bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycoengineering the N-acyl side chain of sialic acid of human erythropoietin affects its resistance to sialidase
Authors: Werner Anselm , Horstkorte Rüdiger , Glanz Dagobert , Biskup Karina , Blanchard Véronique , Berger Markus , Bork Kaya 
Published: August 2012

Abstract
During the last years, the use of therapeutic glycoproteins has increased strikingly. Glycosylation of recombinant glycoproteins is of major importance in biotechnology, as the glycan composition of recombinant glycoproteins impacts their pharmacological properties. The terminal position of N-linked complex glycans in mammals is typically occupied by sialic acid. The presence of sialic acid is crucial for functionality and affects the half-life of glycoproteins. However, glycoproteins in the bloodstream become desialylated over time and are recognized by the asialoglycoprotein receptors via the exposed galactose and targeted for degradation. Non-natural sialic acid precursors can be used to engineer the glycosylation side chains by biochemically introducing new non-natural terminal sialic acids. Previously, we demonstrated that the physiological precursor of sialic acid (i.e., N-acetylmannosamine) can be substituted by the non-natural precursors N-propanoylmannosamine (ManNProp) or N-pentanoylmannosamine (ManNPent) by their simple application to the cell culture medium. Here, we analyzed the glycosylation of erythropoietin (EPO). By feeding cells with ManNProp or ManNPent, we were able to incorporate N-propanoyl or N-pentanoyl sialic acid in significant amounts into EPO. Using a degradation assay with sialidase, we observed a higher resistance of EPO to sialidase after incorporation of N-propanoyl or N-pentanoyl sialic acid.
Processive proteolysis by γ-secretase and the mechanism of Alzheimer’s disease
Authors: Wolfe Michael S. 
Published: August 2012

Abstract
γ-Secretase is a membrane-embedded protease complex with presenilin as the catalytic component. Cleavage within the transmembrane domain of the amyloid β-protein precursor (APP) by γ-secretase produces the C-terminus of the amyloid β-peptide (Aβ), a proteolytic product prone to aggregation and strongly linked to Alzheimer’s disease (AD). Presenilin mutations are associated with early-onset AD, but their pathogenic mechanisms are unclear. One hypothesis is that these mutations cause AD through a toxic gain of function, changing γ-secretase activity to increase the proportion of 42-residue Aβ over the more soluble 40-residue form. A competing hypothesis is that the mutations cause AD through a loss of function, by reducing γ-secretase activity. However, γ-secretase apparently has two types of activities, an endoproteolytic function that first cuts APP to generate a 48/49-residue form of Aβ, and a carboxypeptidase activity that processively trims these longer Aβ intermediates approximately every three residues to form shorter, secreted forms. Recent studies suggest a resolution of the gain-of-function vs. loss-of-function debate: presenilin mutations may increase the proportion of longer, more aggregation-prone Aβ by specifically decreasing the trimming activity of γ-secretase. That is, the reduction of this particular proteolytic function of presenilin, not its endoproteolytic activity, may lead to the neurotoxic gain of function.
Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice
Authors: Dauth Stephanie , Schmidt Maike M. , Rehders Maren , Dietz Frank , Kelm Sørge , Dringen Ralf , Brix Klaudia 
Published: August 2012

Abstract
Cathepsin K is important for the brain, because its deficiency in mice is associated with a marked decrease in differentiated astrocytes and changes in neuronal patterning in the hippocampus as well as with learning and memory deficits. As cathepsin K activity is most prominent in hippocampal regions of wild type animals, we hypothesised alterations in astrocyte-mediated support of neurons as a potential mechanism underlying the impaired brain functions in cathepsin K-deficient mice. To address this hypothesis, we have generated and characterised astroglia-rich primary cell cultures from cathepsin K-deficient and wild type mice and compared these cultures for possible changes in metabolic support functions and cell composition. Interestingly, cells expressing the oligodendrocytic markers myelin-associated glycoprotein and myelin basic protein were more frequent in astroglia-rich cultures from cathepsin K-deficient mice. However, cell cultures from both genotypes were morphologically comparable and similar with respect to glucose metabolism. In addition, specific glutathione content, glutathione export and γ-glutamyl-transpeptidase activity remained unchanged, whereas the specific activities of glutathione reductase and glutathione-S-transferase were increased by around 50% in cathepsin K-deficient cultures. Thus, lack of cathepsin K in astroglia-rich cultures appears not to affect metabolic supply functions of astrocytes but to facilitate the maturation of oligodendrocytes.
Glycan profiles of the 27 N-glycosylation sites of the HIV envelope protein CN54gp140
Authors: Pabst Martin , Chang Martina , Stadlmann Johannes , Altmann Friedrich 
Published: August 2012

Abstract
Hope rests on the envelope proteins of human immunodeficiency virus (HIV) as protective vaccines and thus their antibody binding sites are of prime interest. 2G12 and other human antibodies bind to a cluster of oligomannose N-glycans. Owing to the extreme number and density of N-glycosylation sites gp160 and its recombinant form gp140 represent challenging tasks for site-specific glycosylation analysis. We have conducted a glycosylation analysis of CN54gp140 by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) using an ion trap as well as a Q-TOF instrument and standard software for glycopeptide identification. First, a deglycosylated sample of the protease digest served to locate the elution positions of peptides covering all of the 27 potential N-glycosylation sites. Then, the assignments of the similarly eluting glycopeptides were verified by collision-induced decay MS/MS experiments with elevated fragmentation energy. The acquisition of site-specific glycan profiles was facilitated by the use of buffered eluent, which rounds up all glycoforms of a peptide into one peak. Calculation of the molecular mass drawn on the weighted averages of the glycans at each site led to the actual mass of gp140 of approximately 120 kDa.
Structural determinants of the eosinophil cationic protein antimicrobial activity
Authors: Boix Ester , Salazar Vivian A. , Torrent Marc , Pulido David , Nogués M. Victòria , Moussaoui Mohammed 
Published: August 2012

Abstract
Antimicrobial RNases are small cationic proteins belonging to the vertebrate RNase A superfamily and endowed with a wide range of antipathogen activities. Vertebrate RNases, while sharing the active site architecture, are found to display a variety of noncatalytical biological properties, providing an excellent example of multitask proteins. The antibacterial activity of distant related RNases suggested that the family evolved from an ancestral host-defence function. The review provides a structural insight into antimicrobial RNases, taking as a reference the human RNase 3, also named eosinophil cationic protein (ECP). A particular high binding affinity against bacterial wall structures mediates the protein action. In particular, the interaction with the lipopolysaccharides at the Gram-negative outer membrane correlates with the protein antimicrobial and specific cell agglutinating activity. Although a direct mechanical action at the bacteria wall seems to be sufficient to trigger bacterial death, a potential intracellular target cannot be discarded. Indeed, the cationic clusters at the protein surface may serve both to interact with nucleic acids and cell surface heterosaccharides. Sequence determinants for ECP activity were screened by prediction tools, proteolysis and peptide synthesis. Docking results are complementing the structural analysis to delineate the protein anchoring sites for anionic targets of biological significance.
Insights into the modulation of optimum pH by a single histidine residue in arginine deiminase from Pseudomonas aeruginosa
Authors: Ding Hanjing , Liu Hui , Yin Yan , Ding Ying , Jia Yan , Chen Qingming , Zou Guolin , Zheng Zhongliang 
Published: August 2012

Abstract
Arginine deiminase (ADI) is a potential antitumor agent for the arginine deprivation treatment of l-arginine auxotrophic tumors. The optimum pH of ADI varies significantly, yet little is known about the origin of this variety. Here, Pseudomonas aeruginosa ADI (PaADI), an enzyme that functions only at acidic pH, was utilized as the model system. The results of UV-pH titration imply that the nucleophilic Cys406 thiol group is protonated in the resting state. The H405R single mutation resulted in an altered pH optimum (from pH 5.5 to 6.5), an increased k
cat (from 9.8 s-1 to 101.7 s-1 at pH 6.5), and a shifted pH rate dependence (ascending limb pK
a from 3.6 to 4.4). Other mutants were constructed to investigate the effects of hydrogen bonding, charge distribution, and hydrophobicity on the properties of the enzyme. The pH optima of His405 mutants were all shifted to a relatively neutral pH except for the H405E mutant. The results of kinetic characterizations and molecular dynamic simulations revealed that the active site hydrogen bonding network involving Asp280 and His405 plays an important role in controlling the dependence of PaADI activity on pH. Moreover, the H405R variant showed increased cytotoxicity towards arginine auxotrophic cancer cell lines.
Perinatal risks after IVF and ICSI
Authors: Zollner Ursula , Dietl Johannes 
Published: August 2012

Abstract
Pregnancies that occur after infertility treatment, particularly after assisted reproduction, constitute high-risk pregnancies. Occurrences of conditions such as high blood pressure, preeclampsia, growth retardations and bleeding are higher in comparison with the norm of spontaneously entered pregnancies. The rate of premature births and the frequency of intrauterine deaths are much higher than the average for all pregnancies. Furthermore, pregnancies resulting from in-vitro fertilisation (IVF) have significantly higher rates of requiring induced labour or caesarean section. However, it is to be assumed that these complications and unfortunate developments are not caused by extracorporeal fertilisation itself, but rather are due to the frequency of multiples and to the risk factors of the women involved. These women are, on average, older and there are often more problems with cycle irregularities, uterine anomalies and obesity than in the total collective of all pregnancies. The methods of modern reproductive medicine often bring a higher rate of multiple pregnancies. The clinical problem of multiple pregnancies is, above all, the raised rate of premature births and intrauterine growth retardations that contribute to the significantly higher rate of morbidity and mortality for these children. The slightly higher rate of congenital defects after IVF and intracytoplasmic sperm injection (ICSI) are also attributed more to the risk profile of the parents and less to the techniques themselves. The most important and easy-to-avoid complication is the multiple pregnancy, and it should be our goal to lower this rate even further.
What do we know when we claim to know nothing? Partial knowledge of word meanings may be ontological, but not hierarchical
Authors: Stein Jeannette M. , Shore Wendelyn J. 
Published: August 2012

AbstractTwo studies investigated whether knowledge about ontological category membership exists early in the word learning process—specifically, when words are partially known—and if so, how such knowledge is represented. Participants made decisions about the ontological category membership of words at three levels of knowledge: words they correctly defined (known), words recognized as familiar (frontier), and words mistakenly identified as nonwords (unknown). Accuracy on this task improved as a function of word level. Participants were able to identify the broad ontological categories to which words at all three levels of knowledge belonged, as well as the more specific ontological categories to which the words belonged. Overall, results indicated that knowledge about ontological category membership is available for words at very low levels of knowledge, and that this knowledge does not necessarily follow the strict hierarchical organization some ontological systems are thought to embody (e.g. Keil 1979). Implications for the acquisition and representation of word meanings are discussed.
Elicited imitation as a measure of morphemic accuracy: Evidence from L2 Spanish
Authors: West Donna E. 
Published: August 2012

AbstractThis study measures whether number and type of morphemes in an elicited imitation string result in a greater number of modifications with L2 experience. Rationale is drawn from L2 working memory processing limitations at distinct levels of proficiency. 38 subjects (L2 Spanish university students) comprise three proficiency groups: beginning, undergraduate majors and graduate students. Number of morphemes was varied within each syllable count; and responses were either correct or modified (lexemically/inflectionally as deletions or substitutions). One or two way ANOVAs determined significance between mean proportions for each group. Findings indicate that increases in number of morphemes yielded significant differences, and that while the lowest proficiency group produced higher proportions of lexical deletions, the modifications made by more advanced groups were inflectional substitutions.
Investigation of fracture toughness parameters of epoxy nanocomposites for different crack angles
Authors: Fereidoon Abdolhossein , Mottahedin Lia , Latibari Sara Tahan 
Published: August 2012

Abstract
The effects of single-walled carbon nanotubes (SWCNTs) on the mechanical properties of nanocomposites with epoxy matrix were studied, with the emphasis on fracture toughness under tensile loading conditions. It has been demonstrated that adding CNTs into polymer-based materials can improve the mechanical properties of this material. CNTs possess a certain potential to improve the fracture toughness of epoxy systems due to their mechanical properties and increase the fracture toughness of nanocomposites. Since the fracture toughness parameters were best manifested in the scaling properties and were the main parameters, the angles of different cracks have been simulated in a 3D finite element framework and the effects of different angles of crack, on the fracture toughness of polymers, have been modeled and investigated. The simulations are run for different bias angles. The influence of angle, the crack lengths and the variations of different lengths of nanocomposite in different volume fractions (vol%) are investigated. That is to say, at first, nanocomposites had a significantly higher fracture toughness compared to the pure epoxy. We found that nanocomposites, in the presence of SWCNTs, had a greater effect on fracture toughness of nanocomposites in a greater volume of fractions. Also, the nanocomposites exhibited a significant increase in fracture toughness, with zero angle of crack compared with greater angles. In addition, it is found that at a constant volume fracture, fracture toughness, increases by increasing crack lengths.
Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia
Authors: Camargo Carlos A. , Ganmaa Davaasambuu , Frazier A. Lindsay , Kirchberg Franca F. , Stuart Jennifer J. , Kleinman Ken , Sumberzul Nyamjav , Rich-Edwards Janet W. 
Published: August 2012

OBJECTIVE:
Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs.

METHODS:
By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January–March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D3 (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months.

RESULTS:
At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5–10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P &lt; .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31–0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28–0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; Pinteraction = .27).

CONCLUSIONS:
Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency.
Craniofacial Stability in Patients with Crouzon or Apert Syndrome after Le Fort III Distraction Osteogenesis
Authors: Reitsma Jacobus H. , Ongkosuwito Edwin M. , Buschang Peter H. , Adrichem Léon N.A. V , Prahl-Andersen Birte 
Published: August 2012

Objective Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients with Crouzon or Apert syndrome. Design Population-based case-control study. Patients and Methods Records of patients with the syndrome of Crouzon (N = 6) or Apert (N = 7) were compared, before and after Le Fort III DO, with a nonsyndromic untreated control group (N = 486). Main Outcome Measures Sagittal and vertical cephalometric maxillary landmarks and measurements were used to predict and measure midface advancement and rotation after Le Fort III DO. Cephalograms were taken before surgery (T0), 4 months after surgery at removal of the distraction device (T1), and 1 year after removal of the distraction device (T2). Analysis Z scores were performed to compare cephalometric measures of syndromic patients with control subjects. Results Cephalograms of 13 patients with Crouzon syndrome (N = 6) or Apert (N = 7) (age range 8.2 to 19.8 years) were evaluated. Treatment changes (T1-T2) showed statistically significant maxillary advancement, with no significant differences between the patients with the Crouzon or Apert syndrome. Conclusions DO of the midface in patients with Crouzon or Apert syndrome seems to be stable in the sagittal direction after follow-up. Although Crouzon and Apert differ after DO, anteroposterior craniofacial dimensions were significantly improved and were closer to patterns of normal subjects.
Randomized Multicenter and Stratified Phase II Study of Gemcitabine Alone Versus Gemcitabine and Docetaxel in Patients with Metastatic or Relapsed Leiomyosarcomas: A Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study)
Authors: Pautier Patricia , Floquet Anne , Penel Nicolas , Piperno-Neumann Sophie , Isambert Nicolas , Rey Annie , Bompas Emmanuelle , Cioffi Angela , Delcambre Corinne , Cupissol Didier , Collin Françoise , Blay Jean-Yves , Jimenez Marta , Duffaud Florence 
Published: August 2012

Abstract

Background.
This study aimed to evaluate the efficacy and toxicity of single-agent gemcitabine versus gemcitabine plus docetaxel as second-line therapy in patients with uterine and nonuterine leiomyosarcoma (LMS).

Patients and Methods.
Patients had metastatic or unresectable LMS and had received one prior anthracycline-based regimen. A total of 90 patients received either single-agent gemcitabine (arm A; gemcitabine, 1,000 mg/m2 i.v. for 100 minutes on days 1, 8, and 15 of a 28-day cycle) or a combination of gemcitabine and docetaxel (arm B; gemcitabine, 900 mg/m2 i.v. for 90 minutes on days 1 and 8, plus docetaxel, 100 mg/m2 i.v. for 1 hour on day 8 of a 21-day cycle with lenograstim). The primary endpoint was the objective response rate.

Results.
The objective response rates were 19% and 24% in arm A (gemcitabine) and arm B (gemcitabine plus docetaxel), respectively, for patients with uterine LMS. For patients with nonuterine LMS, the objective response rates were 14% and 5% for arms A and B, respectively. The median progression-free survival times for arms A and B were 5.5 months and 4.7 months, respectively, for patients with uterine LMS. For patients with nonuterine LMS, the median progression-free survival times were 6.3 months and 3.8 months for arms A and B, respectively. One toxic death occurred in arm B.

Conclusions.
Both single-agent gemcitabine and gemcitabine plus docetaxel were found to be effective second-line therapies for leiomyosarcomas, with a 3-month progression-free survival rate of 40% for LMS with both uterine and nonuterine sites of origin. Single-agent gemcitabine yielded results similar to those of gemcitabine plus docetaxel in this trial, but patients using single-agent gemcitabine experienced less toxicity.
Hospitalization patterns and outcomes of infants with Influenza A(H1N1) in Kuwait
Authors: Husain Entesar H , AlKhabaz Ahmad , Al-Qattan Hanan Y , Al-Shammari Nufoud , Owayed Abdullah F 
Published: August 2012

Introduction: Infants represent an important risk group for influenza associated hospitalizations and mortality. This study evaluated the clinical presentations, hospitalization course and outcome of infants hospitalized with the pandemic influenza A H1N1 [Influenza A(H1N1)pdm09] in relation to their previous health status. Methodology: We conducted a retrospective chart review of hospitalized infants with laboratory-confirmed Influenza A(H1N1)pdm09 infection in two hospitals in Kuwait. Demographic characteristics, pre-existing high-risk medical conditions, clinical presentations, complications and mortality were analyzed. Previously healthy infants’ data were compared with infants with pre-existing high-risk medical conditions for severity of the illness and outcome. Results: We identified 62 infants comprising 32% of all admissions with Influenza A(H1N1)pdm09. The median age ± SD was 7 ± 4 months. Nineteen (31%) had pre-existing high-risk medical conditions. Complications were documented in 53% of previously healthy infants compared to 47% in high-risk infants. Mean duration of hospitalization was 4.9 days in healthy infants and 6.7 for infants with high-risk medical conditions. Bacterial pneumonia complicated 7% of previously healthy infants compared to 26% with high-risk conditions (P = 0.03). Four infants (6.5%) required admission to the intensive care unit (ICU), of whom three had high risk medical condition. Conclusion: The majority of hospitalized infants with Influenza A(H1N1)pdm09 were previously healthy. Prolonged hospitalization, ICU admission and mortality were more observed in infants with high-risk medical conditions. According to the latest Advisory Committee on Immunization Practices (ACIP) recommendations, annual influenza vaccination is recommended for any child six months of age and older, particularly those with risk factors.