bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting
Authors: Noranate Nitchakarn , Prugnolle Franck , Jouin Hélène , Tall Adama , Marrama Laurence , Sokhna Cheikh , Ekala Marie-Thérèse , Guillotte Micheline , Bischoff Emmanuel , Bouchier Christiane , Patarapotikul Jintana , Ohashi Jun , Trape Jean-François , Rogier Christophe , Mercereau-Puijalon Odile 
Published: October 2009

AbstractBackgroundGenetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity againstPlasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial.ResultsFamily distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles.ConclusionThePfmsp1block2 locus presents a very large population sequence diversity. The lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. The locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. There is no evidence of positive selection for intra-family sequence diversity, consistent with the observed characteristics of the antibody response.
Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor
Authors: Jönsson Mats , Ekstrand Anna , Edekling Thomas , Eberhard Jakob , Grabau Dorthe , Borg David , Nilbert Mef 
Published: October 2009

Abstract

Background

KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.

Methods
We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors.

Results

KRAS mutations were significantly more often found in rectal cancer (21/38, 55%) than in colon cancer (32/98, 33%) (P = 0.02). This finding was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers (P = 0.01). Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp/Gly13Asp and Gly12Cys/Gly13Asp and a third tumor carried Gly12Cys/Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component.

Conclusion
The demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti-EGFR therapies, whereas the observation of concurrent KRAS mutations imply that repeated KRAS targeting may occur during tumor progression in a subset of colorectal cancers.
Meta-analysis: Adefovir dipivoxil in combination with lamivudine in patients with lamivudine-resistant hepatitis B virus
Authors: Chen En-Qiang , Wang Li-Chun , Lei Jun , Xu Lu , Tang Hong 
Published: October 2009

AbstractBackgroundCurrently, there are no conclusive results on the efficacy of adefovir dipivoxil (ADV) plus lamivudine (LAM) in LAM-resistant patients with chronic hepatitis B (CHB). The aim of study was to evaluate the efficacy of rescue therapy with ADV plus LAM compared to ADV monotherapy in LAM-resistant CHB patients.ResultsWe searched PUBMED, EMBASE, Web of Science, CNKI (National Knowledge Infrastructure), VIP database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Six eligible trials (442 patients in total) were included and evaluated for methodologic quality and heterogeneity. Greater virological response and lower emergence rate of ADV-associated mutants was observed in ADV plus LAM compared to ADV monotherapy (bothP< 0.05). On the contrary, the rate of ALT normalization, HBeAg clearance and seroconversion were all similar between ADV plus LAM and ADV (allP> 0.05). Additionally, adding-on or switch-to ADV was both well tolerated.ConclusionThe combination of ADV with LAM was superior in inhibiting HBV replication and preventing drug resistance as compared to ADV alone for LAM-resistant CHB patients.
Characterization of intracortical synaptic connections in the mouse anterior cingulate cortex using dual patch clamp recording
Authors: Wu Long-Jun , Li Xiangyao , Chen Tao , Ren Ming , Zhuo Min 
Published: October 2009

SummaryThe anterior cingulate cortex (ACC) is involved in sensory, cognitive, and executive functions. Studies of synaptic transmission and plasticity in the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions. Previous anatomic studies suggest complex local interactions among neurons within the ACC. However, there is a lack of functional studies of such synaptic connections between ACC neurons. In the present study, we characterized the neuronal connections in the superficial layers (I-III) of the mouse ACC using dual whole-cell patch clamp recording technique. Four types of synaptic connections were observed, which are from a pyramidal neuron to a pyramidal neuron, from a pyramidal neuron to an interneuron, from an interneuron to a pyramidal neuron and from an interneuron to an interneuron. These connections exist among neurons in layer II/III or between neurons located layer I and II/III, respectively. Moreover, reciprocal connections exist in all four types of paired neurons. Our results provide the first key evidence of functional excitatory and inhibitory connections in the ACC.
The prognostic value of baseline erosions in undifferentiated arthritis
Authors: Thabet Mohamed M , Huizinga Thomas WJ , van der Heijde Désirée M , van der Helm-van Mil Annette HM 
Published: October 2009

AbstractIntroductionUndifferentiated arthritis (UA) has a variable disease course; 40 to 50% of UA patients remit spontaneously, while 30% develop rheumatoid arthritis (RA). Identifying the UA patients who will develop RA is essential to initiate early disease-modifying anti-rheumatic drug (DMARD) therapy. Although the presence of bone erosions at baseline is predictive for a severe destructive disease course in RA, the prognostic importance of erosive joints for disease outcome in UA is unknown. This study evaluates the predictive value of erosive joints for the disease outcome in UA as measured by RA development and disease persistency.MethodsBaseline hands and feet radiographs of 518 UA patients were evaluated for erosions using a clinical definition as well as the Sharp/van der Heijde method. After 1 year follow-up, patients were re-assessed for the fulfilment of the 1987 ACR classification criteria for RA. Disease persistency was defined as the absence of sustained remission during all available follow-up (mean 8 ± 3 years).ResultsAt baseline, 28.6% of UA patients had erosive joints. Presence of ≥2 erosive joints showed a positive predictive value for RA development of 53% and for persistent disease of 68%. Patients with erosions that did not develop RA were less often anticyclic citrullinated peptide antibody (ACPA)+ve, rheumatoid factor (RF)+ve and had lower C-reactive protein (CRP), erythrocytic sedimentation rate (ESR) and number of swollen joints compared to those who developed RA. Feet erosions are equally predictive compared to erosions at hands.ConclusionsPresence of ≥2 erosive joints at baseline in UA patients gives a risk for RA development of 53% and for persistent disease of 68%, indicating that erosions in UA are not always predictive for unfavorable disease outcomes.
Transcriptome analysis of functional differentiation between haploid and diploid cells of Emiliania huxleyi, a globally significant photosynthetic calcifying cell
Authors: von Dassow Peter , Ogata Hiroyuki , Probert Ian , Wincker Patrick , Da Silva Corinne , Audic Stéphane , Claverie Jean-Michel , de Vargas Colomban 
Published: October 2009

Abstract
Background
Eukaryotes are classified as either haplontic, diplontic, or haplo-diplontic, depending on which ploidy levels undergo mitotic cell division in the life cycle. Emiliania huxleyi is one of the most abundant phytoplankton species in the ocean, playing an important role in global carbon fluxes, and represents haptophytes, an enigmatic group of unicellular organisms that diverged early in eukaryotic evolution. This species is haplo-diplontic. Little is known about the haploid cells, but they have been hypothesized to allow persistence of the species between the yearly blooms of diploid cells. We sequenced over 38,000 expressed sequence tags from haploid and diploid E. huxleyi normalized cDNA libraries to identify genes involved in important processes specific to each life phase (2N calcification or 1N motility), and to better understand the haploid phase of this prominent haplo-diplontic organism.

Results
The haploid and diploid transcriptomes showed a dramatic differentiation, with approximately 20% greater transcriptome richness in diploid cells than in haploid cells and only ≤ 50% of transcripts estimated to be common between the two phases. The major functional category of transcripts differentiating haploids included signal transduction and motility genes. Diploid-specific transcripts included Ca2+, H+, and HCO3- pumps. Potential factors differentiating the transcriptomes included haploid-specific Myb transcription factor homologs and an unusual diploid-specific histone H4 homolog.

Conclusions
This study permitted the identification of genes likely involved in diploid-specific biomineralization, haploid-specific motility, and transcriptional control. Greater transcriptome richness in diploid cells suggests they may be more versatile for exploiting a diversity of rich environments whereas haploid cells are intrinsically more streamlined.
Removal of Lead(II) Ions from Aqueous Solutions Using Manganese Oxide-Coated Adsorbents: Characterization and Kinetic Study
Authors: Boujelben N. , Bouzid J. , Elouear Z. 
Published: October 2009

Manganese oxide-coated sand (MOCS) and manganese oxide-coated crushed brick (MOCB) were characterized and employed for the removal of Pb(II) ions from aqueous solution. Scanning electron microscopy (SEM), FT-IR, X-ray diffraction (XRD) methods and BET analyses were used to study the surface properties of the adsorbents. Adsorption of Pb(II) ions from aqueous solutions was investigated by batch experiments. The estimated optimum pH for Pb(II) ion retention by the considered adsorbents was 5. Both the Freundlich and Langmuir isotherms provided a reasonable fit to the experimental data for the adsorption of Pb(II) ions. The adsorption capacities of the coated adsorbents at a pH value of 5 and a temperature of 20 °C were 0.029 mmol/g and 0.030 mmol/g for MOCS and MOCB, respectively. The adsorption kinetics were tested using the pseudo-first-order and pseudo-second-order equations as well as the intraparticle diffusion model, with the rate constants from the three kinetic models being calculated. The best correlation coefficients were obtained using the pseudo-second-order kinetic model. Results from this study suggest that the manganese oxide-coated sorbent is potentially suitable for the removal of Pb(II) ions from aqueous solutions.
Adsorption and Movement of Carbofuran in Four Different Soils Varying in Physical and Chemical Properties
Authors: Singh R.P. , Srivastava Garima 
Published: October 2009

Laboratory studies were conducted to determine the adsorption and movement of carbofuran on four divergent textured Indian soils at a fixed volume fraction (fs = 0.1) of methanol/water mixtures using batch equilibrium and soil thin layer chromatography (soil TLC) techniques. The measured equilibrium adsorption isotherms for silt loam (FSL and ASL) and loam (KL) soils were L-shaped and for sandy loam (BSL) soil S-shaped, all being well fitted by the Freundlich isotherm. A higher adsorption of carbofuran was observed on FSL followed by ASL, KL and BSL soils as anticipated by the values obtained for the Freundlich constant, KF and partition coefficient, KD. The Frontal Retardation factor (FRf) values obtained from soil TLC studies were inversely proportional to the KF and KD values. The affinity of carbofuran towards organic carbon, organic matter and clay content of the soils was evaluated by calculating the KOC, KOM and KC values. The negative magnitude of the Gibbs'free energy (ΔG0) indicated the spontaneity of the adsorption of carbofuran onto the soils studied. The leaching index (LI) of carbofuran calculated for the soils studied indicated its high potential to leach into shallow aquifers and ground water. Pearson's correlations calculated for KF and KD against the soil properties showed a highly significant correlation with the clay + silt content of the soils. Multiple regression of KF and KD against the soil properties indicated that the mineral content of the soils (clay and clay + silt) is the best predictor of carbofuran adsorption, followed by soil pH. Predicted log KOM values were also evaluated by using the aqueous solubility, the 1-octanol/ water partition coefficient (KOW), the adsorbability index (AI) and the first-order molecular connectivity index (1χ) of carbofuran. Use of the aqueous solubility, and the 1-octanol/water partition coefficient (KOW) to predict the extent of adsorption gave values which displayed a considerable error in comparison to those measured experimentally, whereas the use of the adsorbability index (AI) and the first-order molecular connectivity index (1χ) of carbofuran improved the predictions considerably.
Dependence of bone yield (volume of bone formed per unit of cement surface area) on resorption cavity size during osteonal remodeling in human rib: implications for osteoblast function and the pathogenesis of age-related bone loss
Authors: Qiu Shijing , Rao D Sudhaker , Palnitkar Saroj , Parfitt A Michael 
Published: October 2009

Abstract
It is both a necessary and a sufficient condition for bone to be lost with age at any surface location that during remodeling the replacement of resorbed bone is incomplete. In both the ilium and the rib, the degree of such focal imbalance is smaller on the intracortical than on the endocortical or cancellous surfaces that are adjacent to bone marrow. The reason for this difference is unknown. To further examine this question, we measured various geometric variables in 1263 osteons in rib cross sections from 65 persons, including both sexes and age ranges 20 to 30 years and 60 to 70 years (four groups). Haversian canal (HC) area did not differ significantly between sexes or age groups. Percent osteonal refilling was close to 95% in all groups and did not differ between sexes but fell slightly with age. There was a very highly significant linear relationship between osteon bone area and (osteon area + HC area) in all groups, with coefficients of determination (r2) greater than 0.98. The regression slopes declined slightly with age in women but not in men. There was a very highly significant quadratic relationship between osteon bone area and osteon perimeter in all groups, with r2 values greater than 0.97. The ratio osteon bone area:osteon perimeter, an index of bone yield—the volume of bone deposited on each unit area of cement surface—was strongly related to osteon area and did not differ between sexes but was slightly less in the older groups. We conclude the following: (1) The high efficiency of intracortical remodeling in the rib is confirmed, with only trivial effects of age. (2) For HC area to be maintained within narrow limits and bone balance preserved, either initial osteoblast density or osteoblast capacity (the two determinants of bone yield) or, most likely, both must increase progressively with the size of the resorption cavity, suggesting that osteoblast recruitment (relative to available surface) and osteoblast lifespan increase with the volume of bone resorbed. (3) Intracortical remodeling in the rib is more efficient than marrow-adjacent remodeling at any site, possibly because of the different relationships to the circulation. In osteonal remodeling, all molecules released from resorbed bone must travel past the sites of osteoblast recruitment and operation, but in hemiosteonal remodeling, some molecules may not be subject to this constraint. (4) If marrow-adjacent remodeling became as efficient as rib intracortical remodeling, age-related bone loss would cease to be an important medical problem. © 2010 American Society for Bone and Mineral Research
Obesity and fractures in postmenopausal women
Authors: Premaor Melissa Orlandin , Pilbrow Lesley , Tonkin Carol , Parker Richard A , Compston Juliet 
Published: October 2009

Abstract
Low body mass index (BMI) is a recognized risk factor for fragility fracture, whereas obesity is widely believed to be protective. As part of a clinical audit of guidance from the National Institute of Health and Clinical Excellence (NICE), we have documented the prevalence of obesity and morbid obesity in postmenopausal women younger than 75 years of age presenting to our Fracture Liaison Service (FLS). Between January 2006 and December 2007, 1005 postmenopausal women aged less than 75 years with a low-trauma fracture were seen in the FLS. Of these women, 805 (80%) underwent assessment of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA), and values for BMI were available in 799. The prevalence of obesity (BMI 30 to 34.9 kg/m2) and morbid obesity (BMI ≥ 35 kg/m2) in this cohort was 19.3% and 8.4%, respectively. Normal BMD was reported in 59.1% of obese and 73.1% of morbidly obese women, and only 11.7% and 4.5%, respectively, had osteoporosis (p &lt; .0001). Multiple regression analysis revealed significant negative associations between hip T-score and age (p &lt; .0001) and significant positive associations with BMI (p &lt; .0001) and previous fracture (p = .001). Our results demonstrate a surprisingly high prevalence of obesity in postmenopausal women presenting to the FLS with low-trauma fracture. Most of these women had normal BMD, as measured by DXA. Our findings have important public heath implications in view of the rapidly rising increase in obesity in many populations and emphasize the need for further studies to establish the pathogenesis of fractures in obese individuals and to determine appropriate preventive strategies. © 2010 American Society for Bone and Mineral Research
Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA-binding-independent actions of the ERα
Authors: Almeida Maria , Martin-Millan Marta , Ambrogini Elena , Bradsher Robert , Han Li , Chen Xiao-Dong , Roberson Paula K , Weinstein Robert S , O'Brien Charles A , Jilka Robert L , Manolagas Stavros C 
Published: October 2009

Abstract
Estrogens diminish oxidative stress in bone and bone marrow, attenuate the generation of osteoblasts, and decrease the prevalence of mature osteoblast apoptosis. We have searched for the molecular mechanism of these effects using as tools a mouse model bearing an estrogen receptor α (ERα) knock-in mutation that prevents binding to DNA (ERαNERKI/−) and several osteoblast progenitor cell models expressing the wild-type ERα or the ERαNERKI/−. We report that the ability of estrogens to diminish the generation of reactive oxygen species, stimulate the activity of glutathione reductase, and decrease the phosphorylation of p66shc, as well as osteoblastogenesis and osteoblast number and apoptosis, were fully preserved in ERαNERKI/− mice, indicating that the DNA-binding function of the ERα is dispensable for all these effects. Consistent with the attenuation of osteoblastogenesis in this animal model, 17β-estradiol attenuated bone morphogenetic protein 2 (BMP-2)–induced gene transcription and osteoblast commitment and differentiation in murine and human osteoblastic cell lines. Moreover, 17β-estradiol attenuated BMP-2-induced differentiation of primary cultures of calvaria- or bone marrow–derived osteoblastic cells from ERαNERKI/− mice as effectively as in cells from wild-type littermates. The inhibitory effect of the hormone on BMP-2 signaling resulted from an ERα-mediated activation of ERKs and the phosphorylation of Smad1 at the linker region of the protein, which leads to proteasomal degradation. These results illustrate that the effects of estrogens on oxidative stress and the birth and death of osteoblasts do not require the binding of ERα to DNA response elements, but instead they result from the activation of cytoplasmic kinases. © 2010 American Society for Bone and Mineral Research