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#32746466   2020/08/03 To Up

Population Pharmacokinetic Modeling of von Willebrand Factor Activity in von Willebrand Disease Patients after Desmopressin Administration.

 Most von Willebrand disease (VWD) patients can be treated with desmopressin during bleeding or surgery. Large interpatient variability is observed in von Willebrand factor (VWF) activity levels after desmopressin administration. The aim of this study was to develop a pharmacokinetic (PK) model to describe, quantify, and explain this variability.
Nico C B de Jager, Jessica M Heijdra, Quincy Kieboom, Marieke J H A Kruip, Frank W G Leebeek, Marjon H Cnossen, Ron A A Mathôt,

2570 related Products with: Population Pharmacokinetic Modeling of von Willebrand Factor Activity in von Willebrand Disease Patients after Desmopressin Administration.

100μg100μg100μg96 tests100 μg48 assays 100 ug0.1 mg500 tests96T1

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#32745983   2020/07/04 To Up

High-Dimensional Design-Of-Experiments Extracts Small-Molecule-Only Induction Conditions for Dorsal Pancreatic Endoderm from Pluripotency.

The derivation of endoderm and descendant organs, such as pancreas, liver, and intestine, impacts disease modeling and regenerative medicine. Use of TGF-β signaling agonism is a common method for induction of definitive endoderm from pluripotency. By using a data-driven, High-Dimensional Design of Experiments (HD-DoE)-based methodology to address multifactorial problems in directed differentiation, we found instead that optimal conditions demanded BMP antagonism and retinoid input leading to induction of dorsal foregut endoderm (DFE). We demonstrate that pancreatic identity can be rapidly, and robustly, induced from DFE and that such cells are of dorsal pancreatic identity. The DFE population was highly competent to differentiate into both stomach organoids and pancreatic tissue types and able to generate fetal-type β cells through two subsequent differentiation steps using only small molecules. This alternative, rapid, and low-cost basis for generating pancreatic insulin-producing cells may have impact for the development of cell-based therapies for diabetes.
Michael A Bukys, Alexander Mihas, Krystal Finney, Katie Sears, Divya Trivedi, Yong Wang, Jose Oberholzer, Jan Jensen

2763 related Products with: High-Dimensional Design-Of-Experiments Extracts Small-Molecule-Only Induction Conditions for Dorsal Pancreatic Endoderm from Pluripotency.

1001100ug Lyophilized10 ml

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#32745910   2020/07/31 To Up

Role of EFNA1 in tumorigenesis and prospects for cancer therapy.

Cancer is one of the major threats to human health. It is of vital importance to reveal the mechanisms of tumorigenesis, identify effective biomarkers and develop novel treatments to improve patient outcome. EFNA1 (ephrinA1) is a member of the EFN family, and it has been studied extensively since its discovery in 1990. Increasing evidence indicates that EFNA1 plays a pivotal role in the pathogenesis of tumors. We provide a detailed overview of the expression and prognostic value of EFNA1 in different types of human malignancies. We briefly discuss the mechanisms of EFNA1 induction in hypoxic environments and its pro-angiogenic function in different cancer cells. We describe the effects of EFNA1 on tumor growth, invasiveness and metastasis. We summarize recent advances in EFNA1-associated cancer therapeutics with emphasis on the prospect of novel anti-tumor methods based on EFNA1.
Yongping Hao, Guang Li

2307 related Products with: Role of EFNA1 in tumorigenesis and prospects for cancer therapy.



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#32745810   2020/07/31 To Up

Comparative analysis of mitochondrial DNA datasets indicates that Cylicostephanus minutus represents a species complex.

Cyathostomins are one kind of the most important parasites in equids. Cylicostephanus minutus is a member of the subfamily Cyathostominae. In the present study, we determined the complete mitochondrial (mt) genomes from four Cs. minutus isolates and reconstructed the phylogenetic relationship of Strongylidae to test the hypothesis that Cs. minutus represents a species complex. The complete mt genome sequences of Cs. minutus were 13,772-13,822 bp in length, and contained 36 genes (12 protein coding genes, 22 tRNA genes, two rRNA genes), and two non-coding regions (NCRs). The intraspecific identity of nucleotide sequences and amino acid sequences in Cs. minutus (1-4) were 89.3-97.9% and 97.0-98.8%, respectively. Two operational taxonomic units (OTUs) were determined based on the mt genome sequences, OTU 2 (Csm 1 and Csm 2) and OTU 3 (Csm 3 and Csm 4). Sequence analysis showed the divergence between OTU 2 and OTU 3 was 8.9-10.7%. Pairwise comparisons of 12 protein coding genes between OTU 2 and OTU 3 showed a difference of 3.0-13.3% at the nucleotide level and 0-6.7% at the amino acid level. Phylogenetic analysis showed the separation of Cs. minutus isolates from the same host into different distinct clades based on mt genomes. Comparisons of partial mt cox1, nad5, and cytb and ITS2 sequences from 20 Cs. minutus isolates from the same host and the same geographical location with other Cs. minutus sequences available in GenBank revealed significant nucleotide differences. Phylogenetic analysis showed a separation of Cs. minutus into three distinct clades. Thus, the comparative and phylogenetic analyses of mtDNA datasets indicated that Cs. minutus represents a complex of at least three species. Our results have further confirmed the existence of a cryptic Cs. minutus species, and provides a reference for the taxonomical, population genetics, and systematics studies of other cyathostomin species.
Yuan Gao, Yang-Yuan Qiu, Xiao-Qing Meng, Xiao Yang, Zhong-Huai Zhang, Zi-Yang Diao, Shuang Wang, Chun-Ren Wang, Min-Xin Song

2065 related Products with: Comparative analysis of mitochondrial DNA datasets indicates that Cylicostephanus minutus represents a species complex.

100ul 100ul 100ul1 ml 100ul96T 100ul 100ul 100ul 100ul 100ul

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#32745760   2020/07/24 To Up

Novel HLA-A2 restricted antigenic peptide derivatives with high affinity for the treatment of breast cancer expressing NY-ESO-1.

Tumor immunotherapy based on specific tumor antigen has become the focus for breast cancer, and research into cancer/testes antigens (CTA) is progressing. As an important member in the CTA, NY-ESO-1 plays a crucial role in the treatment and prognosis of breast cancer. In this study, we aimed to improve the binding ability to MHC by designing and synthesizing stable NY-ESO-1-derived peptides, based on NetMHC 4.0 webserver (http://www.cbs.dtu.dk/services/NetMHC/) and HLP webserver (http://crdd.osdd.net/raghava/hlp/pep_both.htm). Moreover, after modification of the lead compound, affinity of the peptides to human leukocyte antigen-A2 (HLA-A2) was determined by a flow cytometry and an inverted fluorescence microscope in T2 cells that show high expression of HLA-A2. The results demonstrated that the affinity of peptides II-4 and II-10 to HLA-A2 was significantly better when compared to others (II-Lead, II-1 ~ II-3, II-5 ~ II-9, II-11 ~ II-15). Further studies indicated that II-4 and II-10, especially II-4, significantly promoted the maturation of HLA-A2-positive human peripheral blood-derived dendritic cells (DCs) from morphology and surface markers, the activation of CD8 + T lymphocytes, and the type-specific killing effect on HLA-A2/NY-ESO-1 MDA-MB-231 cells. Molecular docking studies suggested a strong interaction between peptide II-4 and HLA-A2, thereby indicating that the II-4 is a promising candidate with antigenic potential in the field of immunotherapy that needs more studies.
Wei Shi, Zhenzhen Tong, Qianqian Qiu, Na Yue, Weiwei Guo, Feng Zou, Daoguang Zhou, Jiuhui Li, Wenlong Huang, Hai Qian

2233 related Products with: Novel HLA-A2 restricted antigenic peptide derivatives with high affinity for the treatment of breast cancer expressing NY-ESO-1.



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#32745679   2020/07/31 To Up

Conduction Delays in the Visual Pathways of Progressive Multiple Sclerosis Patients Covary with Brain Structure.

In developed countries, multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. MS is a chronic demyelinating disease of the central nervous system, in which myelin is attacked, changing white matter structure and leaving lesions. The demyelination has a direct effect on white matter conductivity. This effect can be examined in the visual system, where damage is highly prevalent in MS, leading to substantial delays in conduction, commonly measured with visual evoked potentials (VEPs). The structural damage to the visual system in MS is often estimated with MRI measurements in the white matter. Recent developments in quantitative MRI (qMRI) provide improved sensitivity to myelin content and new structural methods allow better modeling of the axonal structure, leading researchers to link white matter microstructure to conduction properties of action potentials along fiber tracts. This study attempts to explain the variance in conduction latencies down the visual pathway using structural measurements of both the retina and the optic radiation (OR). Forty-eight progressive MS patients, participants in a longitudinal stem-cell therapy clinical trial, were included in this study, three and six months post final treatment. Twenty-seven patients had no history of optic neuritis, and were the main focus of this study. All participants underwent conventional MRI scans, as well as diffusion MRI and qMRI sequences to account for white matter microstructure. Optical coherence tomography scans were also obtained, and peripapillary retinal nerve fiber layer (pRNFL) thickness and macular volume measurements were extracted. Finally, latencies of recorded VEPs were estimated. Our results show that in non-optic neuritis progressive MS patients there is a relationship between the VEP latency and both retinal damage and OR lesion load. In addition, we find that qMRI values, sampled along the OR, are also correlated with VEP latency. Finally, we show that combining these parameters using PCA we can explain more than 40% of the inter-subject variance in VEP latency. In conclusion, this study contributes to understanding the relationship between the structural properties and conduction in the visual system in disease. We focus on the visual system, where the conduction latencies can be estimated, but the conclusions could be generalized to other brain systems where the white matter structure can be measured. It also highlights the importance of having multiple parameters when assessing the clinical stages of MS patients, which could have major implications for future studies of other white matter diseases.
Shai Berman, Yael Backner, Ronnie Krupnik, Friedemann Paul, Panayiota Petrou, Dimitrios Karussis, Netta Levin, Aviv A Mezer

1138 related Products with: Conduction Delays in the Visual Pathways of Progressive Multiple Sclerosis Patients Covary with Brain Structure.

96 tests

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#32745542   2020/07/31 To Up

Commercially available transfection reagents and negative control siRNA are not inert.

The transfection of synthetic small interfering (si)RNA into cultured cells forms the basis of studies that use RNA interference (commonly referred to as "gene knockdown") to study the impact of loss of gene or protein expression on a biological pathway or process. In these studies, mock transfections (with transfection reagents alone), and the use of synthetic negative control (apparently inert) siRNA are both essential negative controls. This report reveals that three widely-used transfection reagents (X-tremeGENE™, HiPerFect, and Lipofectamine® 2000) and five commercially-available control siRNA (from Ambion, Sigma, Santa Cruz, Cell Signaling Technology, and Qiagen) are not inert in cell-culture studies. Both transfection reagents and control siRNA perturbed steady-state mRNA and protein levels in primary mouse lung fibroblasts and in NIH/3T3 cells (a widely-used mouse embryonic fibroblast cell-line), using components of the canonical transforming growth factor-β signaling machinery as a model system. Furthermore, transfection reagents and control siRNA reduced the viability and proliferation of both lung fibroblasts and NIH/3T3 cells. These data collectively provide a cautionary note to investigators to carefully consider the impact of control interventions, such as mock transfections and control siRNA, in RNA interference studies with synthetic siRNA.
Jan M Kleefeldt, Agnieszka Pozarska, Claudio Nardiello, Tilman Pfeffer, István Vadász, Susanne Herold, Werner Seeger, Rory E Morty

1417 related Products with: Commercially available transfection reagents and negative control siRNA are not inert.

5.00 nmol25.00 nmol10.00 nmol5.00 nmol25.00 nmol10.00 nmol100 Tests1 mg20 3 mg10.00 nmol100 Tests

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#32745153   2020/08/03 To Up

Ectromelia-encoded virulence factor C15 specifically inhibits antigen presentation to CD4+ T cells post peptide loading.

Smallpox and monkeypox pose severe threats to human health. Other orthopoxviruses are comparably virulent in their natural hosts, including ectromelia, the cause of mousepox. Disease severity is linked to an array of immunomodulatory proteins including the B22 family, which has homologs in all pathogenic orthopoxviruses but not attenuated vaccine strains. We demonstrate that the ectromelia B22 member, C15, is necessary and sufficient for selective inhibition of CD4+ but not CD8+ T cell activation by immunogenic peptide and superantigen. Inhibition is achieved not by down-regulation of surface MHC- II or co-stimulatory protein surface expression but rather by interference with antigen presentation. The appreciable outcome is interference with CD4+ T cell synapse formation as determined by imaging studies and lipid raft disruption. Consequently, CD4+ T cell activating stimulus shifts to uninfected antigen-presenting cells that have received antigen from infected cells. This work provides insight into the immunomodulatory strategies of orthopoxviruses by elucidating a mechanism for specific targeting of CD4+ T cell activation, reflecting the importance of this cell type in control of the virus.
Katherine S Forsyth, Nathan H Roy, Elise Peauroi, Brian C DeHaven, Erik D Wold, Adam R Hersperger, Janis K Burkhardt, Laurence C Eisenlohr

2185 related Products with: Ectromelia-encoded virulence factor C15 specifically inhibits antigen presentation to CD4+ T cells post peptide loading.

1 kit(96 Wells)1 kit(96 Wells)50 1 kit(96 Wells)1 kit(96 Wells) 25UG100 µg1 kit(96 Wells)100 µg0.1 mg1 mg1 kit(96 Wells)

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#32744947   // To Up

Food Insecurity Is Associated With Higher Health Care Use And Costs Among Canadian Adults.

Food insecurity predicts poorer health, yet how it relates to health care use and costs in Canada remains understudied. Linking data from the Canadian Community Health Survey to hospital records and health care expenditure data, we examined the association of food insecurity with acute care hospitalization, same-day surgery, and acute care costs among Canadian adults, adjusting for sociodemographic characteristics. Compared with fully food-secure adults, marginally, moderately, and severely food-insecure adults presented 26 percent, 41 percent, and 69 percent higher odds of acute care admission and 15 percent, 15 percent, and 24 percent higher odds of having same-day surgery, respectively. Conditional on acute care admission, food-insecure adults stayed from 1.48 to 2.08 more days in the hospital and incurred $400-$565 more per person-year in acute care costs than their food-secure counterparts, with this excess cost representing 4.4 percent of total acute care costs. Programs reducing food insecurity, such as child benefits and public pensions, and policies enhancing access to outpatient care may lower health care use and costs.
Fei Men, Craig Gundersen, Marcelo L Urquia, Valerie Tarasuk

1814 related Products with: Food Insecurity Is Associated With Higher Health Care Use And Costs Among Canadian Adults.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100 ul10 mg100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized 5 G

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