bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage Colony Stimulating Factor-Induced Macrophage Differentiation Influences Myotube Elongation
Authors: Keeling Sara , Deashinta Nadia , Howard Katherine M. , Vigil Sara , Moonie Sheniz , Schneider Barbara St. Pierre 
Published: July 2011

Background: Unaccustomed exercise, high-intensity dynamic sports activities, or the resumption of normal weight-bearing after a period of disuse can induce skeletal muscle injury, which activates an inflammatory response followed by muscle regeneration. Specific subsets of macrophages are involved in muscle regeneration. But the exact role of macrophage differentiation during muscle regeneration remains to be elucidated. Objective: The objective of the study was to examine the effect of macrophage colony stimulating factor (M-CSF)-differentiated, lipopolysaccharides (LPS)-stimulated-macrophage-conditioned medium on muscle-cell proliferation, fusion, and elongation, which are key events during muscle regeneration and myogenesis. Method: Murine C2C12 myoblasts were cultured in conditioned medium obtained from PU5-1R macrophages that were (a) undifferentiated, unstimulated; (b) M-CSF-differentiated, unstimulated; (c) undifferentiated, LPS-stimulated; or (d) M-CSF-differentiated, LPS-stimulated. Myoblast proliferation ratio, nuclei number, and length were measured. Results: C2C12 cells cultured in conditioned medium from M-CSF-differentiated, LPS-stimulated macrophages had significantly more nuclei and greater length than cells cultured in conditioned medium from undifferentiated, LPS-stimulated macrophages. Dilution and denaturization of the M-CSF-differentiated, LPS-stimulated-macrophage medium prevented a marked increase in C2C12 nuclei number and length. However, the C2C12 myoblast proliferation ratio was significantly greater in conditioned medium from undifferentiated, LPS-stimulated macrophages than in conditioned medium from M-CSF-differentiated, LPS-stimulated macrophages. Conclusions: M-CSF-differentiated, LPS-stimulated macrophages may influence myogenesis and the early and terminal stages of muscle regeneration. This knowledge may aid in developing therapies that will directly expedite muscle repair and lead to faster rehabilitation and reduced rehabilitation costs.
Differential niche and Wnt requirements during acute myeloid leukemia progression
Authors: Lane Steven W. , Wang Yingzi J. , Lo Celso Cristina , Ragu Christine , Bullinger Lars , Sykes Stephen M. , Ferraro Francesca , Shterental Sebastian , Lin Charles P. , Gilliland D. Gary , Scadden David T. , Armstrong Scott A. , Williams David A. 
Published: July 2011

Abstract
Hematopoietic stem cells (HSCs) engage in complex bidirectional signals with the hematopoietic microenvironment (HM), and there is emerging evidence that leukemia stem cells (LSCs) may use similar interactions. Using a syngeneic retroviral model of MLL-AF9 induced acute myeloid leukemia (AML), we have identified 2 different stages of leukemia progression, propagated by “pre-LSCs” and established leukemia (LSCs) and compared the homing properties of these distinctive entities to that of normal HSCs. The homing and microlocalization of pre-LSCs was most similar to long-term HSCs and was dependent on cell-intrinsic Wnt signaling. In contrast, the homing of established LSCs was most similar to that of committed myeloid progenitors and distinct from HSCs. Although osteoblast-derived Dickkopf-1, a potent Wnt inhibitor known to impair HSC function, dramatically impaired normal HSC localization within the bone marrow, it did not affect pre-LSCs, LSC homing, or AML development. Mechanistically, cell-intrinsic Wnt activation was observed in human and murine AML samples, explaining the independence of MLL-AF9 LSCs from niche-derived Wnt signals. These data identify differential engagement of HM associated with leukemic progression and identify an LSC niche that is physically distinct and independent of the constraints of Wnt signaling that apply to normal HSCs.
CD38 and chronic lymphocytic leukemia: a decade later
Authors: Malavasi Fabio , Deaglio Silvia , Damle Rajendra , Cutrona Giovanna , Ferrarini Manlio , Chiorazzi Nicholas 
Published: July 2011

AbstractThis review highlights a decade of investigations into the role of CD38 in CLL. CD38 is accepted as a dependable marker of unfavorable prognosis and as an indicator of activation and proliferation of cells when tested. Leukemic clones with higher numbers of CD38+ cells are more responsive to BCR signaling and are characterized by enhanced migration. In vitro activation through CD38 drives CLL proliferation and chemotaxis via a signaling pathway that includes ZAP-70 and ERK1/2. Finally, CD38 is under a polymorphic transcriptional control after external signals. Consequently, CD38 appears to be a global molecular bridge to the environment, promoting survival/proliferation over apoptosis. Together, this evidence contributes to the current view of CLL as a chronic disease in which the host's microenvironment promotes leukemic cell growth and also controls the sequential acquisition and accumulation of genetic alterations. This view relies on the existence of a set of surface molecules, including CD38, which support proliferation and survival of B cells on their way to and after neoplastic transformation. The second decade of studies on CD38 in CLL will tell if the molecule is an effective target for antibody-mediated therapy in this currently incurable leukemia.
The Impact of Tariff Structure on Customer Retention, Usage, and Profitability of Access Services
Authors: Iyengar Raghuram , Jedidi Kamel , Essegaier Skander , Danaher Peter J. 
Published: July 2011

Past research in marketing and psychology suggests that pricing structure may influence consumers' perception of value. In the context of two commonly used pricing schemes, pay-per-use and two-part tariff, we evaluate the impact of pricing structure on consumer preferences for access services. To this end, we develop a utility-based model of consumer retention and usage of a new service. A notable feature of the model is its ability to capture the pricing structure effect and measure its impact on consumer retention, usage, and pricing policy.Using data from a pricing field experiment for a new telecommunication service, we find that consumers derive lower utility from consumption under a two-part tariff than pay-per-use pricing, resulting in lower retention of customers and lower usage of the service. Specifically, our demand analysis shows that a two-part tariff structure leads to an average decline of 10.5% in the annual retention rate and an average decrease of 38.7% in yearly usage relative to pay-per-use pricing after controlling for income effects. Despite the higher customer churn and lower usage, we find that the two-part tariff is still the profit-maximizing pricing structure. However, our results show that if firms ignore the pricing structure (or access fee) effect, then they would overcharge customers for the access fee and undercharge them for the per-minute price. Translated in terms of profitability, the failure to account for the access fee effect leads to a reduction of 11% in firm profit.
New Product Diffusion Decisions Under Supply Constraints
Authors: Shen Wenjing , Duenyas Izak , Kapuscinski Roman 
Published: July 2011

Two recent papers on managing new product diffusion decisions under production constraints reach somewhat contradictory conclusions. Ho et al. (Ho, T.-H., S. Savin, C. Terwiesch. 2002. Managing demand and sales dynamics in new product diffusion under supply constraint. Management Sci. 48(2) 187–206) show that it is never optimal to refuse to satisfy any customers when the firm has inventory of the product. On the other hand, in a very similar model, Kumar and Swaminathan (Kumar, S., J. M. Swaminathan. 2003. Diffusion of innovations under supply constraints. Oper. Res. 51(6) 866–879) show that production constraints may in fact lead a firm to reject customers' orders even when the firm has the inventory to satisfy them (to slow down new product diffusion). We provide a counterexample to the results of Ho et al. (2002) and show that in their and Kumar and Swaminathan's (2003) models, it may be optimal to deny customers a product in inventory. We provide a generalization of both models that includes the ability to dynamically price the product (and also allows capacity and production costs to vary over time). We show that the unintuitive but optimal behavior of denying customers products that are in inventory disappears when the firm can dynamically set prices. This paper was accepted by Candace A. Yano, operations and supply chain management.
Microarray Analysis of the Infrapatellar Fat Pad in Knee Osteoarthritis: Relationship with Joint Inflammation
Authors: GANDHI RAJIV , TAKAHASHI MARK , VIRTANEN CARL , SYED KHALID , DAVEY J. RODERICK , MAHOMED NIZAR N. 
Published: July 2011

Objective.To examine differences in genes involved in fat metabolism, energy homeostasis, adipogenesis, and inflammation between endstage and early-stage knee osteoarthritis (OA) infrapatellar fat pads (IFP).Methods.Twenty-nine endstage and 5 early-stage primary OA IFP were harvested at knee surgery. Total RNA was extracted, labeled, and hybridized to whole-genome expression arrays. Unsupervised analysis of all samples using principal components analysis or 2-way hierarchical clustering showed groupings based on tissue source and disease. Statistical testing identified sets of genes that displayed differences between the 2 fat types. Western blot analysis was performed for protein expression of an identified gene of interest.Results.The 29 IFP demonstrated an elevation in the expression of adipokines such as adiponectin and leptin. A statistically significant increased expression was seen for genes of adipogenesis, such as peroxisome proliferator-activated receptor-γ (PPAR-γ), diacylglycerol acyltransferase 2 (DGAT2), cluster of differentiation (CD36), and thyroid hormone responsive spot (THRSP) in the severe OA fat pads as compared to the controls. A subset of 5 patients in the endstage OA group were consistently similar in gene expression to early OA tissue. Protein expression of PPAR-γ2 was 5.4-fold and PPAR-γ1 was 1.4-fold greater in endstage versus early OA tissue.Conclusion.Endstage OA fat pads demonstrated a significant upregulation of genes for fat metabolism and energy homeostasis and a mixed result for inflammatory cytokines.
The Longitudinal Outcome of Fibromyalgia: A Study of 1555 Patients
Authors: WALITT BRIAN , FITZCHARLES MARY-ANN , HASSETT AFTON L. , KATZ ROBERT S. , HÄUSER WINFRIED , WOLFE FREDERICK 
Published: July 2011

Objective.To describe the diagnosis status and outcome of patients diagnosed with fibromyalgia (FM) by US rheumatologists.Methods.We assessed 1555 patients with FM with detailed outcome questionnaires during 11,006 semiannual observations for up to 11 years. At entry, all patients satisfied American College of Rheumatology preliminary 2010 FM criteria modified for survey research. We determined diagnosis status, rates of improvement, responder subgroups, and standardized mean differences (effect sizes) between start and study completion scores of global well-being, pain, sleep problems, and health related quality of life. (QOL)Results.The 5-year improvement rates were pain 0.4 (95% CI 0.2, 0.5), fatigue 0.4 (95% CI 0.2, 0.05), and global 0.0 (95% CI −0.1, 0.1). The standardized mean differences were patient global 0.03 (95% CI −0.02, 0.08), pain 0.22 (95% CI 0.16, 0.28), sleep problems 0.20 (95% CI 0.14, 0.25), physical component summary of the Short-form 36 (SF-36) 0.11 (95% CI −0.14, −0.07), and SF-36 mental component summary 0.03 (95% CI −0.07, 0.02). Patients switched between criteria-positive and criteria-negative states, with 716 patients (44.0%) failing to meet criteria at least once during 4228.5 patient-years (7448 observations). About 10% of patients had substantial improvement and about 15% had moderate improvement of pain. Overall, FM severity worsened in 35.9% and pain in 38.6%.Conclusion.Although we found no average clinically meaningful improvement in symptom severity overall, 25% had at least moderate improvement of pain over time. The result that emerged from this longitudinal study was one of generally continuing high levels of self-reported symptoms and distress for most patients, but a slight trend toward improvement.
Uveitis-Associated Epitopes of Retinal Antigens Are Pathogenic in the Humanized Mouse Model of Uveitis and Identify Autoaggressive T Cells
Authors: Mattapallil Mary J. , Silver Phyllis B. , Mattapallil Joseph J. , Horai Reiko , Karabekian Zaruhi , McDowell J. Hugh , Chan Chi-Chao , James Eddie A. , Kwok William W. , Sen H. Nida , Nussenblatt Robert B. , David Chella S. , Caspi Rachel R. 
Published: July 2011

Abstract
Noninfectious uveitis is a leading cause of blindness and thought to involve autoimmune T cell responses to retinal proteins (e.g., retinal arrestin [soluble-Ag (S-Ag)]). There are no known biomarkers for the disease. Susceptibility is associated with HLA, but little is known about susceptible class II alleles or the potentially pathogenic epitopes that they present. Using a humanized HLA-transgenic mouse model of S-Ag–induced autoimmune uveitis, we identified several susceptible and resistant alleles of HLA-DR and -DQ genes and defined pathogenic epitopes of S-Ag presented by the susceptible alleles. The sequences of these epitopes overlap with some previously identified peptides of S-Ag (“M” and “N”), known to elicit memory responses in lymphocytes of uveitis patients. HLA-DR–restricted, S-Ag–specific CD4+ T cells could be detected in blood and draining lymph nodes of uveitic mice with HLA class II tetramers and transferred the disease to healthy mice. Importantly, tetramer-positive cells were detected in peripheral blood of a uveitis patient. To our knowledge, these findings provide the first tangible evidence that an autoimmune response to retina is causally involved in pathogenesis of human uveitis, demonstrating the feasibility of identifying and isolating retinal Ag-specific T cells from uveitis patients and may facilitate their development as biomarkers for the disease.
The Candida albicans GAP Gene Family Encodes Permeases Involved in General and Specific Amino Acid Uptake and Sensing
Authors: Kraidlova Lucie , Van Zeebroeck Griet , Van Dijck Patrick , Sychrová Hana 
Published: July 2011

ABSTRACT

The
Saccharomyces cerevisiae
general amino acid permease Gap1 (
Sc
Gap1) not only mediates the uptake of most amino acids but also functions as a receptor for the activation of protein kinase A (PKA). Fungal pathogens can colonize different niches in the host, each containing various levels of different amino acids and sugars. The
Candida albicans
genome contains six genes homologous to the
S. cerevisiae GAP1
. The expression of these six genes in
S. cerevisiae
showed that the products of all six
C. albicans
genes differ in their transport capacities.
C. albicans
Gap2 (
Ca
Gap2) is the true orthologue of
Sc
Gap1 as it transports all tested amino acids. The other
Ca
Gap proteins have narrower substrate specificities though
Ca
Gap1 and
Ca
Gap6 transport several structurally unrelated amino acids.
Ca
Gap1,
Ca
Gap2, and
Ca
Gap6 also function as sensors. Upon detecting some amino acids, e.g., methionine, they are involved in a rapid activation of trehalase, a downstream target of PKA. Our data show that
CaGAP
genes can be functionally expressed in
S. cerevisiae
and that
Ca
Gap permeases communicate to the intracellular signal transduction pathway similarly to
Sc
Gap1.
Identification of the Lipopolysaccharide Core of Yersinia pestis and Yersinia pseudotuberculosis as the Receptor for Bacteriophage φA1122
Authors: Kiljunen Saija , Datta Neeta , Dentovskaya Svetlana V. , Anisimov Andrey P. , Knirel Yuriy A. , Bengoechea José A. , Holst Otto , Skurnik Mikael 
Published: July 2011

ABSTRACT

φA1122 is a T7-related bacteriophage infecting most isolates of
Yersinia pestis
, the etiologic agent of plague, and used by the CDC in the identification of
Y. pestis
. φA1122 infects
Y. pestis
grown both at 20°C and at 37°C. Wild-type
Yersinia pseudotuberculosis
strains are also infected but only when grown at 37°C. Since
Y. pestis
expresses rough lipopolysaccharide (LPS) missing the O-polysaccharide (O-PS) and expression of
Y. pseudotuberculosis
O-PS is largely suppressed at temperatures above 30°C, it has been assumed that the phage receptor is rough LPS. We present here several lines of evidence to support this. First, a rough derivative of
Y. pseudotuberculosis
was also φA1122 sensitive when grown at 22°C. Second, periodate treatment of bacteria, but not proteinase K treatment, inhibited the phage binding. Third, spontaneous φA1122 receptor mutants of
Y. pestis
and rough
Y. pseudotuberculosis
could not be isolated, indicating that the receptor was essential for bacterial growth under the applied experimental conditions. Fourth, heterologous expression of the
Yersinia enterocolitica
O:3 LPS outer core hexasaccharide in both
Y. pestis
and rough
Y. pseudotuberculosis
effectively blocked the phage adsorption. Fifth, a gradual truncation of the core oligosaccharide into the Hep/Glc (
l
-
glycero
-
d
-
manno-
heptose/
d
-glucopyranose)-Kdo/Ko (3-deoxy-
d
-
manno
-oct-2-ulopyranosonic acid/
d
-
glycero
-
d
-
talo-
oct-2-ulopyranosonic acid) region in a series of LPS mutants was accompanied by a decrease in phage adsorption, and finally, a
waaA
mutant expressing only lipid A, i.e., also missing the Kdo/Ko region, was fully φA1122 resistant. Our data thus conclusively demonstrated that the φA1122 receptor is the Hep/Glc-Kdo/Ko region of the LPS core, a common structure in
Y. pestis
and
Y. pseudotuberculosis
.
Identification of the P3 Promoter and Distinct Roles of the Two Promoters of the SaeRS Two-Component System in Staphylococcus aureus
Authors: Jeong Do-Won , Cho Hoonsik , Lee Hyunwoo , Li Chunling , Garza Joshua , Fried Melinda , Bae Taeok 
Published: July 2011

ABSTRACT

In
Staphylococcus aureus
, the SaeRS two-component system (TCS) encoded by the
saePQRS
operon controls expression of major virulence factors, such as coagulase and alpha-hemolysin. The
saePQRS
operon has two promoters: P1 and P3. The P1 promoter, a strong promoter, is autoinduced and can transcribe all four genes. Compared with P1, P3 shows fairly low but constitutive promoter activity, and it transcribes only
saeR
and
saeS
, the two genes encoding response regulator SaeR and sensor kinase SaeS. However, the role of each promoter in
sae
signaling has not been rigorously defined. In this study, we found that the genuine transcription start site (TSS) of P3 is located 78 nucleotides downstream of the previously reported TSS. Subsequently, the P3 promoter sequence was identified and validated by mutagenesis analyses. Deletion of the
saePQ
region including the P1 promoter did not significantly alter the expression patterns of coagulase and alpha-hemolysin, two well-known
sae
target genes. Due to its L18P substitution in a transmembrane domain, SaeS in strain Newman has a constitutive kinase activity. Interestingly, the mutation also rendered the protein unstable, but the protein stability was restored by SaeQ, suggesting a possible SaeQ-SaeS interaction. Ironically, the same mutation seems to increase mRNA stability. SaeR appears to be stabilized by SaeS, possibly by a protein-protein interaction. Chromosomal mutation of P1 did not affect the expression pattern of coagulase and alpha-hemolysin. Based on these results, we conclude that transcription of
saeRS
from P3 is sufficient for target gene activation and that P1 is not involved in the activation.
The costs and benefits of working with one's spouse: A two‐sample examination of spousal support, work–family conflict, and emotional exhaustion in work‐linked relationships
Authors: Halbesleben Jonathon R. B. , Wheeler Anthony R. , Rossi Ana Maria 
Published: July 2011

SummaryAlthough the prevalence of employees working within the same workplace or occupation with their spouse has increased, relatively little research has examined their experiences. On the basis of the boundary and conservation of resources (COR) theories, we argue that higher levels of work–family role integration among work‐linked couples will lead to higher levels of spousal support resources and lower levels of work–family conflict. This will, in turn, lead to lower emotional exhaustion among employees in a work‐linked relationship. Among two samples of employees in a variety of occupations, we found that being in a work‐linked relationship was associated with both higher spousal instrumental support as well as different forms of work–family conflict. The interaction between spousal support and work–family conflict was associated with emotional exhaustion. We discuss the implications of these findings for boundary and COR theories in terms of movement of resources across work–family boundaries and resource relevance in the strain process. Copyright © 2011 John Wiley & Sons, Ltd.
Successful management of osteoradionecrotic precoccygeal defect with the free latissimus dorsi muscle flap: Case report and literature review
Authors: Lin Chin‐Ta , Chen Shyi‐Gen , Chen Tim‐Mo , Dai Niann‐Tzyy , FU Ju‐Peng , Chang Shun‐Chen 
Published: July 2011

AbstractPerineal wound complications following abdominoperineal resection (APR) are still frequent and most troublesome complications. We report the case of a 79‐year‐old male found to have the huge precoccygeal defect with infection after APR for rectal carcinoma. Before surgery, the patient received a complete course of chemoradiation therapy to treat for downgrade staging of the rectal malignancy. Extensive debridement of the perianal wound was performed for three times, followed by perianal reconstruction and packing and augmentation of the precoccygeal dead space with free latissimus dorsi (LD) muscle flap. Although persisted wound infection was still observed after reconstruction, the patient still led a good result after one time of further debridement and split‐thickness skin graft. We selected free LD muscle flap to fill and seal off the large pelvic dead space without the needs to change the jackknife position of the patient after debridement. To the best of our knowledge, this is the first case reported in the literature with the radiation‐associated perianal wound infection after APR reconstructed successfully by free LD muscle flap. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.
Isolation of Pure Phospholipid Fraction from Egg Yolk
Authors: Gładkowski Witold , Chojnacka Anna , Kiełbowicz Grzegorz , Trziszka Tadeusz , Wawrzeńczyk Czesław 
Published: July 2011

AbstractThe phospholipid (PL) fraction from egg yolk was isolated and purified. In the procedure applied (method 2) the egg yolk was extracted with ethanol, precipitated using acetone chilled to −20 °C and washed using acetone. The purity of the samples was checked by HPLC analysis using a Charged Aerosol Detector (CAD). The results were compared with those obtained for the phospholipid fraction isolated and purified by deoiling yolk before extraction and the precipitation of PL with acetone chilled to 4 °C (method 1). The use of acetone chilled to −20 °C to precipitate and wash the phospholipids yielded the phospholipid fraction with 100% purity (78.7 ± 0.2 of phosphatidylcholine and 21.3 ± 0.2 of phosphatidylethanolamine). When deoiling and the 4 °C purification process was used (method 1) 0.4 ± 0.1% cholesterol and some traces of triacylglycerols remained in the PL fraction.