267 research outputs found
Glycoprotein biosynthesis in Saccharomyces cerevisiae: ngd29, an N-glycosylation mutant allelic to och1 having a defect in the initiation of outer chain formation
AbstractOuter chain glycosylation in Saccharomyces cerevisiae leads to heterogeneous and immunogenic asparagine-linked saccharide chains containing more than 50 mannose residues on secreted glycoproteins. Using a [3H]mannose suicide selection procedure a collection of N-glycosylation defective mutants (designated ngd) was isolated. One mutant, ngd29, was found to have a defect in the initiation of the outer chain and displayed a temperature growth sensitivity at 37°C allowing the isolation of the corresponding gene by complementation. Cloning, sequencing and disruption of NGD29 showed that it is a non lethal gene and identical to OCH1. It complemented both the glycosylation and growth defect. Membranes isolated from an ngd29 disruptant or an ngd29mnn1 double mutant were no longer able, in contrast to membranes from wild type cells, to transfer mannose from GDPmannose to Man8GlcNAc2, the in vivo acceptor for building up the outer chain. Heterologous expression of glucose oxidase from Aspergillus niger in an ngd29mnn1 double mutant produced a secreted uniform glycoprotein with exclusively Man8GlcNAc2 structure that in wild type yeast is heavily hyperglycosylated. The data indicate that this mutant strain is a suitable host for the expression of recombinant glycoproteins from different origin in S. cerevisiae to obtain mammalian oligomannosidic type N-linked carbohydrate chains
Modulation of the maternal immune system by the pre-implantation embryo
Background: A large proportion of pregnancy losses occur during the pre-implantation period, when the developing embryo is elongating rapidly and signalling its presence to the maternal system. The molecular mechanisms that prevent luteolysis and support embryo survival within the maternal environment are not well understood. To gain a more complete picture of these molecular events, genome-wide transcriptional profiles of reproductive day 17 endometrial tissue were determined in pregnant and cyclic Holstein-Friesian dairy cattle
Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID. The proband is heterozygous for the TNFRSF13B/TACI C104R mutation and meets the Ameratunga et al. diagnostic criteria for CVID and the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Her son has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency, but has not inherited the TNFRSF13B/TACI mutation. Her brother, homozygous for the TNFRSF13B/TACI mutation, is in good health despite profound hypogammaglobulinemia and mild cytopenias. We hypothesised that a second unidentified mutation contributed to the symptomatic phenotype of the proband and her son. Whole-exome sequencing of the family revealed a de novo nonsense mutation (T168fsX191) in the Transcription Factor 3 (TCF3) gene encoding the E2A transcription factors, present only in the proband and her son. We demonstrate mutations of TNFRSF13B/TACI impair immunoglobulin isotype switching and antibody production predominantly via T-cell-independent signalling, while mutations of TCF3 impair both T-cell-dependent and -independent pathways of B-cell activation and differentiation. We conclude that epistatic interactions between mutations of the TNFRSF13B/TACI and TCF3 signalling networks lead to the severe CVID-like disorder and SLE in the proband.We thank AMRF, A+ Trust, IDFNZ,
ASCIA and the Australian National Health and Medical Research Council
(NHMRC, Program Grant 1054925, Project Grant 1127198 and Independent
Research Institutes Infrastructure Support Scheme Grant 361646) for grant
support. We also received support from Bloody Long Way (BLW) the Victorian
State Government Operational Infrastructure scheme and Walter and Eliza Hall
Institute (WEHI) Innovation Grant. CAS is supported by NHMRC
postgraduate scholarship 1075666
Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non‐consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium‐modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID. The proband is heterozygous for the TNFRSF13B/TACI C104R mutation and meets the Ameratunga et al. diagnostic criteria for CVID and the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Her son has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency, but has not inherited the TNFRSF13B/TACI mutation. Her brother, homozygous for the TNFRSF13B/TACI mutation, is in good health despite profound hypogammaglobulinemia and mild cytopenias. We hypothesised that a second unidentified mutation contributed to the symptomatic phenotype of the proband and her son. Whole‐exome sequencing of the family revealed a de novo nonsense mutation (T168fsX191) in the Transcription Factor 3 (TCF3) gene encoding the E2A transcription factors, present only in the proband and her son. We demonstrate mutations of TNFRSF13B/TACI impair immunoglobulin isotype switching and antibody production predominantly via T‐cell‐independent signalling, while mutations of TCF3 impair both T‐cell‐dependent and ‐independent pathways of B‐cell activation and differentiation. We conclude that epistatic interactions between mutations of the TNFRSF13B/TACI and TCF3 signalling networks lead to the severe CVID‐like disorder and SLE in the proband.We thank AMRF, A+ Trust, IDFNZ,ASCIA and the Australian National Health and Medical Research Council(NHMRC, Program Grant 1054925, Project Grant 1127198 and IndependentResearch Institutes Infrastructure Support Scheme Grant 361646) for grantsupport. We also received support from Bloody Long Way (BLW) the VictorianState Government Operational Infrastructure scheme and Walter and Eliza HallInstitute (WEHI) Innovation Grant. CAS is supported by NHMRCpostgraduate scholarship 107566
Seasonal Variations in Vegetation Indices derived from in situ Type Vegetation Monitoring System at typical landcovers in Japan : From the Observation Results in PGLIERC and Lake Biwa Project
研究概要:本研究では光学センサー搭載衛星データの検証及び地表面フラックスとの対応関係を調べるために簡易式の地上設置型植生モニタリングシステムを日本を代表する土地被覆上(草地,水田,アカマツ林,落葉広葉樹)に設置し,それぞれの土地被覆から得られる植生指標の季節変化について示した.その結果,以下の知見が得られた;1.草原系(草地・水田)では各植生の季節変化特性を良好にモニターすることが可能である,2.森林系(アカマツ林・落葉広葉樹)ではセンサーとキャノピーの距離が近すぎるため,思うような結果を得ることが出来なかった.3.ただし全般としては各土地被覆特性を示す連続したデータを取得することができ,システムの妥当性を示すことができた
Self-Assembled Nanometer-Scale Magnetic Networks on Surfaces: Fundamental Interactions and Functional Properties
Nanomagnets of controlled size, organized into regular patterns open new perspectives in the fields of nanoelectronics, spintronics, and quantum computation. Self-assembling processes on various types of substrates allow designing fine-structured architectures and tuning of their magnetic properties. Here, starting from a description of fundamental magnetic interactions at the nanoscale, we review recent experimental approaches to fabricate zero-, one-, and two-dimensional magnetic particle arrays with dimensions reduced to the atomic limit and unprecedented areal density. We describe systems composed of individual magnetic atoms, metal-organic networks, metal wires, and bimetallic particles, as well as strategies to control their magnetic moment, anisotropy, and temperature-dependent magnetic behavior. The investigation of self-assembled subnanometer magnetic particles leads to significant progress in the design of fundamental and functional aspects, mutual interactions among the magnetic units, and their coupling with the environment
Case Report Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1
- …