Structure of the substrate-engaged SecA-SecY protein translocation machine.

The Sec61/SecY channel allows the translocation of many proteins across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane. In bacteria, most secretory proteins are transported post-translationally through the SecY channel by the SecA ATPase. How a polypeptide is moved through the SecA-SecY complex is poorly understood, as structural information is lacking. Here, we report an electron cryo-microscopy (cryo-EM) structure of a translocating SecA-SecY complex in a lipid environment. The translocating polypeptide chain can be traced through both SecA and SecY. In the captured transition state of ATP hydrolysis, SecAs two-helix finger is close to the polypeptide, while SecAs clamp interacts with the polypeptide in a sequence-independent manner by inducing a short β-strand. Taking into account previous biochemical and biophysical data, our structure is consistent with a model in which the two-helix finger and clamp cooperate during the ATPase cycle to move a polypeptide through the channel

Hybrid Nanosecond Laser Processing and Heat Treatment for Rapid Preparation of Super-Hydrophobic Copper Surface

The super-hydrophobic copper surface was obtained by using a nanosecond pulsed laser. Different micro- and nano-structures were fabricated by changing the laser scanning interval and scanning speed, before heating in an electric heater at 150 °C for two hours to explore the effect of laser parameters and heat treatment on the wettability of the copper surface. It was found that the laser-treated copper surface is super-hydrophilic, and then, after the heat treatment, the surface switches to hydrophobic or even super-hydrophobic. The best super-hydrophobic surface’s apparent contact angle (APCA) was 155.6°, and the water sliding angle (WSA) was 4°. Super-hydrophobic copper is corrosion-resistant, self-cleaning, and dust-proof, and can be widely used in various mechanical devices

Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection

The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4+, CD8+ T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effects of Anaerobic Fermentation on Black Garlic Extract by Lactobacillus: Changes in Flavor and Functional Components

The purpose of this study is to investigate the potential application of probiotics in the development of novel functional foods based on black garlic. The single-factor analysis (extraction temperatures, solid-to-liquid ratios, and extraction times) and the response surface methodology were firstly used to optimize hot water extraction of soluble solids from black garlic. The optimal extraction conditions were temperature 99.96°C, solid-to-liquid ratio 1:4.38 g/ml, and extracting 2.72 h. The effects of Lactobacillus (Lactobacillus plantarum, Lactobacillus rhamnosus, and co-culture of them) fermentation on the physicochemical properties of black garlic extract broth were studied for the first time. Artificial and electronic sensory evaluations demonstrated that fermentation significantly influenced the sensory characteristics. The variations of metabolites in different broth samples (S1, unfermented; S2, 1-day fermentation by L. plantarum; S3, 2-day fermentation by L. rhamnosus; and S4, 1-day fermentation by co-cultured Lactobacillus) were further investigated by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry/mass spectrometry analysis. As a result, Lactobacillus fermentation significantly reduced the pH; increased the contents of the total acid, amino nitrogen, total polyphenol, and total flavonoid; and reduced the content of 5-hydroxymethylfurfural (a carcinogenic component) by 25.10–40.81% in the black garlic extract. The contents of several components with unpleasant baking flavors (e.g., furfural, 2-acetylfuran, and 5-methyl furfural) were reduced, whereas the contents of components with green grass, floral, and fruit aromas were increased. More importantly, the contents of several functional components including lactic acid, Gly-Pro-Glu, sorbose, and α-CEHC (3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-propanoic acid) were increased after Lactobacillus fermentation. The results demonstrated the potential of probiotic fermentation to improve the quality of black garlic. This work will provide an insight into the strategic design of novel black garlic products and facilitate the application of black garlic in functional foods

Effects of Si/Al Ratios on the Bulk-Type Zeolite Formation Using Synthetic Metakaolin-Based Geopolymer with Designated Composition

In this paper, synthetic metakaolin with fixed composition (Al2O3·2SiO2) was produced by a simple chemosynthetic route. The chemosynthetic metakaolin can eliminate the influence of impurities in metakaolin from natural kaolin minerals. The synthetic metakaolin together with NaOH and SiO2-sol were used to prepare Na-based geopolymer precursors with various molar ratios of Si/Al. The molar ratios of Si/Al from 1 to 2 were tailored by adding different contents of SiO2-sol. Zeolite/geopolymer composites or monolith-type zeolite were successfully fabricated from synthetic metakaolin-based geopolymer through a hydrothermal process. The effects of Si/Al ratios on the phase composition and microstructure of the produced zeolite/geopolymer composites or zeolites were studied. The results proved that the composition of synthetic metakaolin and geopolymer precursors can be facilely tuned, and the monolithic geopolymer precursors can be mostly, or even totally, transformed into zeolite after hydrothermal treatment