Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

Porcine epidemic diarrhea virus (PEDV) causes acute watery diarrhea and high mortality in newborn piglets. Activation of intestinal mucosal immunity is crucial to anti-PEDV infection. To develop a vaccine capable of stimulating intestinal mucosal immunity, we prepared a bacterium (Lactococcus lactis)-like particle (BLP) vaccine (S1-BLPs) displaying the S1 protein, a domain of PEDV spike protein (S), based on gram-positive enhancer matrix (GEM) particle display technology. We further compared the effects of different vaccination routes on mucosal immune responses in mice induced by S1-BLPs. The specific IgG titer in serum of intramuscularly immunized mice with S1-BLPs was significantly higher than that of the intranasally administered. The specific IgA antibody was found in the serum and intestinal lavage fluid of mice vaccinated intranasally, but not intramuscularly. Moreover, the intranasally inoculated S1-BLPs induced higher levels of IFN-γ and IL-4 in serum than the intramuscularly inoculated. In addition, the ratio of serum IgG2a/IgG1 of mice inoculated intramuscularly was significantly higher with S1-BLPs compared to that of with S1 protein, suggesting that the immune responses induced by S1-BLPs was characterized by helper T (Th) cell type 1 immunity. The results indicated that S1-BLPs induced systemic and local immunity, and the immunization routes significantly affected the specific antibody classes and Th immune response types. The intranasally administered S1-BLPs could effectively stimulate intestinal mucosal specific secretory IgA response. S1-BLPs have the potential to be developed as PEDV mucosal vaccine

Two-element interferometer for millimeter-wave solar flare observations

In this paper, we present the design and implementation of a two-element interferometer working in the millimeter wave band (39.5 GHz - 40 GHz) for observing solar radio emissions through nulling interference. The system is composed of two 50 cm aperture Cassegrain antennas mounted on a common equatorial mount, with a separation of 230 wavelengths. The cross-correlation of the received signals effectively cancels the quiet solar component of the large flux density (~3000 sfu) that reduces the detection limit due to atmospheric fluctuations. The system performance is obtained as follows: the noise factor of the AFE in the observation band is less than 2.1 dB, system sensitivity is approximately 12.4 K (~34 sfu) with an integration time constant of 0.1 ms (default), the frequency resolution is 153 kHz, and the dynamic range is larger than 30 dB. Through actual testing, the nulling interferometer observes a quiet sun with a low level of output fluctuations (of up to 50 sfu) and has a significantly lower radiation flux variability (of up to 190 sfu) than an equivalent single-antenna system, even under thick cloud cover. As a result, this new design can effectively improve observation sensitivity by reducing the impact of atmospheric and system fluctuations during observation

Association between Dietary Patterns and Precocious Puberty in Children: A Population-Based Study

Objective. The aim of the present study was to investigate the association between dietary patterns and precocious puberty among Shanghai children. Methods. A cross-sectional study was conducted among Shanghai children by multistage stratified cluster random sampling in June 2014. Diet was assessed using a simplified food frequency questionnaire (FFQ). Height, weight, and Tanner stages of breast development, pubic hair growth, and testicular volume were carefully measured. Exploratory factor analysis was used to identify dietary patterns, and logistic regression analysis was used to assess the association between dietary patterns and precocious puberty. Results. Three distinct dietary patterns, “traditional diet,” “unhealthy diet,” and “protein diet,” were established. Neither the “traditional diet” pattern nor the “protein diet” pattern showed any association with precocious puberty, taking gender, BMI, and adjustment factors into consideration. The “unhealthy diet” pattern was significantly positively associated with precocious puberty in both boys (OR = 1.24, 95% CI = 1.02–1.51) and girls (OR = 1.31, 95% CI = 1.10–1.56). The relationship remained positive only for girls (OR = 1.25, 95% CI = 1.04–1.49) after adjustment for age and BMI but statistically nonsignificant after further adjustment for socioeconomic factors in both boys and girls. Conclusions. Dietary patterns were found to be related to precocious puberty among Shanghai children

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Similarity-Based 3D Atmospheric Nucleation Data Visualization and Analysis

Atmospheric nucleation is a process of phase transformation, which serves a significant role in many atmospheric and technological processes. To simulate atmospheric nucleation activities, certain molecular models with three-dimensional (3-D) structures are generated. Analyzing these 3-D molecular models can help promote understanding of nucleation processes. Unfortunately, the ability to understand atmospheric nucleation processes is greatly restricted due to lack of efficient visual data exploration tools. In this paper, we present a data visualization solution to visualize and classify 3-D molecular crystals. We developed a novel algorithm for calculating similarity between the 3-D molecular crystals, and further improved the overall system performance with GPU (graphics processing unit) acceleration

Similarity-Based 3D Atmospheric Nucleation Data Visualization and Analysis

Atmospheric nucleation is a process of phase transformation, which serves a significant role in many atmospheric and technological processes. To simulate atmospheric nucleation activities, certain molecular models with three-dimensional (3-D) structures are generated. Analyzing these 3-D molecular models can help promote understanding of nucleation processes. Unfortunately, the ability to understand atmospheric nucleation processes is greatly restricted due to lack of efficient visual data exploration tools. In this paper, we present a data visualization solution to visualize and classify 3-D molecular crystals. We developed a novel algorithm for calculating similarity between the 3-D molecular crystals, and further improved the overall system performance with GPU (graphics processing unit) acceleration

Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity-related diseases

Obesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti-inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure-activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in-depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed