bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Antibody Fragments with a ControlledN-Glycosylation Pattern and Induction of Endoplasmic Reticulum-Derived Vesicles in Seeds of Arabidopsis
Authors: Loos Andreas , Van Droogenbroeck Bart , Hillmer Stefan , Grass Josephine , Pabst Martin , Castilho Alexandra , Kunert Renate , Liang Mifang , Arcalis Elsa , Robinson David G. , Depicker Ann , Steinkellner Herta 
Published: February 2011

AbstractIntracellular trafficking and subcellular deposition are critical factors influencing the accumulation and posttranslational modifications of proteins. In seeds, these processes are not yet fully understood. In this study, we set out to investigate the intracellular transport, final destination, N-glycosylation status, and stability of the fusion of recombinant single-chain variable fragments to the crystallizing fragment of an antibody (scFv-Fc) of two antiviral monoclonal antibodies (2G12 and HA78). The scFv-Fcs were expressed in Arabidopsis (Arabidopsis thaliana) seeds and leaves both as secretory molecules and tagged with an endoplasmic reticulum (ER) retention signal. We demonstrate differential proteolytic degradation of scFv-Fcs in leaves versus seeds, with higher degradation in the latter organ. In seeds, we show that secretory versions of HA78 scFv-Fcs are targeted to the extracellular space but are deposited in newly formed ER-derived vesicles upon KDEL tagging. These results are in accordance with the obtained N-glycosylation profiles: complex-type and ER-typical oligomannosidic N-glycans, respectively. HA78 scFv-Fcs, expressed in seeds of an Arabidopsis glycosylation mutant lacking plant-specific N-glycans, exhibit custom-made human-type N-glycosylation. In contrast, 2G12 scFv-Fcs carry exclusively ER-typical oligomannosidic N-glycans and were deposited in newly formed ER-derived vesicles irrespective of the targeting signals. HA78 scFv-Fcs exhibited efficient virus neutralization activity, while 2G12 scFv-Fcs were inactive. We demonstrate the efficient generation of scFv-Fcs with a controlled N-glycosylation pattern. However, our results also reveal aberrant subcellular deposition and, as a consequence, unexpected N-glycosylation profiles. Our attempts to elucidate intracellular protein transport in seeds contributes to a better understanding of this basic cell biological mechanism and is a step toward the versatile use of Arabidopsis seeds as an alternative expression platform for pharmaceutically relevant proteins.
Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso‐occlusive crises in patients with sickle cell disease: a phase III randomized, placebo‐controlled, double‐blind study of the gardos channel blocker senicapoc (ICA‐17043)
Authors: Ataga Kenneth I. , Reid Marvin , Ballas Samir K. , Yasin Zahida , Bigelow Carolyn , James Luther St. , Smith Wally R. , Galacteros Frederic , Kutlar Abdullah , Hull James H. , Stocker Jonathan W. ,   for the ICA‐17043‐10 Study Investigators
Published: February 2011

SummaryRed blood cell (RBC) hydration is regulated in part by the Ca2+‐activated K+ efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo‐controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty‐five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.
Red cell alloimmunization in a diverse population of transfused patients with thalassaemia
Authors: Thompson Alexis A. , Cunningham Melody J. , Singer Sylvia T. , Neufeld Ellis J. , Vichinsky Elliott , Yamashita Robert , Giardina Patricia , Kim Hae‐Young , Trachtenberg Felicia , Kwiatkowski Janet L. ,   for the Thalassemia Clinical Research Network Investigators
Published: February 2011

SummaryRed blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre‐storage screening has resulted in decreased transfusion‐transmitted infections, but anti‐RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions. Allo‐ and autoantibody rates were compared with respect to splenectomy status, ethnicity, diagnosis, duration of transfusions, treatment centre, and age at transfusion initiation, together with rates before and after 1990, when leucoreduction methods were routine at thalassaemia treatment centres. Allo‐ and autoantibodies were reported in 115 (16·5%) and 34 (4·9%) subjects, respectively. Splenectomized patients were more likely to have alloantibodies [odds ratio (OR) = 2·528, P ≤ 0·0001], or autoantibodies (OR = 2·590, P = 0·0133). Alloantibodies occurred in 19 of 91 (21%) splenectomized subjects who started transfusion after 1990, and only 18 of 233 (7·7%) nonsplenectomized subjects (P < 0·001). Data from this study demonstrate that RBC antibodies continue to develop in chronically transfused thalassaemia patients at a high rate. Splenectomy preceded the development of antibodies in most cases. Increased rates of RBC sensitization among splenectomized patients is concerning and deserves further study.
The impacts and implications of an intensifying fire regime on Alaskan boreal forest composition and albedo
Authors: BECK PIETER S. A. , GOETZ SCOTT J. , MACK MICHELLE C. , ALEXANDER HEATHER D. , JIN YUFANG , RANDERSON JAMES T. , LORANTY M. M. 
Published: February 2011

AbstractClimate warming and drying are modifying the fire dynamics of many boreal forests, moving them towards a regime with a higher frequency of extreme fire years characterized by large burns of high severity. Plot‐scale studies indicate that increased burn severity favors the recruitment of deciduous trees in the initial years following fire. Consequently, a set of biophysical effects of burn severity on postfire boreal successional trajectories at decadal timescales have been hypothesized. Prominent among these are a greater cover of deciduous tree species in intermediately aged stands after more severe burning, with associated implications for carbon and energy balances. Here we investigate whether the current vegetation composition of interior Alaska supports this hypothesis. A chronosequence of six decades of vegetation regrowth following fire was created using a database of burn scars, an existing forest biomass map, and maps of albedo and the deciduous fraction of vegetation that we derived from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery. The deciduous fraction map depicted the proportion of aboveground biomass in deciduous vegetation, derived using a RandomForest algorithm trained with field data sets (n=69, 71% variance explained). Analysis of the difference Normalized Burn Ratio, a remotely sensed index commonly used as an indicator of burn severity, indicated that burn size and ignition date can provide a proxy of burn severity for historical fires. LIDAR remote sensing and a bioclimatic model of evergreen forest distribution were used to further refine the stratification of the current landscape by burn severity. Our results show that since the 1950s, more severely burned areas in interior Alaska have produced a vegetation cohort that is characterized by greater deciduous biomass. We discuss the importance of this shift in vegetation composition due to climate‐induced changes in fire severity for carbon sequestration in forest biomass and surface reflectance (albedo), among other feedbacks to climate.
Nurses’ and midwives’ clinical leadership development needs: A mixed methods study
Authors: Casey Mary , McNamara Martin , Fealy Gerard , Geraghty Ruth 
Published: February 2011

casey m., mcnamara m., fealy g. & geraghty r. (2011) Nurses’ and midwives’ clinical leadership development needs: a mixed methods study. Journal of Advanced Nursing67(7), 1502–1513.AbstractAim. This paper is a report of a descriptive study of nurses’ and midwives’ clinical leadership development needs.Background. Nurses and midwives are expected to fulfil a leadership role at all levels, yet efforts to strategically support them are often unfocused. An analysis of clinical leadership development needs can provide the foundation for leadership initiatives to support staff.Method. A mixed methods design was used. A questionnaire was sent to 911 nurses and midwives and 22 focus groups comprising 184 participants were conducted. Data were collected between March and June 2009 across all promotional grades of nurses and midwives in Ireland. Repeated measures anova with Greenhouse–Geisser adjustment was used for post hoc pair wise comparisons of the subscale dimensions of clinical leadership. anova with Tukey’s post hoc method was used for comparison between grades on each individual subscale. Thematic analysis was undertaken on the focus group data.Results. Results reveal that needs related to development of the profession were the highest for all grades. The staff grade expressed a higher need in relation to ‘managing clinical area’, ‘managing the patient care’ and ‘skills for clinical leadership’ than managers. Qualitative analysis yielded five themes; (1) clinical leadership and leaders from a nursing and midwifery perspective; (2) quality service from a nursing and midwifery perspective; (3) clinical leaders’ roles and functions; (4) capital and (5) competences for clinical leaders and leadership and the context of clinical leadership.Conclusion. Clinical leadership concerns quality, safety and effectiveness. Nurses and midwives are ideally placed to offer the clinical leadership that is required to ensure these patient care outcomes. Development initiatives must address the leader and leadership competencies to support staff.
Oral glucose for pain relief during eye examinations for retinopathy of prematurity
Authors: Olsson Emma , Eriksson Mats 
Published: February 2011

Aim.  The aim of this study was to determine whether oral glucose could have a pain‐relieving effect during the eye examinations that premature neonates undergo in the screening for retinopathy of prematurity.Background.  Studies have shown that orally administered sweet‐tasting solutions reduce signs of pain during painful procedures such as venepuncture and heel sticks on premature and full‐term infants. This effect has not yet been proven during the eye examinations for the screening of retinopathy of prematurity.Design.  Randomised, controlled, double‐blind study.Method.  Thirty infants born before 32 weeks of gestation and/or weighing <1500 g at birth were randomised to receive 1 ml of either 30% glucose or sterile water before the eye examination. Examinations were videotaped, and the observer was blinded to the intervention. Pain responses were scored using the premature infant pain profile. Heart rate and crying time were also recorded.Results.  There were no statistically significant differences between the two groups, neither in premature infant pain profile score, heart rate changes nor crying time.Conclusion.  This study does not support the pain‐relieving effect of orally administered glucose during eye examinations in preterm infants.Relevance to clinical practice.  Oral glucose should not be used as single measure for pain relief during eye examinations of preterm infants. Other comforting and pain‐relieving measures should be used.
Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta): a pharmacokinetic study
Authors: BAKKER J. , THUESEN L. R. , BRASKAMP G. , SKAANILD M. T. , OUWERLING B. , LANGERMANS J. A. M. , BERTELSEN M. F. 
Published: February 2011

Bakker, J., Thuesen, L. R., Braskamp, G., Skaanild, M. T., Ouwerling, B., Langermans, J. A. M., Bertelsen, M. F. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta): a pharmacokinetic study. J. vet. Pharmacol. Therap.34, 464–468.Cefovecin is a third‐generation cephalosporin approved for antibacterial treatment with a 14‐day dosing interval in dogs and cats. This antibiotic may also be useful for zoo and wildlife veterinary medicine, because of its broad spectrum and long duration of activity. The aim of the study was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean maximum plasma concentration (Cmax) of cefovecin was 78 μg/mL and was achieved after 57 min. The mean apparent long elimination half‐life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 μg/mL. The PK of cefovecin in rhesus monkeys is substantially different than for dogs and cats. Cefovecin rapidly reached Cmax which however was lower than most of the MIC levels and with a very short t½. Therefore, cefovecin is not recommended for treating skin wounds in rhesus monkeys.
Can piperonyl butoxide enhance the efficacy of pyrethroids against pyrethroid‐resistant Aedes aegypti?
Authors: Bingham Georgina , Strode Clare , Tran Lien , Khoa Pham Thi , Jamet Helen Pates 
Published: February 2011

SummaryBackground  Pyrethroid resistance can be considered the main threat to the continued control of many mosquito vectors of disease. Piperonyl butoxide (PBO) has been used as a synergist to help increase the efficacy of certain insecticides. This enhancement stems from its ability to inhibit two major metabolic enzyme systems, P450s and non‐specific esterases, and to enhance cuticular penetration of the insecticide.Objective  To compare the mortality of a characterized resistant Aedes aegypti strain, Nha Trang, from Vietnam and the susceptible laboratory strain Bora Bora on netting with the pyrethroid deltamethrin (DM) alone and in combination with PBO.Methods  Resistance mechanisms were characterized using molecular and bioassay techniques; standard PCR was used to test for the kdr target site mutation. Potential genes conferring metabolic resistance to DM were identified with microarray analysis using the Ae. aegypti‘detox chip’. These data were analysed alongside results from WHO susceptibility tests. P450, CYP9J32, was significantly overexpressed in the DM‐resistant strain compared with the susceptible Bora Bora strain. Another five genes involved with oxidative stress responses in mosquitoes were also significantly overexpressed. The Nha Trang strain was homozygous for two kdr mutations. WHO cone bioassays were used to investigate mortality with incorporated DM‐treated nets with and without PBO. PBO used in combination with DM resulted in higher mortality than DM alone.Conclusion  Synergists may have an important role to play in the future design of vector control products in an era when alternatives to pyrethroids are scarce.
Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co‐segregates with tuberous sclerosis complex in mildly affected kindreds
Authors: Wentink M , Nellist M , Hoogeveen‐Westerveld M , Zonnenberg B , van der Kolk D , van Essen T , Park S‐M , Woods G , Cohn‐Hokke P , Brussel W , Smeets E , Brooks A , Halley D , van den Ouweland A , Maat‐Kievit A 
Published: February 2011

Wentink M, Nellist M, Hoogeveen‐Westerveld M, Zonnenberg B, van der Kolk D, van Essen T, Park S‐M, Woods G, Cohn‐Hokke P, Brussel W, Smeets E, Brooks A, Halley D, van den Ouweland A, Maat‐Kievit A. Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co‐segregates with tuberous sclerosis complex in mildly affected kindreds.Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1–TSC2 function. Interestingly however, in each case, the TSC1–TSC2 interaction was not affected by the amino acid substitution.
Training of trainers on epinephrine autoinjector use
Authors: Arga Mustafa , Bakirtas Arzu , Catal Ferhat , Derinoz Oksan , Harmanci Koray , Razi Cem H. , Ergöcen Salih , Demirsoy M. Sadik , Turktas Ipek 
Published: February 2011

To cite this article: Arga M, Bakirtas A, Catal F, Derinoz O, Harmanci K, Razi CH, Ergöcen S, Demirsoy MS, Turktas I. Training of trainers on epinephrine autoinjector use. Pediatric Allergy Immunology 2011; 22: 590–593.AbstractThe majority of physicians do not know how to use epinephrine autoinjectors. This displays that current education of physicians on anaphylaxis is inadequate for a thorough practice. We hypothesize that a theoretical lecture together with a practical session on epinephrine autoinjector use will improve its proper use by physicians. Residents, specialists, and consultants from General Pediatrics excluding allergists and allergy fellows were included in this study. All physicians were given an eight‐item questionnaire followed by a practical session scoring and timing ability to use epinephrine autoinjector trainer. This ensued with one‐to‐one hands‐on training on correct autoinjector use. Finally, a joint theoretical lecture on anaphylaxis including re‐demonstration of epinephrine autoinjector use was given. All physicians were scored a second time on use of epinephrine autoinjector 6 months later. One hundred fifty‐one of 196 participants completed all steps of the study in four tertiary hospitals. Correct use of epinephrine autoinjector improved from 23.3% to 74.2%, mean score from 3.49 ± 1.14 to 4.66 ± 0.65, need for prospectus from 91.4% to 29.1%, and mean time to administer autoinjector from 28.01 ± 6.22 s to 19.62 ± 5.01 s (p < 0.001 for each). The rate of most common mistakes during autoinjector use decreased but the ranking did not change. An integrated theoretical and practical education increased correct of epinephrine autoinjector use by physicians. Ongoing mistakes despite this education may be related with its design.
Stochastic simulation of dairy cattle breeding schemes: Genetic evaluation of nucleus size and type
Authors: Schrooten C. , van Arendonk J. A. M. 
Published: February 2011

SummaryA stochastic model was developed for the simulation of dairy cattle breeding programmes including use of embryo transfer and nucleus schemes. All bulls in the model were simulated individually. In order to reduce the computational demands only nucleus and top population cows were simulated individually while the commercial cow population was simulated by age groups with a deterministic model. Selection was for a single sex‐limited trait with a heritability of 0.25 and based on animal model breeding value estimates. Selection of dams was across age classes while sires were required to have a progeny test before they could be selected as proven bull or bull sire. The first 15 years of the simulated period was used to reach a population with an equilibrium genetic progress for a progeny testing scheme. Comparisons were based on the 25 year period after an alternative breeding scheme was adopted in year 15.The progeny testing scheme without MOET resulted in an annual genetic progress of .234 σA. The annual genetic response in open MOET nucleus schemes with 120 and 240 replacement heifers per year was 4.3% and 5.6% higher, respectively, than in the progeny testing scheme. The response was reduced by 1.7% and 0.9% when the nucleus schemes with 120 and 240 replacements heifers per year were closed.ZusammenfassungStochastische Simulation von Milchviehzuchtplänen: Genetische Bewertung von Nukleusgröße und TypEin stochastisches Modell wurde für die Simulation eines Zuchtprogrammes mit Embryotransfer und Nukleus entwickelt. Alle Bullen wurden im Modell individuell simuliert. Um die Rechenansprüche zu begrenzen, wurden nur Nukleus‐ und Spitzenpopulationskühe individuell simuliert, während die kommerzielle Kuhpopulation deterministisch nach Altersgruppen simuliert wurde. Selektion betraf ein einzelnes geschlechtsgebundenes Merkmal mit einer Heritabilität von 25% und beruhte auf einem Tiermodell. Die Selektion der Muttertiere erfolgte über Altersklassen hinweg, während Vatertiere vor ihrer Selektion als geprüfte oder Elitebullen eine Nachkommenschaftsprüfung haben mußten. Die ersten 15 Jahre der simulierten Periode wurden bis zum Erreichen eines Gleichgewichtsfortschrittes des Nachkommenschaftsprüfsystems benötigt. Die Vergleiche beruhen auf der folgenden 25 Jahrperiode, nachdem im Jahr 15 ein alternatives Zuchtsystem eingeführt worden war.Nachkommenschaftsprüfschema ohne MOET resultierte in einen Jahreszuchtfortschritt von 0,234 σA. Der jährliche genetische Fortschritt im offenen MOET Nukleusschema mit 120 und 240 nachgestellten Kalbinnen pro Jahr war 4,3 bzw. 5,6% höher als beim Nachkommenschaftsprüfsystem. Der Fortschritt wurde um 1,7 bzw. 0,9% reduziert, wenn die Nukleusschema geschlossen worden sind.
Liposome mediated gene transfer via spermatozoa into avian egg cells
Authors: Rottmann O.J. , Antes R. , Höfer P. , Maierhofer G. 
Published: February 2011

SummaryLiposomes were prepared in the presence of plasmid DNA and allowed to react with spermatozoa from roosters prior to artificial insemination of 200 hens. Twelve days old fetuses developed from fertilized eggs were analysed by Southern blot technique to detect the transfer of the foreign sequences. About 26% of all fetuses examined displayed the banding pattern of the transferred plasmid. The results indicate that the sequences are not chromosomally integrated but are present in episomic form. The method described here is easy to handle so that it may become an appropriate means to establish large numbers of transgenic animals.ZusammenfassungLiposomaler Gentransfer über Spermien in HühnereierMischsperma von mehreren Hähnen wurde mit Liposomen inkubiert, in denen Plasmid‐DNA eingeschlossen war. Mit diesem Sperma sind 200 Hennen inseminiert worden. Nach 12 Tagen Bebrütung wurden die Föten mittels Southernblot‐Technik analysiert. Rund 26% aller untersuchten Föten zeigten die typischen Bandenmuster des transferierten Plasmids. Die Befunde weisen darauf hin, daß das Plasmid nicht chromosomal integriert, sondern als Episom neben der genomischen DNA vorliegt. Das hier beschriebene Gentransfer‐Verfahren ist einfach zu handhaben, so daß ohne nennenswerten Aufwand größere Zahlen transgener Tiere erstellt werden können.