Insufficient water for irrigation is a common problem in the Canterbury Region of New Zealand. Farmers have the option of applying for resource consent or joining a community irrigation scheme to take water. Water supply becomes more problematic during drought seasons as farmers must adhere to water restrictions imposed by the water authority.
View Article and Find Full Text PDFThe nucleoskeleton and cytoskeleton are important protein networks that govern cellular behavior and are connected together by the linker of nucleoskeleton and cytoskeleton (LINC) complex. Mutations in LINC complex components may be relevant to cancer, but how cell-level changes might translate into tissue-level malignancy is unclear. We used glandular epithelial cells in a three-dimensional culture model to investigate the effect of perturbations of the LINC complex on higher order cellular architecture.
View Article and Find Full Text PDFIntroduction: Interferon alpha 2B (IFN-α) therapy in malignant melanoma has improved relapse free survival and overall survival but is considerably toxic and lowers the overall quality of life (QoL) substantially. A significant number of patients do not complete the full duration (one year) of therapy.
Objective: The aim of this study was to evaluate patients' ability to tolerate IFN-α therapy and to compare our results to reported data in the literature.
The nuclear envelope (NE) is critical for numerous fundamental cellular functions, and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin A, Sun2 and a minimal INM-targeting motif. These studies identify vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM.
View Article and Find Full Text PDFMechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity.
View Article and Find Full Text PDFBackground: Cancer-associated isocitrate dehydrogenase (IDH) mutations block normal cellular differentiation via production of the oncometabolite, R-2-hydroxyglutarate. In patients with acute myeloid leukemia (AML) receiving targeted mutant IDH inhibitor therapy, neutrophil recovery within the setting of clinical differentiation syndrome (DS) has been anecdotally described.
Patients And Methods: We describe 3 patients who developed clinically apparent DS during monotherapy with the mutant IDH1 inhibitor, AG-120, for relapsed/refractory AML.
The BioID method uses a promiscuous biotin ligase to detect protein-protein associations as well as proximate proteins in living cells. Here we report improvements to the BioID method centered on BioID2, a substantially smaller promiscuous biotin ligase. BioID2 enables more-selective targeting of fusion proteins, requires less biotin supplementation, and exhibits enhanced labeling of proximate proteins.
View Article and Find Full Text PDFIntroduction: Molecular profiling (MP) has been used as a technique to identify treatment regimens for individual patient's cancer. The results of MP has been used to guide targeted therapy specific to each patient's tumor that resulted in a longer progression free survival (PFS) compared to the last conventional treatment. This study aims to provide further data to delineate the PFS of patients who get treated with targeted therapy based on MP.
View Article and Find Full Text PDFBackground: Diffuse large B-cell lymphoma accounts for the large majority of AIDS-related non-Hodgkin lymphoma. Traditionally, this lymphoma has been treated with CHOP-like regimens with the recent addition of rituximab. We report a unique case where an HIV-infected patient with diffuse large B-cell lymphoma had complete regression of the lymphoma with continued antiretroviral therapy (ART) after chemotherapy was stopped.
View Article and Find Full Text PDFThe fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3' linkage; CGL2 for motifs with fucose in a 2' linkage; and RSL for fucose in all linkages.
View Article and Find Full Text PDFCell nuclei are physically integrated with the cytoskeleton through the linker of nucleoskeleton and cytoskeleton (LINC) complex, a structure that spans the nuclear envelope to link the nucleoskeleton and cytoskeleton. Outer nuclear membrane KASH domain proteins and inner nuclear membrane SUN domain proteins interact to form the core of the LINC complex. In this review, we provide a comprehensive analysis of the reported protein-protein interactions for KASH and SUN domain proteins.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2014
Proximity-dependent biotin identification (BioID) is a method for identifying protein associations that occur in vivo. By fusing a promiscuous biotin ligase to a protein of interest expressed in living cells, BioID permits the labeling of proximate proteins during a defined labeling period. In this study we used BioID to study the human nuclear pore complex (NPC), one of the largest macromolecular assemblies in eukaryotes.
View Article and Find Full Text PDFClarkson's syndrome, also called idiopathic systemic capillary leak syndrome is a rare condition characterised by vascular hyper permeability resulting in extreme intravascular volume depletion. The syndrome is unique and almost paradoxical in its presentation, with findings initially suggesting overwhelming heart failure, but in reality the extra vascular fluid represents overt capillary leak, with ultimate intravascular volume depletion, a low output state and hypovolemic shock. Previously described characteristics have classically included severe oedema and anasarca with rapid, profound shock, typically accompanied by haemoconcentration.
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