Infections caused by enterohemorrhagic Escherichia coli (EHEC) can lead to diarrhea with abdominal cramps and sometimes are complicated by severe hemolytic uremic syndrome. EHEC secretes effector ...proteins into host cells through a type III secretion system that is composed of proteins encoded by a chromosomal island, locus for the enterocyte effacement (LEE). EspA is the major component of the filamentous structure connecting the bacteria and the host's cells. Synthesis and secretion of EspA must be carefully controlled since the protein is prone to polymerize. CesAB, CesA2, and EscL have been identified as being able to interact with EspA. Furthermore, the intracellular level of EspA declines when cesAB, cesA2, and escL are individually deleted. Here, we report a LEE gene named l0033, which also affects the intracellular level of EspA. We renamed l0033 as escA since its counterpart in enteropathogenic E. coli has been recently described. Similar to CesAB, EscL, and CesA2, EscA interacts with EspA and enhances the protein stability of EspA. However, EscA is also able to interact with inner membrane-associated EscL, CesA2, and EscN, but not with cytoplasmic CesAB. In terms of gene organizations, escA locates in LEE3. Expression of EscA is faithfully regulated via Mpc, the first gene product of LEE3. Since Mpc is tightly regulated to low level, we suggest that EscA is highly synchronized and critical to the process of escorting EspA to its final destination.
Unlike the well-defined long-range order that characterizes crystalline metals, the atomic arrangements in amorphous alloys remain mysterious at present. Despite intense research activity on metallic ...glasses and relentless pursuit of their structural description, the details of how the atoms are packed in amorphous metals are generally far less understood than for the case of network-forming glasses. Here we use a combination of state-of-the-art experimental and computational techniques to resolve the atomic-level structure of amorphous alloys. By analysing a range of model binary systems that involve different chemistry and atomic size ratios, we elucidate the different types of short-range order as well as the nature of the medium-range order. Our findings provide a reality check for the atomic structural models proposed over the years, and have implications for understanding the nature, forming ability and properties of metallic glasses.
Lesion mimic mutants spontaneously produce disease spots in the absence of biotic or abiotic stresses. Analyzing lesion mimic mutants’ sheds light on the mechanisms underlying programmed cell death ...and defense-related responses in plants. Here, we isolated and characterized the rice (
Oryza sativa
)
spotted leaf 36
(
spl36
) mutant, which was identified from an ethyl methanesulfonate-mutagenized
japonica
cultivar Yundao population.
spl36
displayed spontaneous cell death and enhanced resistance to rice bacterial pathogens. Gene expression analysis suggested that
spl36
functions in the disease response by upregulating the expression of defense-related genes. Physiological and biochemical experiments indicated that more cell death occurred in
spl36
than the wild type and that plant growth and development were affected in this mutant. We isolated
SPL36
by map-based cloning. A single base substitution was detected in
spl36
, which results in a cysteine-to-arginine substitution in
SPL36
.
SPL36
is predicted to encode a receptor-like protein kinase containing leucine-rich domains that may be involved in stress responses in rice.
spl36
was more sensitive to salt stress than the wild type, suggesting that
SPL36
also negatively regulates the salt-stress response. These findings suggest that
SPL36
regulates the disease resistance response in rice by affecting the expression of defense- and stress-related genes.
Bulk metallic glasses (MGs) with tunable plasticity and strength have been reported recently. Using Cu–Zr and Cu–Zr–Al MG models, here we illustrate how and why alloy composition and cooling history ...influence the initial flow behavior in the early stage of plasticity. Starting from Cu
46Zr
54, either increasing the Cu concentration, or substituting Al for a few percent of Zr, increases the resistance to the initiation of plastic flow, the softening after the local yielding, and the propensity for strain localization. These effects are shown to be intrinsic to the uniform, fully amorphous MGs and rooted in their internal structure. Our quantitative monitoring of the local environment, especially the role of full-icosahedral clusters in shear transformations, identifies the fertile and resistant structural entities controlling deformation. The structural mechanisms have implications for macroscopic plasticity, and the alloy dependence of the MG structure reveals a microscopic origin underlying the varying mechanical properties.
Anti-interferon- γ (IFN-γ) autoantibodies (anti-IFN-γ Abs) have been increasingly recognized as an important cause of disseminated nontuberculous mycobacterial (DNTM) infection, and identification of ...this immunodeficiency impacts clinical management. However, the protean disease manifestations and inaccessibility to diagnostic tests in clinical settings hamper its early diagnosis. Here, we sought to determine whether QuantiFERON-TB Gold In-tube (QFT-GIT), a commercialized IFN-γ release assay, could be used to screen for neutralizing anti-IFN-γ Abs among previously healthy adults with DNTM infection.
Non-HIV patients with DNTM infection were prospectively enrolled for the QFT-GIT assays. We measured their plasma concentration of anti-IFN-γ Abs and their neutralizing capacity through enzyme-linked immunosorbent assay and flow cytometry. We then analysed the correlation between QFT-GIT results and the presence of neutralizing anti-IFN-γ Abs among patients with and without previously recognized immunosuppression, respectively.
Irrespective of the autoantibody concentration or disease activity, all patients with neutralizing anti-IFN-γ Abs (100%, 30/30) had indeterminate QFT-GIT results because of extremely low or undetectable IFN-γ levels in the mitogen tubes. None of the four DNTM patients who were previously healthy and tested negative of anti-IFN-γ Abs had an indeterminate QFT-GIT result, and their IFN-γ levels in the mitogen tube were significantly higher than those of the patients with anti-IFN-γ Abs (8.28 IU/mL vs. 0.05 IU/mL, p 0.001).
An indeterminate QFT-GIT result because of undetectable or extremely low IFN-γ level in the mitogen tube suggests the presence of neutralizing anti-IFN-γ Abs in a previously healthy patient with DNTM infection.
HER2 has a predictive value in gastric cancer. However, its association with prognosis remains uncertain. The aim of our study was to estimate the HER2-positive rate in Chinese gastric cancers, ...compare the classical fluorescence in situ hybridization (FISH) method with the novel bright-field dual color silver-enhanced in situ hybridization (DSISH) detection system, and evaluate the relationship between the HER2 status and prognosis.
Seven hundred and twenty-six resected gastric cancers separately from four clinical centers in China were examined for HER2 by immunohistochemistry (IHC), FISH, and DSISH.
The HER2-positive rate was 13%. The consistency between FISH and DSISH results was high (99%; κ = 0.958; P < 0.001). Tumor heterogeneity and polysomy were the main reasons for inconsistency. There was no significant difference in the 3-year overall survival (OS) between HER2-positive and -negative patients (P = 0.959). Multivariate analysis showed that HER2 was not an independent prognostic factor.
HER2 overexpression and amplification occur in a significant number of Chinese gastric cancer patients. Given the obvious advantages and high consistency with FISH, DSISH was superior for evaluating HER2 amplification in gastric cancer. HER2 was not a prognostic factor for gastric cancer in our study.
Atomic packing in metallic glasses is not completely random but displays various degrees of structural ordering. While it is believed that local structures profoundly affect the properties of ...glasses, a fundamental understanding of the structure–property relationship has been lacking. In this article, we provide a microscopic picture to uncover the intricate interplay between structural defects and dynamic properties of metallic glasses, from the perspective of computational modeling. Computational methodologies for such realistic modeling are introduced. Exploiting the concept of quasi-equivalent cluster packing, we quantify the structural ordering of a prototype metallic glass during its formation process, with a new focus on geometric measures of subatomic “voids.” Atomic sites connected with the voids are found to be crucial in terms of understanding the dynamic, including vibrational and atomic transport, properties. Normal mode analysis is performed to reveal the structural origin of the anomalous boson peak (BP) in the vibration spectrum of the glass, and its correlation with atomic packing cavities. Through transition-state search on the energy landscape of the system, such structural disorder is found to be a facilitating factor for atomic diffusion, with diffusion energy barriers and diffusion pathways significantly varying with the degree of structural relaxation/ordering. The implications of structural defects for the mechanical properties of metallic glasses are also discussed.
An ultra‐wideband metamaterial absorber (MA) is proposed for 5G communication, which features a resistive frequency selective surface printed on a PET (polyethylene terephthalate) layer and a ground ...layer of resistive film. The proposed MA can provide over 90% absorptivity in the frequency range of 11.2–42.8 GHz. Moreover, it is insensitive to polarization and wide incident angles. The effective medium theory and multi‐reflection interference theory are used to interpret the broadband absorption mechanism. The surface current distribution at three absorption peaks is investigated to further study the physical mechanism behind the wideband absorption. The measured results of the fabricated prototype are in good agreement with the simulation ones, thus verifying the robustness of the design. The presented MA can probably be used in electromagnetic shielding of 5G signals.
Previous mass screening studies have shown that IgA antibodies against Epstein–Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody ...screening for NPC-specific mortality remains unknown.
A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City.
Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37–1.79, lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09–0.49).
IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis.
NCT00941538.
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