bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations
Authors: Gourh Pravitt , Arnett Frank C , Assassi Shervin , Tan Filemon K , Huang Mei , Diekman Laura , Mayes Maureen D , Reveille John D , Agarwal Sandeep K 
Published: October 2009

Abstract
Introduction
Systemic sclerosis (SSc) (scleroderma) is a complex autoimmune disease that clinically manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACAs), anti-topoisomerase antibodies (ATAs), and anti-RNA polymerase III antibodies (ARAs) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. The current report sought to determine whether plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibody subsets.

Methods
Plasma from 444 SSc patients and 216 healthy controls was obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACAs, ATAs, ARAs, or none of the above (antibody-negative). Levels of 13 cytokines were determined using multiplex assays.

Results
Compared with females, healthy control males had higher plasma levels of IL-2 (P = 0.008), IL-5 (P = 0.01) and IL-8 (P = 0.01). In addition, in controls, IL-6 (P = 0.02) and IL-17 (P = 0.01) levels increased with advancing age. After adjusting for age and gender, SSc patients had higher circulating levels of TNFα (P < 0.0001), IL-6 (P < 0.0001), and IFNγ (P = 0.05) and lower IL-17 (P = 0.0005) and IL-23 (P = 0.014). Additional analyses demonstrated that disease duration also influenced these cytokine profiles. IL-6 was elevated in ATA-positive and ARA-positive patients, but not in ACA-positive patients. IL-8 was uniquely increased in the ATA-positive subset while both ATA-positive and ACA-positive subsets had elevated IFNγ and IL-10. IL-5 was only significantly increased in the ACA-positive subset. Lastly, patients with interstitial lung disease had elevated IL-6 and patients with pulmonary hypertension had elevated IL-6 and IL-13.

Conclusions
Plasma cytokine profiles differ in SSc patients based on the presence of SSc-associated autoantibodies. Plasma cytokine profiles in SSc patients may also be affected by disease duration and the pattern of internal organ involvement.
Hypertrophy is induced during the in vitrochondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer
Authors: Steinert Andre F , Proffen Benedikt , Kunz Manuela , Hendrich Christian , Ghivizzani Steven C , Nöth Ulrich , Rethwilm Axel , Eulert Jochen , Evans Christopher H 
Published: October 2009

Abstract
Introduction
The present study compares bone morphogenetic protein (BMP)-4 and BMP-2 gene transfer as agents of chondrogenesis and hypertrophy in human primary mesenchymal stem cells (MSCs) maintained as pellet cultures.

Methods
Adenoviral vectors carrying cDNA encoding human BMP-4 (Ad.BMP-4) were constructed by cre-lox combination and compared to previously generated adenoviral vectors for BMP-2 (Ad.BMP-2), green fluorescent protein (Ad.GFP), or firefly luciferase (Ad.Luc). Cultures of human bone-marrow derived MSCs were infected with 5 × 102 viral particles/cell of Ad.BMP-2, or Ad.BMP-4, seeded into aggregates and cultured for three weeks in a defined, serum-free medium. Untransduced cells or cultures transduced with marker genes served as controls. Expression of BMP-2 and BMP-4 was determined by ELISA, and aggregates were analyzed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy.

Results
Levels of BMP-2 and BMP-4 in the media were initially 30 to 60 ng/mL and declined thereafter. BMP-4 and BMP-2 genes were equipotent inducers of chondrogenesis in primary MSCs as judged by lacuna formation, strong staining for proteoglycans and collagen type II, increased levels of GAG synthesis, and expression of mRNAs associated with the chondrocyte phenotype. However, BMP-4 modified aggregates showed a lower tendency to progress towards hypertrophy, as judged by expression of alkaline phosphatase, annexin 5, immunohistochemical staining for type X collagen protein, and lacunar size.

Conclusions
BMP-2 and BMP-4 were equally effective in provoking chondrogenesis by primary human MSCs in pellet culture. However, chondrogenesis triggered by BMP-2 and BMP-4 gene transfer showed considerable evidence of hypertrophic differentiation, with, the cells resembling growth plate chondrocytes both morphologically and functionally. This suggests caution when using these candidate genes in cartilage repair.
Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis
Authors: Lorente Leonardo , Martín María M , Labarta Lorenzo , Díaz César , Solé-Violán Jordi , Blanquer José , Orbe Josune , Rodríguez José A , Jiménez Alejandro , Borreguero-León Juan M , Belmonte Felipe , Medina Juan C , LLimiñana Maria C , Ferrer-Agüero José M , Ferreres José , Mora María L , Lubillo Santiago , Sánchez Manuel , Barrios Ysamar , Sierra Antonio , Páramo José A 
Published: October 2009

Abstract
Introduction
Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis.

Methods
This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls.

Results
Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45).

Conclusions
The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.
Oxidative stress can alter the antigenicity of immunodominant peptides
Authors: Weiskopf Daniela , Schwanninger Angelika , Weinberger Birgit , Almanzar Giovanni , Parson Walther , Buus Soren , Lindner Herbert , Grubeck-Loebenstein Beatrix 
Published: October 2009

Abstract
Oxidative modification of the CMVpp65495–503 peptide influences binding to the T-cell receptor and results in lower proliferation and IFNγ production of CMV-specific CD8+ T cells.
APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65495–503 (NLVPMVATV) peptide. Such modifications of an antigenic peptide can affect MHC binding or TCR recognition. Using binding and dissociation assays, we demonstrate that oxidative modification of the CMVpp65495–503 peptide leads to a decreased binding of the pMHC complex to the TCR, whereas binding of the peptide to the MHC class I molecule is not impaired. Additionally, we show that CD8+ T cells have a decreased proliferation and IFN-γ production when stimulated with oxidized CMVpp65495–503 peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65495–503 and the CMVoxpp65495–503 peptides preferentially stimulate BV8 T cells. Sequencing of this dominant BV family reveals a highly conserved CDR3 amino acid motif, independent of the mode of stimulation, demonstrating the recruitment of the same T cell clonotypes. Our results suggest that oxidative modification of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions.
Macrophage differentiation of myeloid progenitor cells in response to M-CSF is regulated by the dual-specificity phosphatase DUSP5
Authors: Grasset Marie-France , Gobert-Gosse Stéphanie , Mouchiroud Guy , Bourette Roland P 
Published: October 2009

Abstract
ERK phosphatase DUSP5 is transiently induced by M-CSF and its expression increases proliferation and favors granulocytic versus macrophage differentiation in myeloid progenitor cells lines.
M-CSF regulates the production, survival, and function of monocytes and macrophages. The MAPKs ERK1/2 are key elements for signal integration downstream of the M-CSFR, and their sustained activation is essential for macrophage differentiation. In this study, we sought to isolate genes whose induction by M-CSF is dependent on persistent MAPK activation, thereby being possibly involved in the commitment of myeloid progenitors to macrophage differentiation. Following SSH between cDNA libraries from FD-Fms cells stimulated by M-CSF for 8 h in the presence or the absence of the MEK inhibitor U0126, we isolated DUSP5. DUSP5 expression is induced by M-CSF in various myeloid cells and acts as a specific negative-feedback regulator of ERK1/2. In FD-Fms cells that proliferate and differentiate toward macrophages in response to M-CSF, overexpression of DUSP5 increased M-CSF-dependent proliferation and strongly decreased differentiation. Similarly, overexpression of DUSP5 in the multipotent EGER-Fms cells not only significantly increased M-CSF-induced proliferation and prevented macrophage differentiation but also favored granulocytic differentiation. Altogether, experiments demonstrated that DUSP5 is implicated in M-CSF signaling and suggested that it may influence myeloid cell fate.
MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis
Authors: Khatwa Umakanth A , Kleibrink Bjoern E , Shapiro Steven D , Subramaniam Meera 
Published: October 2009

Abstract
MMP-8 promotes migration of polymorphonuclear cells through collagen-rich matrices and protection is seen in MMP-8−/− mice in a heterotopic airway transplant model of OB.
Increased levels of MMP-8 (neutrophil collagenase) have been reported in OB, but the biological role of MMP-8 in OB is not known. MMP-8 is an interstitial collagenase highly expressed by polymorphonuclear leukocytes, which are prominent in early OB. Here, we show that MMP-8 promotes migration of PMNs through the collagen-rich matrix in a mouse heterotopic airway transplant model of OB. Overall, MMP-8−/− mice had significantly fewer PMNs in the airway lumen 2 and 14 days post-transplantation, and the percentage of PMNs traversing the matrix to the lumen was decreased markedly in the MMP-8−/− compared with WT mice at 14 days. There were significantly more PMNs outside of the lumen in the ECM in the MMP-8−/− mice compared with WT mice. In vitro, significantly fewer MMP-8−/− PMNs migrated through 3D cross-linked collagen gels than WT PMNs. MMP inhibitor GM6001 was also able to impede migration of WT PMNs through collagen gels. The decreased migration was likely a result of pericollagenase activity of MMP-8, as WT PMNs expressing MMP-8 were not able to migrate effectively through collagen that was resistant to the collagenase. Protection from OB was seen in the MMP-8−/− mice, as the airway lumen had significantly less obliteration and collagen deposition, suggesting that MMP-8 plays an important role in the pathogenesis of OB.
The role of experience in flight behaviour ofDrosophila
Authors: Hesselberg Thomas , Lehmann Fritz-Olaf 
Published: October 2009

SUMMARYExperience plays a key role in the acquisition of complex motor skills in running and flight of many vertebrates. To evaluate the significance of previous experience for the efficiency of motor behaviour in an insect, we investigated the flight behaviour of the fruit fly Drosophila. We reared flies in chambers in which the animals could freely walk and extend their wings, but could not gain any flight experience. These naive animals were compared with control flies under both open- and closed-loop tethered flight conditions in a flight simulator as well as in a free-flight arena. The data suggest that the overall flight behaviour in Drosophila seems to be predetermined because both groups exhibited similar mean stroke amplitude and stroke frequency, similar open-loop responses to visual stimulation and the immediate ability to track visual objects under closed-loop feedback conditions. In short free flight bouts, peak saccadic turning rate, angular acceleration, peak horizontal speed and flight altitude were also similar in naive and control flies. However, we found significant changes in other key parameters in naive animals such as a reduction in mean horizontal speed(–23%) and subtle changes in mean turning rate (–48%). Naive flies produced 25% less yaw torque-equivalent stroke amplitudes than the controls in response to a visual stripe rotating in open loop around the tethered animal,potentially suggesting a flight-dependent adaptation of the visuo-motor gain in the control group. This change ceased after the animals experienced visual closed-loop feedback. During closed-loop flight conditions, naive flies had 53% larger differences in left and right stroke amplitude when fixating a visual object, thus steering control was less precise. We discuss two alternative hypotheses to explain our results: the `neuronal experience'hypothesis, suggesting that there are some elements of learning and fine-tuning involved during the first flight experiences in Drosophila and the `muscular exercise' hypothesis. Our experiments support the first hypothesis because maximum locomotor capacity seems not to be significantly impaired in the naive group. Although this study primarily confirms the genetic pre-disposition for flight in Drosophila,previous experience may apparently adjust locomotor fine control and aerial performance, although this effect seems to be small compared with vertebrates.
Cavitation in the embryonic tracheal system ofManduca sexta
Authors: Woods H. Arthur , Sprague Jonathan C. , Smith Jennifer N. 
Published: October 2009

SUMMARYInsect tracheae form during embryonic development and initially contain liquid, which impedes transport of oxygen and carbon dioxide. Only later do tracheae fill with gas and come to support high rates of gas flux. This liquid-to-gas transition is poorly understood. Using eggs of the sphingid moth Manduca sexta, we show that longitudinal tracheae in embryos fill with gas in less than 5 s, without invasion of external air, by a process of cavitation. Cavitation requires that tracheal liquids be under tension, and we propose two complementary processes for generating it. One likely, classical mechanism is tracheolar fluid absorption, first proposed by Wigglesworth. Our data support this mechanism in Manduca: after cavitation, liquids are progressively drawn out of finer tracheal branches. The second, previously unknown, mechanism is evaporative water loss across the eggshell, which leads both to declining egg volume and to a larger negative pressure potential of water. The pressure potential helps to drive rapid expansion of small bubbles nucleated near spiracles. Once bubbles are large enough to have displaced liquid across the diameter of a trachea, negative capillary pressure reinforces subsequent expansion of the bubble. Together with predictions from modern cavitation theory, our observations substantiate Wigglesworth's contention that gas filling is promoted by increasing hydrophobicity associated with tanning of the spiracles and major tracheal branches.
Daily and seasonal rhythms in the respiratory sensitivity of red-eared sliders (Trachemys scripta elegans)
Authors: Reyes Catalina , Milsom William K. 
Published: October 2009

SUMMARYThe purpose of the present study was to determine whether the daily and seasonal changes in ventilation and breathing pattern previously documented in red-eared sliders resulted solely from daily and seasonal oscillations in metabolism or also from changes in chemoreflex sensitivity. Turtles were exposed to natural environmental conditions over a one year period. In each season, oxygen consumption, ventilation and breathing pattern were measured continuously for 24 h while turtles were breathing air and for 24 h while they were breathing a hypoxic–hypercapnic gas mixture (H–H). We found that oxygen consumption was reduced equally during the day and night under H–H in all seasons except spring. Ventilation was stimulated by H–H but the magnitude of the response was always less at night. On average, it was also less in the winter and greater in the reproductive season. The data indicate that the day–night differences in ventilation and breathing pattern seen previously resulted from daily changes in chemoreflex sensitivity whereas the seasonal changes were strictly due to changes in metabolism. Regardless of mechanism, the changes resulted in longer apneas at night and in the winter at any given level of total ventilation,facilitating longer submergence at times of the day and year when turtles are most vulnerable.
Aphid watery saliva counteracts sieve-tube occlusion: a universal phenomenon?
Authors: Will Torsten , Kornemann Sarah R. , Furch Alexandra C. U. , Tjallingii W. Fred , van Bel Aart J. E. 
Published: October 2009

SUMMARY
Ca2+-binding proteins in the watery saliva of Megoura viciae counteract Ca2+-dependent occlusion of sieve plates in Vicia faba and so prevent the shut-down of food supply in response to stylet penetration. The question arises whether this interaction between aphid saliva and sieve-element proteins is a universal phenomenon as inferred by the coincidence between sieve-tube occlusion and salivation. For this purpose,leaf tips were burnt in a number of plant species from four different families to induce remote sieve-plate occlusion. Resultant sieve-plate occlusion in these plant species was counteracted by an abrupt switch of aphid behaviour. Each of the seven aphid species tested interrupted its feeding behaviour and started secreting watery saliva. The protein composition of watery saliva appeared strikingly different between aphid species with less than 50%overlap. Secretion of watery saliva seems to be a universal means to suppress sieve-plate occlusion, although the protein composition of watery saliva seems to diverge between species.
Characterization of a blood-meal-responsive proton-dependent amino acid transporter in the disease vector, Aedes aegypti
Authors: Evans Amy M. , Aimanova Karlygash G. , Gill Sarjeet S. 
Published: October 2009

SUMMARY
After anautogenous mosquitoes ingest the required blood meal, proteins in it are rapidly cleaved, yielding a large pool of amino acids. Transport of these amino acids into gut epithelial cells and their subsequent translocation into other tissues is critical for oogenesis and other physiological processes. We have identified a proton amino acid transporter (PAT) in Aedes aegypti (AaePAT1, AAEL007191) which facilitates this transport and is expressed in epithelial cell membranes of larval caecae and the adult midgut. AaePAT1 encodes a 475 amino acid protein showing high similarity to Anopheles gambiae AGAP009896, Culex pipiensCPIJ011438 and Drosophila melanogaster CG7888. When expressed in Xenopus oocytes the transport kinetics showed AaePAT1 is a low affinity transporter with low substrate specificity, having Km and Vmax values of about 7.2 mmol l–1 and 69 pmol oocyte–1min–1, respectively, for glutamine. A number of other amino acids are also transported by this PAT. In female adult midgut, AaePAT1 transcript levels were induced after ingestion of a blood meal.
Hovering of model insects: simulation by coupling equations of motion with Navier–Stokes equations
Authors: Wu Jiang Hao , Zhang Yan Lai , Sun Mao 
Published: October 2009

SUMMARYWhen an insect hovers, the centre of mass of its body oscillates around a point in the air and its body angle oscillates around a mean value, because of the periodically varying aerodynamic and inertial forces of the flapping wings. In the present paper, hover flight including body oscillations is simulated by coupling the equations of motion with the Navier–Stokes equations. The equations are solved numerically; periodical solutions representing the hover flight are obtained by the shooting method. Two model insects are considered, a dronefly and a hawkmoth; the former has relatively high wingbeat frequency (n) and small wing mass to body mass ratio,whilst the latter has relatively low wingbeat frequency and large wing mass to body mass ratio. The main results are as follows. (i) The body mainly has a horizontal oscillation; oscillation in the vertical direction is about 1/6 of that in the horizontal direction and oscillation in pitch angle is relatively small. (ii) For the hawkmoth, the peak-to-peak values of the horizontal velocity, displacement and pitch angle are 0.11U (U is the mean velocity at the radius of gyration of the wing), 0.22c=4 mm(c is the mean chord length) and 4 deg., respectively. For the dronefly, the corresponding values are 0.02U, 0.05c=0.15 mm and 0.3 deg., much smaller than those of the hawkmoth. (iii) The horizontal motion of the body decreases the relative velocity of the wings by a small amount. As a result, a larger angle of attack of the wing, and hence a larger drag to lift ratio or larger aerodynamic power, is required for hovering,compared with the case of neglecting body oscillations. For the hawkmoth, the angle of attack is about 3.5 deg. larger and the specific power about 9%larger than that in the case of neglecting the body oscillations; for the dronefly, the corresponding values are 0.7 deg. and 2%. (iv) The horizontal oscillation of the body consists of two parts; one (due to wing aerodynamic force) is proportional to 1/cn2 and the other (due to wing inertial force) is proportional to wing mass to body mass ratio. For many insects, the values of 1/cn2 and wing mass to body mass ratio are much smaller than those of the hawkmoth, and the effects of body oscillation would be rather small; thus it is reasonable to neglect the body oscillations in studying their aerodynamics.