bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis
Authors: Vennegoor Anke , Rispens Theo , Strijbis Eva MM , Seewann Alexandra , Uitdehaag Bernard MJ , Balk Lisanne J , Barkhof Frederik , Polman Chris H , Wolbink Gertjan , Killestein Joep 
Published: September 2012

Background: Antibodies against natalizumab have been found in 4.5–14.1% of natalizumab-treated multiple sclerosis (MS) patients. If antibodies persist, they are associated with an adverse effect on treatment response. However, it has proved to be difficult to standardize anti-drug antibody measurements. Objectives: The purpose of this study was to evaluate the clinical and radiological impact of serum natalizumab concentrations and their relation with anti-natalizumab antibodies in MS patients. Methods: In this prospective observational cohort study of 73 consecutive patients treated with natalizumab, we measured serum natalizumab levels and antibody titers before the start of natalizumab treatment, at weeks 12 and 24 and annually after natalizumab initiation. Antibodies against natalizumab were measured by radioimmunoassay and serum natalizumab concentrations using a newly developed enzyme linked immunosorbent assay (ELISA). Magnetic resonance imaging (MRI) scan and clinical evaluation were performed before the start of natalizumab treatment and subsequently every year. Results: Antibodies were detected in 58% of the natalizumab-treated patients. All patients developed their antibodies before week 24. The large majority of these patients reverted to neutralizing antibody (NAb) negative status during follow-up. The presence of antibodies was inversely correlated with serum natalizumab concentration ( p<0.001). Only high antibody titers are associated with very low or undetectable serum natalizumab concentration. Both high antibody titers and low serum natalizumab concentrations are associated with relapses and gadolinium-enhancing lesions on MRI. Conclusions: Our data show that both low natalizumab serum concentration and high antibody titers are associated with a lack of efficacy of natalizumab. Measuring serum natalizumab, using a highly specific assay, might lead to more enhanced precision using natalizumab in individual patients.
Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells
Authors: Tewalt Eric F. , Cohen Jarish N. , Rouhani Sherin J. , Guidi Cynthia J. , Qiao Hui , Fahl Shawn P. , Conaway Mark R. , Bender Timothy P. , Tung Kenneth S. , Vella Anthony T. , Adler Adam J. , Chen Lieping , Engelhard Victor H. 
Published: September 2012

Abstract
Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to CD8 T cells (TCD8). We demonstrate that LECs mediate deletion only via programmed cell death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B- and T-lymphocyte attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation and proliferation of TCD8, but lack of costimulation through 4-1BB leads to rapid high-level expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that is necessary for TCD8 survival. Rescue of tyrosinase-specific TCD8 by interference with PD-1 or provision of costimulation results in autoimmune vitiligo, demonstrating that LECs are significant, albeit suboptimal, antigen-presenting cells. Because LECs express numerous peripheral tissue antigens, lack of costimulation coupled to rapid high-level up-regulation of inhibitory receptors may be generally important in systemic peripheral tolerance.
Combinatorial control of temporal gene expression in the Drosophila wing by enhancers and core promoters
Authors: O’Keefe David D , Thomas Sean R , Bolin Kelsey , Griggs Ellen , Edgar Bruce A , Buttitta Laura A 
Published: September 2012

Abstract

Background
The transformation of a developing epithelium into an adult structure is a complex process, which often involves coordinated changes in cell proliferation, metabolism, adhesion, and shape. To identify genetic mechanisms that control epithelial differentiation, we analyzed the temporal patterns of gene expression during metamorphosis of the Drosophila wing.

Results
We found that a striking number of genes, approximately 50% of the Drosophila transcriptome, exhibited changes in expression during a time course of wing development. While cis-acting enhancer sequences clearly correlated with these changes, a stronger correlation was discovered between core-promoter types and the dynamic patterns of gene expression within this differentiating tissue. In support of the hypothesis that core-promoter type influences the dynamics of expression, expression levels of several TATA-box binding protein associated factors (TAFs) and other core promoter-associated components changed during this developmental time course, and a testes-specific TAF (tTAF) played a critical role in timing cellular differentiation within the wing.

Conclusions
Our results suggest that the combinatorial control of gene expression via cis-acting enhancer sequences and core-promoter types, determine the complex changes in gene expression that drive morphogenesis and terminal differentiation of the Drosophila wing epithelium.
“Looking back to my family”: Indigenous Australian patients’ experience of hemodialysis
Authors: Anderson Kate , Cunningham Joan , Devitt Jeannie , Preece Cilla , Cass Alan 
Published: September 2012

Abstract

Background
In common with Indigenous populations elsewhere, Indigenous Australians have higher incidence of end-stage kidney disease (ESKD), but lower transplantation rates than their non-Indigenous counterparts. Understanding how the demands of dialysis impact on, and are impacted by, the lives of Indigenous patients may provide important insight into treatment pathways and decision-making.

Methods
We conducted semi-structured interviews in 2005–06 with 146 Indigenous and 95 non-Indigenous patients from nine hospital renal wards and 17 associated dialysis centres, which together treat the majority of Indigenous Australian ESKD patients.

Results
Factors influencing treatment experience included: the impacts of late diagnosis; family separations associated with relocating for treatment; the physical and psychosocial demands of hemodialysis; and ineffective communication between health care providers and patients. Although not unique to them, Indigenous patients were more likely to experience the combined effect of all factors.

Conclusions
Social/situational circumstances profoundly affect Indigenous Australian dialysis patients’ ability to fully engage with treatment. This may ultimately affect their likelihood of receiving optimal treatment, including transplantation. Areas for improvement include: earlier diagnosis; improved linkages between specialist renal services and primary care in regional settings; more effective communication and patient education; and more systematic, transparent approaches to patient “compliance” in transplant and home dialysis guidelines.
Probable levetiracetam-related serum alkaline phosphatase elevation
Authors: Xiong Nian , Hou Lingling , Lu Na , Mohamed Asrah A , Wang Tao , Huang Yaling 
Published: September 2012

Abstract

Background
Levetiracetam (LEV) is an antiepileptic drug with a favorable tolerability and safety profile with little or no effect on liver function.

Case presentation
Here, we reported an epileptic pediatric patient who developed a significant elevation in serum alkaline phosphatase level (ALP) during LEV monotherapy. Moreover, the serum ALP level was surprisingly decreased to normal after LEV discontinuation. The Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating firstly LEV was a probable cause for the increased serum ALP.

Conclusions
Cautious usage and concerns of the LEV-associated potential ALP elevation should be considered when levetiracetam is prescribed to epilepsy patients, especially pediatric patients.
A cost-effective method for Illumina small RNA-Seq library preparation using T4 RNA ligase 1 adenylated adapters
Authors: Chen Yun-Ru , Zheng Yi , Liu Bao , Zhong Silin , Giovannoni Jim , Fei Zhangjun 
Published: September 2012

Abstract

Background
Deep sequencing is a powerful tool for novel small RNA discovery. Illumina small RNA sequencing library preparation requires a pre-adenylated 3’ end adapter containing a 5’,5’-adenyl pyrophosphoryl moiety. In the absence of ATP, this adapter can be ligated to the 3’ hydroxyl group of small RNA, while RNA self-ligation and concatenation are repressed. Pre-adenylated adapters are one of the most essential and costly components required for library preparation, and few are commercially available.

Results
We demonstrate that DNA oligo with 5’ phosphate and 3’ amine groups can be enzymatically adenylated by T4 RNA ligase 1 to generate customized pre-adenylated adapters. We have constructed and sequenced a small RNA library for tomato (Solanum lycopersicum) using the T4 RNA ligase 1 adenylated adapter.

Conclusion
We provide an efficient and low-cost method for small RNA sequencing library preparation, which takes two days to complete and costs around $20 per library. This protocol has been tested in several plant species for small RNA sequencing including sweet potato, pepper, watermelon, and cowpea, and could be readily applied to any RNA samples.
Direct Activation of Xenopus Iodotyrosine Deiodinase by Thyroid Hormone Receptor in the Remodeling Intestine during Amphibian Metamorphosis
Authors: Fujimoto Kenta , Matsuura Kazuo , Das Biswajit , Fu Liezhen , Shi Yun-Bo 
Published: September 2012

AbstractThyroid hormone (TH) plays critical roles during vertebrate postembryonic development. TH production in the thyroid involves incorporating inorganic iodide into thyroglobulin. The expression of iodotyrosine deiodinase (IYD; also known as iodotyrosine dehalogenase 1) in the thyroid gland ensures efficient recycling of iodine from the byproducts of TH biosynthesis: 3′-monoiodotyrosine and 3′, 5′-diiodotyrosine. Interestingly, IYD is known to be expressed in other organs in adult mammals, suggesting iodine recycling outside the thyroid. On the other hand, the developmental role of iodine recycling has yet to be investigated. Here, using intestinal metamorphosis as a model, we discovered that the Xenopus tropicalis IYD gene is strongly up-regulated by TH during metamorphosis in the intestine but not the tail. We further demonstrated that this induction was one of the earliest events during intestinal metamorphosis, with IYD being activated directly through the binding of liganded TH receptors to a TH response element in the IYD promoter region. Because iodide is mainly taken up from the diet in the intestine and the tadpole stops feeding during metamorphosis when the intestine is being remodeled, our findings suggest that IYD transcription is activated by liganded TH receptors early during intestinal remodeling to ensure efficient iodine recycling at the climax of metamorphosis when highest levels of TH are needed for the proper transformations of different organs.
Divergent Roles of the CRH Receptors in the Control of Gonadotropin Secretion Induced by Acute Restraint Stress at Proestrus
Authors: Traslaviña Guillermo A. Ariza , Franci Celso Rodrigues 
Published: September 2012

AbstractCRH has been implicated as a mediator of stress-induced effects on the hypothalamus-pituitary-gonad axis, acting via CRH receptors in various brain regions. We investigated whether the effects of restraint stress on the secretion of gonadotropins on the morning of proestrus are mediated by the CRH-R1 or CRH-R2 receptors in the oval subdivision of the anterolateral BST, the central amygdala, the locus coeruleus (LC), or the A1 and A2 neuron groups in the medulla. At proestrus morning, rats were injected with antalarmin (a CRH-R1 antagonist), asstressin2-B (a CRH-R2 antagonist) or vehicles. Thirty minutes after the injection, the animals were placed into restraints for 30 min, and blood was sampled for 2 h. At the end of the experiment, the brains were removed for immunofluorescence analyses. Restraint stress increased the levels of FSH and LH. Antalarmin blocked the stress-induced increases in FSH and LH secretion, but astressin2-B only blocked the increase in FSH secretion. LC showed intense stress-induced neuronal activity. FOS/tyrosine-hydroxylase coexpression in LC was reduced by antalarmin, but not astressin2-B. The CRH-R1 receptor, more than CRH-R2 receptor, appears to be essential for the stimulation of the hypothalamus-pituitary-gonad axis by acute stress; this response is likely mediated in part by noradrenergic neurons in the LC. We postulate that the stress-induced facilitation of reproductive function is mediated, at least in part, by CRH action through CRH-R1 on noradrenaline neurons residing in the LC that trigger GnRH discharge and gonadotropin secretion.
Deficiency of Angiotensin Type 1a Receptors in Adipocytes Reduces Differentiation and Promotes Hypertrophy of Adipocytes in Lean Mice
Authors: Putnam Kelly , Batifoulier-Yiannikouris Frederique , Bharadwaj Kalyani G. , Lewis Eboni , Karounos Michael , Daugherty Alan , Cassis Lisa A. 
Published: September 2012

AbstractAdipocytes express angiotensin receptors, but the direct effects of angiotensin II (AngII) stimulating this cell type are undefined. Adipocytes express angiotensin type 1a receptor (AT1aR) and AT2R, both of which have been implicated in obesity. In this study, we determined the effects of adipocyte AT1aR deficiency on adipocyte differentiation and the development of obesity in mice fed low-fat (LF) or high-fat (HF) diets. Mice expressing Cre recombinase under the control of the aP2 promoter were bred with AT1aR-floxed mice to generate mice with adipocyte AT1aR deficiency (AT1aRaP2). AT1aR mRNA abundance was reduced significantly in both white and brown adipose tissue from AT1aRaP2 mice compared with nontransgenic littermates (AT1aRfl/fl). Adipocyte AT1aR deficiency did not influence body weight, glucose tolerance, or blood pressure in mice fed either LF or high-fat diets. However, LF-fed AT1aRaP2 mice exhibited striking adipocyte hypertrophy even though total fat mass was not different between genotypes. Stromal vascular cells from AT1aRaP2 mice differentiated to a lesser extent to adipocytes compared with controls. Conversely, incubation of 3T3-L1 adipocytes with AngII increased Oil Red O staining and increased mRNA abundance of peroxisome proliferator-activated receptor γ (PPARγ) via AT1R stimulation. These results suggest that reductions in adipocyte differentiation in LF-fed AT1aRaP2 mice resulted in increased lipid storage and hypertrophy of remaining adipocytes. These results demonstrate that AngII regulates adipocyte differentiation and morphology through the adipocyte AT1aR in lean mice.
Intraflagellar transport proteins cycle between the flagellum and its base
Authors: Buisson Johanna , Chenouard Nicolas , Lagache Thibault , Blisnick Thierry , Olivo-Marin Jean-Christophe , Bastin Philippe 
Published: September 2012

Summary
Intraflagellar transport (IFT) is necessary for the construction of cilia and flagella. IFT proteins are concentrated at the base of the flagellum but little is known about the actual role of this pool of proteins. Here, IFT was investigated in Trypanosoma brucei, an attractive model for flagellum studies, using GFP fusions with IFT52 or the IFT dynein heavy chain DHC2.1. Tracking analysis by a curvelet method allowing automated separation of forward and return transport demonstrated a uniform speed for retrograde IFT (5 µm s−1) but two distinct populations for anterograde movement that are sensitive to temperature. When they reach the distal tip, anterograde trains are split into three and converted to retrograde trains. When a fast anterograde train catches up with a slow one, it is almost twice as likely to fuse with it rather than to overtake it, implying that these trains travel on a restricted set of microtubules. Using photobleaching experiments, we show for the first time that IFT proteins coming back from the flagellum are mixed with those present at the flagellum base and can reiterate a full IFT cycle in the flagellum. This recycling is dependent on flagellum length and IFT velocities. Mathematical modelling integrating all parameters actually reveals the existence of two pools of IFT proteins at the flagellum base, but only one is actively engaged in IFT.
An effective method for terrestrial arthropod euthanasia
Authors: Bennie Neil A.C. , Loaring Christopher D. , Bennie Mikaella M.G. , Trim Steven A. 
Published: September 2012

Summary
As scientific understanding of invertebrate life increases so does the concern for how to end that life in a way that not only minimises (potential) suffering and is non-recoverable, but is also safe for those carrying out the procedure. There is increasing debate on the most appropriate euthanasia methods for invertebrates as their use in experimental research and zoological institutions grows. Their popularity as pet species has also lead to an increase in the need for greater veterinary understanding. Through the use of a local injection of potassium chloride (KCl) initially developed for use in American lobsters, this manuscript describes a safe and effective method for euthanasia in terrestrial invertebrates. Initial work focused on empirically determining the dose for cockroaches then extrapolating to other arthropod species. For this method of euthanasia, we propose the term 'targeted hyperkalosis' to describe death through terminal depolarisation of the thoracic ganglia as a result of high potassium concentration.
Candidate Socioemotional Remediation Program for Individuals with Intellectual Disability
Authors: Glaser Bronwyn , Lothe Amelie , Chabloz Mélanie , Dukes Daniel , Pasca Catherine , Redoute Jérôme , Eliez Stephan 
Published: September 2012

Abstract
The authors developed a computerized program, Vis-à-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and Understanding, and Working Memory. Ten children with idiopathic developmental delay completed four 20-min weekly sessions of VAV for 12 weeks with an adult. Participants were evaluated before (Time 0) and after (Time 1) training and 6 months after remediation (Time 2). Subjects improved on all three modules during training and on emotion recognition and nonverbal reasoning post-VAV. These gains were still present at Time 2. VAV is a promising new tool for working on socioemotional impairments in hard-to-treat pediatric populations.
Using Response-prompting Procedures During Small-group Direct Instruction: Outcomes and Procedural Variations
Authors: Ledford Jennifer R. , Lane Justin D. , Elam Katherine L. , Wolery Mark 
Published: September 2012

Abstract
Research was reviewed on small-group instruction for learners with disabilities. The review was conducted for articles published between 1990 and 2010 on the application of small-group direct instruction to teach discrete skills using prompting procedures. A total of 47 articles with 197 participants and 687 replications of effects was located. Small-group instruction was effective for 195 of 197 participants and across variations in implementation and contexts. Implementers were primarily special education personnel, and instruction typically occurred in special education settings. Rigorous designs were used in all studies, and fidelity was assessed in 46 of 47 studies and was uniformly high. Students consistently reached criterion on their own target behaviors, generalized those behaviors, maintained them, and learned the behaviors taught to their peers (when this was measured, which occurred in a majority of the studies). Future research should examine comparisons of procedural variables and promoting social behaviors between group mates.
Physical Properties of Whole Rye Seed (Secale cereal)
Authors: Jouki Mohammad , Emam-Djomeh Zahra , Khazaei Naimeh 
Published: September 2012

Abstract
Certain physical properties of rye – density, true density, angle of internal friction, porosity and static coefficient of friction – are necessary for the design of transport, storage and processing equipment. . These properties were evaluated as a function of moisture content of grain. The grain was tested for bulk density, density, porosity, angle of internal friction and coefficient of friction with various materials at 9% and 13% moisture content (dry basis, db). The average length, width and thickness of the rye grains were 7.11mm, 4.65mm and 3.18mm. It was observed that bulk density decreased linearly from 598.41 to 580.76 kg/m3, as moisture content increased, while density increased linearly from 922.43 to 991.56 kg/m3. The porosity and angle of internal friction increased as moisture increased. The porosity increased linearly from 37.00% to 40.50%, and the angle of internal friction increased from 21.500 to 25.000. The static coefficient of friction increased from 0.283 to 0.412, 0.345 to 0.438, and 0.380 to 0.461 for glass, galvanized iron and wood surfaces respectively.
Physicochemical and colour properties of organic and conventional kiwifruits as affected by storage periods
Authors: Islam Ali , Altuntas Ebubekir , Cangi Rustem , Kaya Cemal , Yildiz Aylin 
Published: September 2012

Abstract
In this study, the effect of storage periods (0, 2, 3 and 4 months) on physico-chemical and colour properties of organic and conventional kiwifruits were investigated. The fruit mass, geometric mean diameter, volume of organic and conventional kiwifruits decreased with increasing storage period. The skin and flesh firmnesses were higher in organic kiwifruits than that of conventional kiwifruits. The organic acid contents was higher in conventional kiwifruits than that of organic kiwifruits; the sugar contents was higher in organic kiwifruits than that of conventional kiwifruits. Colour characteristics (L*, a*, b*) for skin fruit and fruit juice in organic and conventional kiwifruits were higher in conventional kiwifruits than that of organic kiwifruits. Results from this study showed that the physico-chemical properties and colour characteristics of organic and conventional kiwifruits were affected by storage periods.
Study on the solidification kinetics of high-density polyethylene during thin-walled injection molding process
Authors: Deng Shuang-quan , Yang Bin , Miao Ji-bin , Xia Ru , Qian Jia-sheng , Chen Peng , Yang Ming-bo 
Published: September 2012

Abstract
In this work, the effect of the initial and secondary temperature differences on the solidification behaviors of high-density polyethylene (HDPE) during the thin-walled injection molding (TWIM) was intensively investigated. Simulated temperature profiles using the enthalpy transformation methodology were compared with an in situ temperature measurement, and reasonable agreement was achieved between calculations and measurements. Two-dimensional wide-angle X-ray diffraction characterization shows that the formation of oriented crystal structures was considerably affected by the thermal gradient within the injection-molded article. The present study can be practically significant to the optimization of the cooling parameters during the TWIM of crystalline polymers as well as to the further study on the relationship among “processing-structure-property” of polymeric materials.