Cytotoxic T cells (CTL) recognize short peptide epitopes presented by class I glycoproteins encoded by the major histocompatibility complex (MHC). It is not yet known whether peptides containing ...posttranslationally modified amino acids can also be recognized by CTL. To address this issue, we have studied the immunogenicity and recognition of a glycopeptide carrying an O-linked N-acetylglucosamine (GlcNAc) monosaccharide-substituted serine residue. This posttranslational modification is catalyzed by a recently described cytosolic glycosyltransferase. We show that glycosylation does not affect peptide binding to MHC class I and that glycopeptides can elicit a strong CTL response that is glycopeptide specific. Furthermore, glycopeptide recognition by cytotoxic T cells is dependent on the chemical structure of the glycan as well as its position within the peptide.
Our study has demonstrated that epithelial neutral endopeptidase (NEP) was down‐regulated transcriptionally by diesel exhaust particulate (DEP) exposure. To further understand the impact of NEP loss ...in epithelial response to DEP, we collected transcriptome profiles of the concentration‐effects of DEP in BEAS‐2B cells through a 2 × 3 factorial design NEP siRNA transfected vs. mock cells and controls vs. low, high DEP exposure. Microarray data clearly indicated that DEP exposure induced numerous gene up‐ or down‐regulation involving transcription factor activities, DNA/protein binding, and intracellular signaling cascade of chemokines, and cytokines. DEP also disturbed many gene transcriptions relating to cellular monooxygenase, GTPase, and protein kinase activities. Moreover, the integration of microarray with RNAi technique helped us to find that NEP plays an important role in the particulate relevant cellular response or the genetic susceptibility to particulate exposure. These identified genes include signal transduction of interleukin (IL)‐6, IL‐8, and chemokine(C‐X‐C motif) legend 1. NEP expression was also associated with the metabolic capability of cytochrome P450 family (CYP1A1, CYP1B1) for DEP. Collectively, the data revealed that there exists a complex molecular cascade mediated by NEP in different subcellular compartments, further influencing normal cellular functions
(Supported by HEI).
A whole-genome duplication occurred in a shared ancestor of the yeast species Saccharomyces cerevisiae, Saccharomyces castellii and Candida glabrata. Here we trace the subsequent losses of duplicated ...genes, and show that the pattern of loss differs among the three species at 20% of all loci. For example, several transcription factor genes, including STE12, TEC1, TUP1 and MCM1, are single-copy in S. cerevisiae but are retained in duplicate in S. castellii and C. glabrata. At many loci, different species have lost different members of a duplicated gene pair, so that 4-7% of single-copy genes compared between any two species are not orthologues. This pattern of gene loss provides strong evidence for speciation through a version of the Bateson-Dobzhansky-Muller mechanism, in which the loss of alternative copies of duplicated genes leads to reproductive isolation. We show that the lineages leading to the three species diverged shortly after the whole-genome duplication, during a period of precipitous gene loss. The set of loci at which single-copy paralogues are retained is biased towards genes involved in ribosome biogenesis and genes that evolve slowly, consistent with the hypothesis that reciprocal gene loss is more likely to occur between duplicated genes that are functionally indistinguishable. We propose a simple, unified model in which a single mechanism-passive gene loss-enabled whole-genome duplication and led to the rapid emergence of new yeast species.
Focusing on the work values of Chinese hospitality and tourism management (HTM) undergraduate students, this article aims to identify any segment existing among HTM students in China based on work ...values, as well as to investigate any relationship between work values and career choice intention across the derived student segments. Work values were measured by a self-administered questionnaire based on Super's (
1970
) Work Value Inventory; career choice intention was assessed by a single-item instrument. The data were collected from 566 HTM undergraduate students in five major cities in China. Cluster analysis was employed to identify homogeneous groups of responses to the specified work-value criteria. Multiple regression analyses were then conducted to investigate whether and to what extent the work-value dimensions exerted a significant influence over hospitality and tourism career choice intention across different segments. As a result, two segments, "medium achievers" and "high achievers," were identified. The structures for predicting work-value dimensions on career choice within individual segment models appear to be different compared to the structure for the overall student group model. Conclusions were also reached on the hierarchy of work values and the demographic differences in work values in this study. Recommendations are made based on the findings.
本文研究的重心是中国酒店及旅游业管理(HTM)大学本科生的工作价值观，目的是确定中国HTM学生在工作价值观上是否存在区隔，及研究各学生区隔的工作价值观及职业选择意向之间是否存在关系。本文以一份根据 Super (
1970
) 的工作价值观总表 (Work Value Inventory) 而设计的自填式问卷衡量工作价值观，职业选择意向则利用单项工具评估。本文从5个中国主要城市收集了566名HTM学生的数据，利用聚类分析(cluster analysis)，根据指定的工作价值标准将受访学生的回应归类为同性质的组群。接着采用多重回归分析找出各工作价值观的因素会否影响不同区隔的HTM学生的职业选择意向，或影响有多深远。最后得出"中等成功"和"非常成功"两组学生区隔。就预测各工作价值观的因素对职业选择的影响而言，个别区隔模型的结构与整体学生区隔模型的结构并不相同。最后，本文得出工作价值观层级及人口变项对工作价值观构成影响的结论，并根据研究结果进一步提出建议。
Neutral endopeptidase (NEP) is a 90‐110 kDa zinc‐dependent, type II integral membrane protein abundantly expressed on airway epithelial cells. To determine the molecular effects of diesel exhaust ...particulates (DEP) on NEP expression, we analyzed temporal/concentrational patterns following exposure to 5‐60 μg/ml standard DEP, SRM 2975 by using BEAS‐2B cells. Data show that the NEP mRNA levels decreased in a time‐dependent manner during 24 h DEP incubation. The significant change was detected as early as 8 h after DEP addition, persisting up to 24 h. To examine the sensitivity and specificity of NEP mRNA responses, we conducted a dose‐effect experiment at concentrations of 0 (air controls), 5, 10, 20, 40, 60 μg/ml DEP. After 24 h exposure, NEP mRNA exhibits a concentration‐dependent downregulation, with a maximum effect beginning at the exposure concentration of 40 μg/ml. Moreover, NEP protein and activity also decreased in a concentration‐dependent manner after 24‐h incubation. Todetermine whether the repression of NEP by DEP, occurs at the transcriptional or post‐transcriptionallevel, we assessed the effect of DEP on NEP mRNA transcriptstability. BEAS‐2B cells were treated with actinomycin D, exposed to DEP (40 μg/ml) or vehicle, and then assayed for NEPmRNA levels at various time points up to 24 h. Real‐time PCRindicated no difference in the rate of NEP mRNA degradationbetween DEP and vehicle‐treated samples, thusdemonstrating that DEP regulation of NEP gene expressionlikely occurs at the transcriptional level
(Supported by HEI).
The project presented in this paper aims to formulate a recommendation framework that consolidates the higher education students' particulars such as their academic background, current study and ...student activity records, their attended higher education institution's expectations of graduate attributes and self-assessment of their own generic competencies. The gap between the higher education students' generic competence development and their current statuses such as their academic performance and their student activity involvement was incorporated into the framework to come up with a recommendation for the student activities that lead to their generic competence development. For the formulation of the recommendation framework, the data mining tool Orange with some programming in Python and machine learning models was applied on 14,556 students' activity and academic records in the case higher education institution to find out three major types of patterns between the students' participation of the student activities and (1) their academic performance change, (2) their programmes of studies, and (3) their English results in the public examination. These findings are also discussed in this paper.
ABSTRACT
Candida parapsilosis
is responsible for ca. 15% of
Candida
infections and is of particular concern in neonates and surgical intensive care patients. The related species
Candida albicans
has ...recently been shown to possess a functional mating pathway. To analyze the analogous pathway in
C. parapsilosis
, we carried out a genome sequence survey of the type strain. We identified ca. 3,900 genes, with an average amino acid identity of 59% with
C. albicans
. Of these, 23 are predicted to be predominantly involved in mating. We identified a genomic locus homologous to the
MTL
a
mating type locus of
C. albicans
, but the
C. parapsilosis
type strain has at least two internal stop codons in the
MTL
a
1
open reading frame, and two predicted introns are not spliced. These stop codons were present in
MTL
a
1
of all eight
C. parapsilosis
isolates tested. Furthermore, we found that all isolates of
C. parapsilosis
tested appear to contain only the
MTL
a
idiomorph at the presumptive mating locus, unlike
C. albicans
and
C. dubliniensis
.
MTLα
sequences are present but at a different chromosomal location. It is therefore likely that all (or at least the majority) of
C. parapsilosis
isolates have a mating pathway that is either defective or substantially different from that of
C. albicans
.
Phagocytosis of microbial pathogens is essential for the host immune response to infection. Our previous work has shown that lipooligosaccharide (LOS) expression on the surface of Neisseria ...meningitidis (Nm) is essential for phagocytosis, but the receptor involved remained unclear. In this study, we show that human CR3 (CD11b-CD18) and CR4 (CD11c-CD18) are phagocytic receptors for Nm as illustrated by the capacity of CR3- and CR4-transfected Chinese hamster ovary (CHO) cells to facilitate Nm uptake. A CR3-signalling mutant failed to internalize Nm, showing that the ability of CR3 to signal is essential for phagocytosis. Internalization of Nm by CR3-transfected CHO cells could be inhibited by the presence of CR3-specific antibodies. Furthermore, dendritic cells from leukocyte adhesion deficiency-1 patients, who have diminished expression of b2 integrins, showed markedly reduced phagocytosis of Nm. The CR3-mediated phagocytosis required the presence of lipopolysaccharide-binding protein (LBP). Furthermore, the expression of LOS by Nm was essential for LBP binding and phagocytosis via CR3. These results reveal a critical role of CR3 and LBP in the phagocytosis of Nm and provide important insights into the initial interaction meningococci have with the immune system.
We developed a wafer-scale, monolithic, 3-D integrated circuit process that features three active layers: a silicon base layer with CMOS circuitry, a second layer of germanium (Ge) PMOS devices, and ...a top layer of AlOxNy resistive random access memory (RRAM) cells. The temperatures of all processes, following the fabrication of the CMOS circuitry, are below 400°C to ensure no damage to the CMOS circuitry. The Ge layer is applied as an array of islands using low-temperature aligned bonding, followed by cleaving at the buried layer of implanted hydrogen ions. The Ge PMOS devices are lithographically aligned to the underlying CMOS and feature metal gates over high-κ dielectric. The RRAM devices built into the third layer exhibit sub-μA switched currents. This process is attractive for a compact field-programmable gate array with reduced area, delay, and power.
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