 30 mm of precipitable water (PW), all of the storms that last for an entire 2-h simulation tend to produce liquid precipitation at roughly similar rates, regardless of their CAPE. In environments where PW is increased to 60 mm, storms tend to produce the most rainfall at CAPE = 2000 J kg−1, with somewhat lesser rainfall rates at lower and higher CAPE. Nevertheless, over the simulation domain, the ground area that receives at least 10 mm of rainfall tends to increase as CAPE increases, owing to a greater number and size of precipitating updrafts in the domain.
Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma
Authors: Munari Fabio , Lonardi Silvia , Cassatella Marco A. , Doglioni Claudio , Cangi Maria Giulia , Amedei Amedeo , Facchetti Fabio , Eishi Yoshinobu , Rugge Massimo , Fassan Matteo , de Bernard Marina , D'Elios Mario M. , Vermi William 
Published: April 2011

Abstract
Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a preneoplastic condition of the mucosa associated lymphoid tissue (MALT), which may evolve to a B-cell lymphoma. While it is well established that the initial neoplastic proliferation of B cells is antigen-driven and dependent on the helper activity of HP-specific T cells, it needs to be elucidated which cytokine or soluble factor(s) promote B-cell activation and lymphomagenesis. Herein, we originally report that gastric MALT lymphoma express high levels of a proliferation inducing ligand (APRIL), a novel cytokine crucial in sustaining B-cell proliferation. By immunohistochemistry, we demonstrate that APRIL is produced almost exclusively by gastric lymphoma-infiltrating macrophages located in close proximity to neoplastic B cells. We also show that macrophages produce APRIL on direct stimulation with both HP and HP-specific T cells. Collectively, our results represent the first evidence for an involvement of APRIL in gastric MALT lymphoma development in HP-infected patients.
p90RSK2 is essential for FLT3-ITD– but dispensable for BCR-ABL–induced myeloid leukemia
Authors: Elf Shannon , Blevins Dean , Jin Lingtao , Chung Tae-Wook , Williams Ifor R. , Lee Benjamin H. , Lin Jian-Xin , Leonard Warren J. , Taunton Jack , Khoury Hanna J. , Kang Sumin 
Published: April 2011

Abstract
p90 ribosomal S6 kinase 2 (p90RSK2) is important in diverse cellular processes including gene expression, cell proliferation, and survival. We found that p90RSK2 is commonly activated in diverse leukemia cell lines expressing different leukemogenic tyrosine kinases, including BCR-ABL and FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD). Interestingly, in a murine BM transplantation (BMT) model, genetic deficiency of RSK2 did not affect the pathogenesis or disease progression of BCR-ABL–induced myeloproliferative neoplasm (PN). In contrast, FLT3-ITD induced a T-cell acute lymphoblastic leukemia in BMT mice receiving RSK2 knockout (KO) BM cells, phenotypically distinct from the myeloproliferative neoplasm induced by FLT3-ITD using wild-type BM cells. In consonance with these results, inhibition of RSK2 by an RSK inhibitor, fmk, did not effectively induce apoptosis in BCR-ABL–expressing murine Ba/F3 cells, human K562 cells or primary tissue samples from CML patients, whereas fmk treatment induced significant apoptotic cell death not only in FLT3-ITD–positive Ba/F3 cells, human Molm14 and Mv(4;11) leukemia cells, but also in primary tissue samples from AML patients. These results suggest that RSK2 is dispensable for BCR-ABL–induced myeloid leukemia, but may be required for pathogenesis and lineage determination in FLT3-ITD–induced hematopoietic transformation. RSK2 may thus represent an alternative therapeutic target in the treatment of FLT3-ITD–positive leukemia.
WEE1 inhibition sensitizes osteosarcoma to radiotherapy
Authors: PosthumaDeBoer Jantine , Würdinger Thomas , Graat Harm CA , van Beusechem Victor W , Helder Marco N , van Royen Barend J , Kaspers Gertjan JL 
Published: April 2011

AbstractBackgroundThe use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G2cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G2arrest and could sensitize OS cells to irradiation induced cell death.MethodsWEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot.ResultsWEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G2arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment.ConclusionWe show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G2checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.
Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial
Authors: Rodewald Katlehn , Rentrop Mirjam , Holt Daniel V , Roesch-Ely Daniela , Backenstraß Matthias , Funke Joachim , Weisbrod Matthias , Kaiser Stefan 
Published: April 2011

Abstract

Background
The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions.

Methods
Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome.

Results
Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity.

Conclusion
A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings.

Trial registration
ClinicalTrials.gov NCT00507988