bluuebunny/crossref_metadata_2025_split huggingface dataset:
The YvrI Alternative σ Factor Is Essential for Acid Stress Induction of Oxalate Decarboxylase in
Bacillus subtilis
Authors: MacLellan Shawn R. , Helmann John D. , Antelmann Haike 
Published: December 2008

ABSTRACT

YvrI is a recently identified alternative σ factor in
Bacillus subtilis
that requires the coactivator YvrHa to activate transcription. Previously, a strain engineered to overproduce YvrI was found to overproduce oxalate decarboxylase (OxdC), and further analysis identified three YvrI-activated promoters preceding the
yvrI-yvrHa
,
yvrJ
, and
oxdC-yvrL
operons. Independently, proteome analyses identified OxdC as a highly abundant, cell wall-associated protein that accumulated under acidic growth conditions. We show here that the accumulation of OxdC in the cell wall proteome under acidic growth conditions is absolutely dependent on YvrI and is correlated with enhanced transcription of both the
yvrI-yvrHa
and the
oxdC-yvrL
operons. Conversely, OxdC accumulates to a high level even under nonacidic growth conditions in cells lacking YvrL, a negative regulator of YvrI/YvrHa-dependent transcription. These results indicate that YvrI and its associated coregulators YvrHa and YvrL are required for the regulation of OxdC expression by acid stress. The high-level accumulation of OxdC depends, in part, on a strong
oxdC
promoter. A regulatory sequence with similarity to an upstream promoter element (UP) was identified upstream of the
oxdC
promoter and is required for high-level promoter activity. Conservation of the YvrI/YvrHa/YvrL regulatory system among related species allowed us to deduce an expanded consensus sequence for the compositionally unusual promoters recognized by this new σ factor.
The Moisture Mode in the Quasi-Equilibrium Tropical Circulation Model. Part II: Nonlinear Behavior on an Equatorial β Plane
Authors: Sugiyama Masahiro 
Published: December 2008

Abstract
Numerical calculations of a simplified quasi-equilibrium tropical circulation model (QTCM) on the equatorial β plane have been performed to explore the nonlinear regime of the moisture mode. Sensitivity tests have examined the effects of nonlinear advection and nonlinear wind-induced surface heat exchange (WISHE). Starting from a spatially homogeneous radiative–convective equilibrium with some background gustiness, the model develops quasi-stationary moisture modes, as expected from linear analysis. Upon nonlinear saturation due to thermodynamic limiting processes, a different regime emerges. A classical Gill model augmented with a prognostic humidity variable is found to be able to capture the nonlinear dynamics of the moisture mode; the time evolution solely resides in the humidity variable, and it is possible to understand its dynamics by examining the humidity budget. A scaling analysis shows that the approximation with a Gill model is valid for disturbances whose time scale is much longer than the damping time scale of equatorial waves. When nonlinear WISHE is included, a large-scale disturbance of wavenumber 1 grows and moves westward because evaporation is enhanced to the west of increased convection. Turning on nonlinear advection leads to disturbances of wavenumber 10 that translate eastward via advection of dry air by Rossby gyres. Combining nonlinear WISHE and nonlinear advection leads to gross moist instability and prohibits long-term numerical integration, which suggests that QTCM must be refined to fully describe the nonlinear dynamics of the moisture mode.
Atmospheric Moisture Transport Moderates Climatic Response to the Opening of Drake Passage
Authors: Sijp Willem P. , England Matthew H. 
Published: December 2008

Abstract
The absence of the Drake Passage (DP) gateway in coupled models generally leads to vigorous Antarctic bottom water (AABW) formation, Antarctic warming, and the absence of North Atlantic deep-water (NADW) formation. Here the authors show that this result depends critically on atmospheric moisture transport by midlatitude storms. The authors use coupled model simulations employing geometries different only at the location of DP to show that oceanic circulation similar to that of the present day is possible when DP is closed and atmospheric moisture transport values enhanced by Southern Ocean storm activity are used. In this case, no Antarctic warming occurs in conjunction with DP closure. The authors also find that the changes in poleward heat transport in response to the establishment of the Antarctic Circumpolar Current (ACC) are small. This result arises from enhanced atmospheric moisture transport at the midlatitudes of the Southern Hemisphere (SH), although the values used remain within a range appropriate to the present day. In contrast, homogeneous or (near) symmetric moisture diffusivity leads to strong SH sinking and the absence of a stable Northern Hemisphere (NH) overturning state, a feature familiar from previous studies. The authors’ results show that the formation of NADW, or its precursor, may have been possible before the opening of the DP at the Eocene/Oligocene boundary, and that its presence depends on an interplay between the existence of the DP gap and the hydrological cycle across the midlatitude storm tracks.
A New Moist Turbulence Parameterization in the Community Atmosphere Model
Authors: Bretherton Christopher S. , Park Sungsu 
Published: December 2008

Abstract
A new moist turbulence parameterization is presented and implemented in the Community Atmosphere Model (CAM). It is derived from Grenier and Bretherton but has been heavily modified to improve its numerical stability and efficiency with the long time steps used in climate models. A goal was to provide a more physically realistic treatment of marine stratocumulus-topped boundary layers than in the current CAM.
Key features of the scheme include use of moist-conserved variables, an explicit entrainment closure for convective layers, diagnosis of turbulent kinetic energy (TKE) for computation of turbulent diffusivities, an efficient new formulation of TKE transport as a relaxation to layer-mean TKE, and unified treatment of all turbulent layers in each atmospheric column.
The scheme is compared with the default turbulence parameterizations in the CAM using three single-column modeling cases, using both operational and high vertical and time resolution. Both schemes performed comparably well on the dry convective boundary layer case. For a stable boundary layer case, the default CAM overdeepens the boundary layer unless its free-tropospheric mixing length is greatly reduced, whereupon the new scheme and default CAM again both perform well at both tested resolutions. A nocturnal stratocumulus case was much better simulated by the new scheme than the default CAM, with much less resolution sensitivity. Global climate simulations with the new scheme in tandem with a new shallow cumulus parameterization are presented in a companion paper.
BLNK suppresses pre–B-cell leukemogenesis through inhibition of JAK3
Authors: Nakayama Joji , Yamamoto Mutsumi , Hayashi Katsuhiko , Satoh Hitoshi , Bundo Kenji , Kubo Masato , Goitsuka Ryo , Farrar Michael A. , Kitamura Daisuke 
Published: December 2008

AbstractPre–B-cell leukemia spontaneously develops in BLNK-deficient mice, and pre–B-cell acute lymphoblastic leukemia cells in children often lack BLNK protein expression, demonstrating that BLNK functions as a tumor suppressor. However, the mechanism by which BLNK suppresses pre–B-cell leukemia, as well as the identification of other genetic alterations that collaborate with BLNK deficiency to cause leukemogenesis, are still unknown. Here, we demonstrate that the JAK3/STAT5 signaling pathway is constitutively activated in pre-B leukemia cells derived from BLNK−/− mice, mostly due to autocrine production of IL-7. Inhibition of IL-7R signaling or JAK3/STAT5 activity resulted in the induction of p27kip1 expression and cell-cycle arrest, accompanied by apoptosis in the leukemia cells. Transgene-derived constitutively active STAT5 (STAT5b-CA) strongly synergized with the loss of BLNK to initiate leukemia in vivo. In the leukemia cells, exogenously expressed BLNK inhibited autocrine JAK3/STAT5 signaling, resulting in p27kip1 induction, cell-cycle arrest, and apoptosis. BLNK-inhibition of JAK3 was dependent on the binding of BLNK to JAK3. These data indicate that BLNK normally regulates IL-7–dependent proliferation and survival of pre–B cells through direct inhibition of JAK3. Thus, somatic loss of BLNK and concomitant mutations leading to constitutive activation of Jak/STAT5 pathway result in the generation of pre–B-cell leukemia.
Insulin resistance in pulmonary arterial hypertension
Authors: Zamanian R. T. , Hansmann G. , Snook S. , Lilienfeld D. , Rappaport K. M. , Reaven G. M. , Rabinovitch M. , Doyle R. L. 
Published: December 2008

Although obesity, dyslipidemia and insulin resistance (IR) are well known risk factors for systemic cardiovascular disease, their impact on pulmonary arterial hypertension (PAH) is unknown. The present authors’ previous studies indicate that IR may be a risk factor for PAH. The current study has investigated the prevalence of IR in PAH and explored its relationship with disease severity.Clinical data and fasting blood samples were evaluated in 81 nondiabetic PAH females. In total, 967 National Health and Nutrition Examination Surveys (NHANES) females served as controls. The fasting triglyceride to high-density lipoprotein cholesterol ratio was used as a surrogate of insulin sensitivity.While body mass index was similar in NHANESversusPAH females (28.6versus28.7 kg·m−2), PAH females were more likely to have IR (45.7versus21.5%) and less likely to be insulin sensitive (IS; 43.2versus57.8%). PAH females mostly (82.7%) had New York Heart Association (NYHA) class II and III symptoms. Aetiology, NYHA class, 6-min walk-distance and haemodynamics did not differ between IR and IS PAH groups. However, the presence of IR and a higher NYHA class was associated with poorer 6-months event-free survival (58versus79%).Insulin resistance appears to be more common in pulmonary arterial hypertension females than in the general population, and may be a novel risk factor or disease modifier that might impact on survival.
Desferrioxamine attenuates minor lung injury following surgical acute liver failure
Authors: Kostopanagiotou G. G. , Kalimeris K. A. , Arkadopoulos N. P. , Pafiti A. , Panagopoulos D. , Smyrniotis V. , Vlahakos D. , Routsi C. , Lekka M. E. , Nakos G. 
Published: December 2008

Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF.14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg·kg−1·h−1for the first 6 h post-operatively and 2.4 mg·kg−1·h−1until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis.DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A2activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA2, platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals.DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA2and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar–capillary membrane permeability and prevents alveolar space collapse.
Corticosteroids suppressin vitrotonsillar proliferation in children with obstructive sleep apnoea
Authors: Kheirandish-Gozal L. , Serpero L. D. , Dayyat E. , Kim J. , Goldman J. L. , Snow A. , Bhattacharjee R. , Gozal D. 
Published: December 2008

Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system.Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically diagnosed OSA were cultured in control medium (CO) or after stimulation with lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10−5–10−7 M), fluticasone (FLU; 10−5–10−14 M) and budesonide (BUD; 10−4–10−14 M). Proliferation and apoptosis were assessed, and supernatants were assayed for the cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8.STIM increased tonsillar and adenoidal proliferation compared with CO (1,976±133versus404±69 counts·min−1; n = 54). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU>BUD>DEX (n = 25 per group). Conversely, CS increased cellular apoptosis (n = 20 per group). Furthermore, TNF-α, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n = 48 per group).Whole tissue cell cultures of adenoids and tonsils provide a useful approach forin vitroassessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.
The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis
Authors: Govindaraju Vasanthi , Michoud Marie-Claire , Ferraro Pasquale , Arkinson Janine , Safka Katherine , Valderrama-Carvajal Hector , Martin James G 
Published: December 2008

AbstractBackgroundMany cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.MethodsExperiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2ndto 5thpassage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+]i), cell contraction, migration and proliferation.ResultsThe IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca2+release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC20) in CF than in control cells. In addition, MLC20expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.ConclusionASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.
Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer
Authors: Fruchon Séverine , Poupot Mary , Martinet Ludovic , Turrin Cédric-Olivier , Majoral Jean-Pierre , Fournié Jean-Jacques , Caminade Anne-Marie , Poupot Rémy 
Published: December 2008

AbstractThe monocyte-macrophage (MΦ) lineage can undergo different pathways of activation. The classical priming by IFN-γ, then triggering by LPS, conducts MΦ toward proinflammatory responses, whereas the alternative activation by IL-4, IL-10, IL-13, or glucocorticoids directs them toward an anti-inflammatory, immunosuppressive phenotype. Recently, we have shown that synthetic phosphorus-containing dendrimers activate human monocytes. Here, we analyzed the gene expression of monocytes activated by an acid azabisphosphonic-capped, phosphorus-containing dendrimer by comparison with untreated monocytes. We found that 78 genes were up-regulated, whereas 62 genes were down-regulated. Analysis of these genes directed the hypothesis of an alternative-like, anti-inflammatory activation of human monocytes. This was confirmed by quantitative RT-PCR and analysis of the surface expression of specific markers by flow cytometry. Functional experiments of inhibition of CD4+ T-lymphocyte proliferation in MLR indicated that dendrimer-activated monocytes (da-monocytes) have an immune-suppressive phenotype similar to the one induced by IL-4. Moreover, da-monocytes preferentially enhanced amplification of CD4+ T cells, producing IL-10, an immunosuppressive cytokine. Therefore, phosphorus-containing dendrimers appear as new nanobiotools promoting an anti-inflammatory and immunosuppressive activation of human monocytes and thus, prove to be good candidates for innovative, anti-inflammatory immunotherapies.
Aggressive Surgical Policies in a Retrospectively Reviewed Single-Institution Case Series of Retroperitoneal Soft Tissue Sarcoma Patients
Authors: Gronchi Alessandro , Lo Vullo Salvatore , Fiore Marco , Mussi Chiara , Stacchiotti Silvia , Collini Paola , Lozza Laura , Pennacchioli Elisabetta , Mariani Luigi , Casali Paolo Giovanni 
Published: December 2008

Purpose To explore whether the adoption of a systematic attempt to perform wider resections may lead to prognostic improvements in retroperitoneal soft tissue sarcoma (RSTS). Patients and Methods Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out. Results Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years. Conclusion In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.
Diabetic Patients Have an Increased Risk of Vertebral Fractures Independent of BMD or Diabetic Complications
Authors: Yamamoto Masahiro , Yamaguchi Toru , Yamauchi Mika , Kaji Hiroshi , Sugimoto Toshitsugu 
Published: December 2008

Abstract
Although patients with type 2 diabetes (T2DM) have an increased risk of hip fracture, risk of vertebral fracture (VF) and its association with BMD are still unclear. We examined Japanese T2DM patients (161 men &gt;50 yr and 137 postmenopausal women) and non-DM controls (76 and 622, respectively) by lateral spine radiography and DXA at the lumbar spine (L), femoral neck (FN), and radius (R). Logistic regression analysis adjusted for age, body mass index, and L-BMD showed that the presence of T2DM was an independent risk factor for prevalent VFs in women (OR = 1.86, p = 0.019) and men (OR = 4.73, p &lt; 0.001). BMD at any site, however, was not significantly associated with the presence of prevalent VFs in T2DM patients, in contrast to the significant association in controls (at least p = 0.010). Comparison of T2DM patients with and without VFs showed no significant differences in BMD values, bone markers, or diabetes status. Receiver operating characteristic analysis showed that the absolute L-, FN-, and R-BMD values for detecting prevalent VFs were higher in T2DM patients than controls, whereas their sensitivity and specificity were lower. T2DM patients may have an increased risk of VFs independent of BMD or diabetic complication status, suggesting that bone quality may define bone fragility in T2DM.
Sequential Treatment of Severe Postmenopausal Osteoporosis After Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS)
Authors: Eastell Richard , Nickelsen Thomas , Marin Fernando , Barker Clare , Hadji Peyman , Farrerons Jordi , Audran Maurice , Boonen Steven , Brixen Kim , Gomes Jose Melo , Obermayer-Pietsch Barbara , Avramidis Avraam , Sigurdsson Gunnar , Glüer Claus C 
Published: December 2008

Abstract
It is unclear which treatment should be given after stopping teriparatide therapy for severe osteoporosis. In a prospective, randomized, controlled, 2-yr study, we compared BMD effects and clinical safety of three follow-up treatments (anabolic with teriparatide, antiresorptive with raloxifene, or no active treatment) after 1 yr of teriparatide. Postmenopausal women with osteoporosis and a recent fragility fracture received open-label teriparatide (20 μg/d) for 12 mo before they were randomized (3:1:1) to continue teriparatide (n = 305), switch to raloxifene 60 mg/d (n = 100), or receive no active treatment for the second year (n = 102). All patients received calcium and vitamin D supplementation. Changes in areal BMD from baseline to 24 mo were analyzed using mixed-model repeated measures. Daily teriparatide treatment for 2 yr significantly increased spine BMD by 10.7%. Patients receiving raloxifene in year 2 had no further change in spine BMD from year 1 (change from baseline, 7.9%), whereas patients receiving no active treatment had a BMD decrease of 2.5% in year 2 (change from baseline, +3.8%). At the total hip, BMD increases from baseline at 2 yr were 2.5% with teriparatide, 2.3% with raloxifene, and 0.5% with no active treatment; the respective changes at the femoral neck were 3.5%, 3.1%, and 1.3%. The study had insufficient power to assess antifracture efficacy. In conclusion, BMD increases progressively over 2 yr of teriparatide therapy in women with severe osteoporosis. After discontinuation of teriparatide, raloxifene maintains spine BMD and increases hip BMD.