bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphic microsatellite loci for the sand pocket mouseChaetodipus arenarius, an endemic from the Baja California Peninsula
Authors: MUNGUIA‐VEGA A. , RODRIGUEZ‐ESTRELLA R. , NACHMAN M. , CULVER M. 
Published: November 2008

AbstractFifteen polymorphic microsatellite loci were isolated from an enriched genomic library of the sand pocket mouseChaetodipus arenarius. The mean number of alleles per locus was 11.53 (range five to 19) and the average observed heterozygosity was 0.764 (range 0.121 to 1.0). The markers will be used for detecting the impact of human‐induced habitat fragmentation on patterns of gene flow, genetic structure, and extinction risk. In addition, these markers will be useful across the genus because most of the loci cross‐amplified and were polymorphic in three other species ofChaetodipus.
Fully informative microsatellite markers for the tetraploid plant Eritrichium nanum (Boraginaceae)
Authors: WIRTH L. R. , GRAF R. , BRODBECK S. , REBER‐FUNK C. , HOLDEREGGER R. , LANDERGOTT U. 
Published: November 2008

AbstractWe characterized eight polymorphic, codominant nuclear microsatellite loci in the tetraploid plant Eritrichium nanum. The different allelic configurations occurring under tetrasomic inheritance were fully resolved at all loci. Two natural populations showed high observed heterozygosities, which were in agreement with Hardy–Weinberg expectations. There was no evidence of genetic linkage disequilibrium for any pair of loci. The results suggest that these microsatellite markers are useful for mating system and population genetic analyses in high‐alpine E. nanum.
Racial differences in bone density and fracture risk in the United States
Authors: WALKER Marcella D. , BILEZIKIAN John P. 
Published: November 2008

AbstractMany studies indicate racial differences in areal bone mineral density (aBMD). African‐Americans tend to have the greatest aBMD, followed by Caucasian, Hispanic and Native Americans. Asian Americans, on average, have the lowest aBMD. Differences in aBMD are attenuated when adjustments are made for bone size, weight and lifestyle factors. While many studies have focused on racial differences in bone density, it is important to consider fracture risk since it is the clinically meaningful outcome and is determined by many factors other than bone density. African‐ and Asian‐Americans have a relatively low risk of fracture compared to other groups, despite drastically different bone density, as measured by dual X‐ray absorptiometry (DXA). Factors that cannot be completely evaluated by DXA, such as bone size, volumetric density, bone microarchitecture and turnover may be important in explaining disparate fracture rates. Newer technologies such as central quantitative computed tomography (CT) and high‐resolution peripheral CT promise to contribute important knowledge in this regard. Despite recent advances, more fracture risk data is needed for non‐Caucasian groups to assist in the development of relevant screening and treatment guidelines.
Mapping translational research into individualized prognosis of fracture risk
Authors: NGUYEN Tuan V. 
Published: November 2008

AbstractThe assessment of fracture risk has until now been based on the measurement of bone mineral density (BMD) and/or a prior fracture. Individuals with BMD T‐scores < –2.5 (e.g. osteoporosis) or with prior fractures are indicated for treatment. However, recent data have suggested that 55% of women and 74% of men who sustained a fracture did not have osteoporosis. Therefore, the current strategy reduces a small number of fractures in the general population, and new thinking is required for that majority of individuals whose BMD measurements are at or near (both sides) the current threshold of osteoporosis. An individual's absolute risk of fracture can be estimated from the individual risk profile, which includes age, BMD, weight or body mass index, prior fracture, comorbidities, corticosteroid use, lifestyle factors, and falls. Therefore, risk assessment must simultaneously consider all risk factors to which the individual is exposed. A number of prognostic models and predictive nomograms have been developed to estimate an individual's absolute risk of fracture, but they have not been externally validated. Nevertheless, these prognostic models can be effective tools for individualizing short‐term and long‐term risks of fracture, which can help patient counseling and selecting appropriate patients for intervention to maximize the benefit of fracture reduction in the general population.
Trends in calcium and vitamin D usage among older people in nursing care facilities in Australia: still falling short of the guidelines
Authors: SÀNCHEZ RIERA Lídia , WILSON Nicholas M. , SAMBROOK Philip N. , KOK Cindy , CUMMING Robert G. , CAMERON Ian D. , CHEN Jian Sheng , SIMPSON Judy , MASON Rebecca S. , SEIBEL Markus J. , MARCH Lynn M. 
Published: November 2008

AbstractObjective:  To determine the impact of awareness‐raising strategies of calcium and vitamin D supplements in the active management of bone health of older people living in nursing care facilities in Australia.Design:  We compared data drawn from two prospective cohort studies that have evaluated falls and fractures in older people living in hostels (intermediate care facilities): the FREE study (conducted from 1996–2002, n = 1107) and the ongoing FREEDOM study (commenced in 2006, n = 1284 screened individuals). Both studies recruited older people living in a large number of nursing care facilities in northern Sydney (Australia).Results:  We found a small but significant increase in both calcium and vitamin D supplementation in the FREEDOM study participants compared to those in the FREE study. Calcium alone increased from 6.2% to 10.5% (P = 0.0002), vitamin D alone from 5.8% to 7.9% (P = 0.04) and the combined use of calcium and vitamin D increased from 1.6% to 11.9% (P < 0.0001).Conclusion:  There appears to be increasing awareness of the need for calcium and vitamin D supplementation in older people in nursing care facilities. However, given the high prevalence of osteoporosis and vitamin D deficiency among this population, the levels of supplementation achieved must still be considered suboptimal for treatment and prevention of osteoporosis and falls.
Validation of the English version of the quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) in Malaysia
Authors: LAI Pauline Siew Mei , CHUA Siew Siang , CHAN Siew Pheng , LOW Wah Yun 
Published: November 2008

AbstractBackground:  Osteoporotic fractures will soon become a common problem in Asian countries including Malaysia, as the growth in the elderly population will be more marked in this region. This leads to loss of independence and reduced quality of life (QOL). QOL is used as an outcome measure in clinical trials to focus the management of diseases on the patient rather than the disease. To date, no such instrument for measuring QOL of osteoporosis patients has been validated in Malaysia.Aim:  To investigate the reliability and validity of the English version of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) in Malaysia.Methods:  QUALEFFO was administered twice to postmenopausal osteoporotic women on alendronate. The patient group consisted of 46 women with back pain while the control group consisted of 42 women without back pain.Results:  High internal consistency was seen in all domains in the QUALEFFO with Cronbach α of 0.74–0.95 and 0.53–0.89 in the patient and control group, respectively. Factor analysis also showed that each domain consisted of one component except for the social domain. The test‐retest reliability showed high correlation coefficient in all domains (0.50–0.90, P < 0.001). Patients with back pain showed significantly worse QOL in the overall total QUALEFFO score compared to the control group (P < 0.0001).Conclusions:  The English version of QUALEFFO was found to be reliable and valid for the evaluation of patients with osteoporosis and who understand English in Malaysia. This study also indicates that patients with back pain have poorer QOL.
Role of the Ser-287-Asn Replacement in the Hydrolysis Spectrum Extension of AmpC β-Lactamases in
Escherichia coli
Authors: Mammeri Hedi , Galleni Moreno , Nordmann Patrice 
Published: November 2008

ABSTRACT

Two AmpC variants harboring the S287N substitution were obtained by mutagenesis from cephalosporinases representative of the phylogenetic groups A and B2 of
Escherichia coli
. Their biochemical characterization revealed that the S287N replacement led to an important increase in the catalytic efficiency toward extended-spectrum cephalosporins in the AmpC β-lactamase of group A only.
Nationwide Survey of CTX-M-Type Extended-Spectrum β-Lactamases among
Klebsiella pneumoniae
Isolates in Slovenian Hospitals
Authors: Meško Meglič K. , Koren S. , Palepou M. F. I. , Karisik E. , Livermore D. M. , Pike R. , Andlovic A. , Jeverica S. , Križan-Hergouth V. , Müller-Premru M. , Seme K. , Woodford N. 
Published: November 2008

ABSTRACT

Among 177 extended-spectrum β-lactamase-producing
Klebsiella pneumoniae
isolates collected from 11 Slovenian hospitals in 2005 and 2006, 60 (34%), from eight hospitals, harbored genes for CTX-M enzymes, with
bla
CTX-M-15
detected by sequencing. These 60 isolates comprised 11 pulsed-field gel electrophoresis-defined strains, with several clusters of closely related isolates. Plasmids encoding CTX-M-15 enzyme were highly transmissible.
Inactivation of KsgA, a 16S rRNA Methyltransferase, Causes Vigorous Emergence of Mutants with High-Level Kasugamycin Resistance
Authors: Ochi Kozo , Kim Ji-Yun , Tanaka Yukinori , Wang Guojun , Masuda Kenta , Nanamiya Hideaki , Okamoto Susumu , Tokuyama Shinji , Adachi Yoshikazu , Kawamura Fujio 
Published: November 2008

ABSTRACT

The methyltransferases RsmG and KsgA methylate the nucleotides G535 (RsmG) and A1518 and A1519 (KsgA) in 16S rRNA, and inactivation of the proteins by introducing mutations results in acquisition of low-level resistance to streptomycin and kasugamycin, respectively. In a
Bacillus subtilis
strain harboring a single
rrn
operon (
rrnO
), we found that spontaneous
ksgA
mutations conferring a modest level of resistance to kasugamycin occur at a high frequency of 10
−6
. More importantly, we also found that once cells acquire the
ksgA
mutations, they produce high-level kasugamycin resistance at an extraordinarily high frequency (100-fold greater frequency than that observed in the
ksgA

+

strain), a phenomenon previously reported for
rsmG
mutants. This was not the case for other antibiotic resistance mutations (Tsp
r
and Rif
r
), indicating that the high frequency of emergence of a mutation for high-level kasugamycin resistance in the genetic background of
ksgA
is not due simply to increased persistence of the
ksgA
strain. Comparative genome sequencing showed that a mutation in the
speD
gene encoding
S
-adenosylmethionine decarboxylase is responsible for the observed high-level kasugamycin resistance.
ksgA speD
double mutants showed a markedly reduced level of intracellular spermidine, underlying the mechanism of high-level resistance. A growth competition assay indicated that, unlike
rsmG
mutation, the
ksgA
mutation is disadvantageous for overall growth fitness. This study clarified the similarities and differences between
ksgA
mutation and
rsmG
mutation, both of which share a common characteristic—failure to methylate the bases of 16S rRNA. Coexistence of the
ksgA
mutation and the
rsmG
mutation allowed cell viability. We propose that the
ksgA
mutation, together with the
rsmG
mutation, may provide a novel clue to uncover a still-unknown mechanism of mutation and ribosomal function.
Relative Strengths of the Class 1 Integron Promoter Hybrid 2 and the Combinations of Strong and Hybrid 1 with an Active P2 Promoter
Authors: Papagiannitsis Costas C. , Tzouvelekis Leonidas S. , Miriagou Vivi 
Published: November 2008

ABSTRACT

The relative strengths of the uncommon promoters hybrid 2, hybrid 1 with an active P2 promoter (hybrid 1+P2), and strong+P2, which drive transcription of resistance genes in class 1 integrons, were evaluated using
bla
GES-1
as a reporter gene cassette. Hybrid 2 was stronger than hybrid 1. Coupling P2 with the strong promoter and with hybrid 1 caused a measurable increase in GES-1 expression.
Neutrophils Are Essential for Rapid Clearance ofEnterococcus faeciumin Mice
Authors: Leendertse Masja , Willems Rob J. L. , Giebelen Ida A. J. , Roelofs Joris J. T. H. , Bonten Marc J. M. , van der Poll Tom 
Published: November 2008

ABSTRACTA progressive increase in infections with multiresistantEnterococcus faeciumhas been reported, especially in cancer patients and neutropenic patients. Despite its increasing importance as a nosocomial pathogen, knowledge of the pathogenesis ofE. faeciuminfections is highly limited. In this study, we investigated the role of neutrophils during peritonitis with subsequent bacteremia caused byE. faecium. Therefore, we depleted neutrophils by intraperitoneal injections of monoclonal antibody RB6-8C5. Mice were followed for 5 days, and the enterococcal outgrowth and inflammatory response were compared between neutropenic mice and immunoglobulin G-injected control mice. Neutropenic mice demonstrated a severe delay in enterococcal clearance from all cultured organs (peritoneal fluid, blood, and lung and liver tissue). In particular, neutropenic mice remained bacteremic for up to 3 days, whereas all nonneutropenic mice had cleared the bacteria from circulation by 2 days. Furthermore, neutropenic mice displayed elevated peritoneal cytokine and chemokine levels 1 day after the infection and attracted fewer macrophages into the peritoneal cavity. In the circulation, a prolonged elevation of tumor necrosis factor alpha, interleukin-6, and the acute-phase proteins serum amyloid A and complement 3 were measured in neutropenic mice. In conclusion, attraction of neutrophils to the primary site ofE. faeciuminfection is important for a rapid clearance of this bacterium, thereby attenuating a systemic inflammatory response.
Characterization ofEntamoeba histolyticaIntermediate Subunit Lectin-Specific Human Monoclonal Antibodies Generated in Transgenic Mice Expressing Human Immunoglobulin Loci
Authors: Tachibana Hiroshi , Cheng Xun-Jia , Tsukamoto Hideo , Itoh Johbu 
Published: November 2008

ABSTRACTFour fully human monoclonal antibodies (MAbs) toEntamoeba histolyticaintermediate subunit lectin (Igl) were prepared in XenoMouse mice, which are transgenic mice expressing human immunoglobulin loci. Examination of the reactivities of these MAbs to recombinant Igl1 and Igl2 ofE. histolyticashowed that XEhI-20 {immunoglobulin G2(κ) [IgG2(κ)]} and XEhI-28 [IgG2(κ)] were specific to Igl1, XEhI-B5 [IgG2(κ)] was specific to Igl2, and XEhI-H2 [IgM(κ)] was reactive with both Igls. Gene analyses revealed that the VHand VLgerm lines were VH3-48 and L2 for XEhI-20, VH3-21 and L2 for XEhI-28, VH3-33 and B3 for XEhI-B5, and VH4-4 and A19 for XEhI-H2, respectively. Flow cytometry analyses showed that the epitopes recognized by all of these MAbs were located on the surfaces of living trophozoites. Confocal microscopy demonstrated that most Igl1 and Igl2 proteins were colocalized on the surface and in the cytoplasm, but different localization patterns in intracellular vacuoles were also present. The preincubation of trophozoites with XEhI-20, XEhI-B5, and XEhI-H2 caused significant inhibition of the adherence of trophozoites to Chinese hamster ovary cells, whereas preincubation with XEhI-28 did not do so. XEhI-20, XEhI-B5, and XEhI-H2 were injected intraperitoneally into hamsters 24 h prior to intrahepatic challenge withE. histolyticatrophozoites. One week later, the mean abscess size in groups injected with one of the three MAbs was significantly smaller than that in controls injected with polyclonal IgG or IgM isolated from healthy humans. These results demonstrate that human MAbs to Igls may be applicable for immunoprophylaxis of amebiasis.
The Potassium Transporter Trk and External Potassium Modulate
Salmonella enterica
Protein Secretion and Virulence
Authors: Su Jing , Gong Hao , Lai Jeff , Main Andrew , Lu Sangwei 
Published: November 2008

ABSTRACT

Potassium (K
+
) is the most abundant intracellular cation and is essential for many physiological functions of all living organisms; however, its role in the pathogenesis of human pathogens is not well understood. In this study, we characterized the functions of the bacterial Trk K
+
transport system and external K
+
in the pathogenesis of
Salmonella enterica
, a major food-borne bacterial pathogen. Here we report that Trk is important for
Salmonella
to invade and grow inside epithelial cells. It is also necessary for the full virulence of
Salmonella
in an animal infection model. Analysis of proteins of
Salmonella
indicated that Trk is involved in the expression and secretion of effector proteins of the type III secretion system (TTSS) encoded by
Salmonella
pathogenicity island 1 (SPI1) that were previously shown to be necessary for
Salmonella
invasion. In addition to the role of the Trk transporter in the pathogenesis of
Salmonella
, we discovered that external K
+
modulates the pathogenic properties of
Salmonella
by increasing the expression and secretion of effector proteins of the SPI1-encoded TTSS and by enhancing epithelial cell invasion. Our studies demonstrated that K
+
is actively involved in the pathogenesis of
Salmonella
and indicated that
Salmonella
may take advantage of the high K
+
content inside host cells and in the intestinal fluid during diarrhea to become more virulent.
Borrelia burgdorferi
Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen
Authors: Brissette Catherine A. , Haupt Katrin , Barthel Diana , Cooley Anne E. , Bowman Amy , Skerka Christina , Wallich Reinhard , Zipfel Peter F. , Kraiczy Peter , Stevenson Brian 
Published: November 2008

ABSTRACT

Host-derived plasmin plays a critical role in mammalian infection by
Borrelia burgdorferi
. The Lyme disease spirochete expresses several plasminogen-binding proteins. Bound plasminogen is converted to the serine protease plasmin and thereby may facilitate the bacterium's dissemination throughout the host by degrading extracellular matrix. In this work, we demonstrate plasminogen binding by three highly similar borrelial outer surface proteins, ErpP, ErpA, and ErpC, all of which are expressed during mammalian infection. Extensive characterization of ErpP demonstrated that this protein bound in a dose-dependent manner to lysine binding site I of plasminogen. Removal of three lysine residues from the carboxy terminus of ErpP significantly reduced binding of plasminogen, and the presence of a lysine analog, ε-aminocaproic acid, inhibited the ErpP-plasminogen interaction, thus strongly pointing to a primary role for lysine residues in plasminogen binding. Ionic interactions are not required in ErpP binding of plasminogen, as addition of excess NaCl or the polyanion heparin did not have any significant effect on binding. Plasminogen bound to ErpP could be converted to the active enzyme, plasmin. The three plasminogen-binding Erp proteins can also bind the host complement regulator factor H. Plasminogen and factor H bound simultaneously and did not compete for binding to ErpP, indicating separate binding sites for both host ligands and the ability of the borrelial surface proteins to bind both host proteins.
Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas
Authors: Yang Fan , Van Meter Timothy E. , Buettner Ralf , Hedvat Michael , Liang Wei , Kowolik Claudia M. , Mepani Nilesh , Mirosevich Janni , Nam Sangkil , Chen Mike Y. , Tye Gary , Kirschbaum Mark , Jove Richard 
Published: November 2008

Abstract
Medulloblastomas are the most frequent malignant brain tumors in children. Sorafenib (Nexavar, BAY43-9006), a multikinase inhibitor, blocks cell proliferation and induces apoptosis in a variety of tumor cells. Sorafenib inhibited proliferation and induced apoptosis in two established cell lines (Daoy and D283) and a primary culture (VC312) of human medulloblastomas. In addition, sorafenib inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) in both cell lines and primary tumor cells. The inhibition of phosphorylated STAT3 (Tyr705) occurs in a dose- and time-dependent manner. In contrast, AKT (protein kinase B) was only decreased in D283 and VC312 medulloblastoma cells and mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2) were not inhibited by sorafenib in these cells. Both D-type cyclins (D1, D2, and D3) and E-type cyclin were down-regulated by sorafenib. Also, expression of the antiapoptotic protein Mcl-1, a member of the Bcl-2 family, was decreased and correlated with apoptosis induced by sorafenib. Finally, sorafenib suppressed the growth of human medulloblastoma cells in a mouse xenograft model. Together, our data show that sorafenib blocks STAT3 signaling as well as expression of cell cycle and apoptosis regulatory proteins, associated with inhibition of cell proliferation and induction of apoptosis in medulloblastomas. These findings provide a rationale for treatment of pediatric medulloblastomas with sorafenib. [Mol Cancer Ther 2008;7(11):3519–26]
The flavonoid kaempferol sensitizes human glioma cells to TRAIL-mediated apoptosis by proteasomal degradation of survivin
Authors: Siegelin Markus D. , Reuss David E. , Habel Antje , Herold-Mende Christel , von Deimling Andreas 
Published: November 2008

Abstract
Resistance to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2L) limits its potential as a drug for cancer therapy. Here, we report that kaempferol, a bioactive plant flavonoid, sensitizes U251 and U87 glioma cells to TRAIL-mediated apoptosis. In contrast, U373 cells are not affected by kaempferol treatment. Treatment of kaempferol alone for 24 h did not induce apoptosis in the cell lines. We provide evidence that TRAIL-induced apoptosis is partially driven by kaempferol-mediated reduction of survivin protein levels. On kaempferol treatment, proteasomal degradation of survivin was observed. Inhibition of proteasomal degradation with MG132 in kaempferol-treated cells restored survivin protein levels in both glial cell lines. Consequently, overexpression of survivin attenuated TRAIL-kaempferol–induced apoptosis. In addition, we show that kaempferol mediates down-regulation of phosphorylated Akt, thereby further reducing survivin protein level. Furthermore, the blockage of the serine/threonine kinase Akt activity by kaempferol is important for inhibition of survivin because active phosphorylated Akt enhances the stability of survivin. However, we also show that the combined treatment of TRAIL and kaempferol induces cleavage (activation) of caspase-8, thereby exerting a proapoptotic effect independent of survivin known not to inhibit caspase-8 activation. Other effects induced by kaempferol were suppression of X-linked inhibitor of apoptosis proteins as the antiapoptotic members of the Bcl-2 family, Bcl-2, Bcl-xL, and Mcl-1 in a concentration-dependent manner. In summary, we showed that suppression of survivin is an essential mechanism in TRAIL-kaempferol–mediated apoptosis. [Mol Cancer Ther 2008;7(11):3566–74]