Identification of diagnostic signatures associated with immune infiltration in Alzheimer’s disease by integrating bioinformatic analysis and machine-learning strategies

ObjectiveAs a chronic neurodegenerative disorder, Alzheimer’s disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology.MethodsThe expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD.ResultsA total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells.ConclusionMAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression

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

Increases in Genistein in <i>Medicago sativa</i> Confer Resistance against the <i>Pisum</i> Host Race of <i>Acyrthosiphon pisum</i>

Interspecific interaction with host plants have important consequences for the host race formation of herbivorous insects. Plant secondary metabolites, particularly those that are involved in host races specializing on plants, warrant the theory of host specialization. Acyrthosiphon pisum comprises various host races that adapt to different Fabaceae plants, which provides an ideal system for determining the behavioral and physiological mechanisms underlying host-adaptive diversification. The current study evaluated the effects of host transfer on population fitness, feeding behavior and the transcriptome-wide gene expression of the two host races of A. pisum, one of which was originally from Medicago sativa and the other from Pisum sativum. The results showed that the Pisum host race of A. pisum had a lower population abundance and feeding efficiency than the Medicago host race in terms of a longer penetration time and shorter duration times of phloem ingestion when fed on M. sativa. In contrast, few differences were found in the population abundance and feeding behavior of A. pisum between the two host races when fed on P. sativum. Meanwhile, of the nine candidate phenolic compounds, only genistein was significantly affected by aphid infestation; higher levels of genistein were detected in M. sativa after feeding by the Pisum host race, but these levels were reduced relative to uninfested controls after feeding by the Medicago host race, which suggested that genistein may be involved in the specialization of the aphid host race on M. sativa. Further exogenous application of genistein in artificial diets showed that the increase in genistein reduced the survival rate of the Pisum host race but had little effect on that of the Medicago host race. The transcriptomic profiles indicated that the transcripts of six genes with functions related to detoxification were up-regulated in the Pisum host race relative to the Medicago host race of A. pisum. These results suggested that the inducible plant phenolics and associated metabolic process in aphids resulted in their differential adaptations to their Fabaceae host

Temperature variability inferred from tree-ring records in Weichang region, China, and its teleconnection with large-scale climate forcing

Based on the combination of two dendrochronologies, the annual mean temperature from May to June for the last 160years was reconstructed in Weichang region, China, with the predictor variables accounting 43.3% of the variance during the calibration period of 1956-2012. Warm periods with temperature levels great than the mean (17.66 degrees C) occurred in 1853-1881, 1886-1891, 1904-1909, 1923-1930, 1964-1970, 1980-1988, 1998-2002 and 2007-2011; and cold periods with temperature levels less than the mean occurred in 1882-1885, 1892-1898, 1901-1903, 1910-1922, 1931-1963, 1971-1979, 1989-1997 and 2003-2006. The reconstruction showed that droughts usually occurred in the warm years. And the reconstructed temperature series showed an almost reverse trend to the total precipitation of previous August to present July from Chifeng-Weichang on inter-decadal scale, which indicate the basic feature of climate was warm-dry and cold-wet in Weichang region. The reconstructed temperature series showed a linear increasing trend with a rise 0.11 degrees C from 1880 to 2012. Comparisons with other temperature series revealed a consistently warming trend after the mid-1950s and confirmed a good repeatability and high reliability in our reconstruction. Spatial correlation implied the reconstruction could represent a regional temperature signal in the large parts of northern China and Central-Eastern Mongolia. The multi-taper method reveals several significant periodicities in our reconstruction over the past 160years, suggesting possible linkages with the El Nino-Southern Oscillation, lunar gravity, Pacific Decadal Oscillation (PDO) and solar activity. Correlation analysis between the reconstruction and Southern Oscillation Index (SOI), lunar geocentric declination, PDO and sunspot number further demonstrates that the temperature variations in Weichang region are negatively correlated with SOI and positively correlated with lunar gravity, PDO and solar activity in the long term

Tree-Ring-Based Drought Reconstruction in Northern North China over the Past Century

A tree-ring width chronology was developed from the Chinese pine (Pinus tabuliformis) in northern North China. To acquire a long-term perspective on the history of droughts in this region, the Standardized Precipitation Evapotranspiration Index (SPEI) from August of the previous year to February of the current year was reconstructed for the period of 1903-2012 AD. The reconstruction explained 46.6% of the instrumental records over the calibration period of 1952-2012. Five dry periods (1916-1927, 1962-1973, 1978-1991, 1994-1999 and 2002-2005) and three wet periods (1908-1915, 1928-1961 and 1974-1977) were found in the reconstructed period, and most of the dry years (periods) in the reconstruction were supported by historical records. Comparisons between the reconstruction and other nearby dryness/wetness indices and precipitation reconstructions demonstrated a good repeatability and high reliability in our reconstruction. Spatial correlation implied that the reconstruction could represent regional hydroclimatic characteristics on a larger regional scale. Significant periodicities and correlations were observed between the reconstructed data and the quasi-biennial oscillation (QBO), El Nino-Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO), which suggested that the hydroclimatic variation in northern North China may be closely connected to remote oceans. The significant and high correlation between the reconstructed series and sea surface temperatures (SSTs) in the eastern equatorial and Southeast Pacific Ocean indicated that ENSO may be the main factor influencing the regional climate

Kinetic Modeling of the Extraction–Oxidation Coupling Process for the Removal of Dibenzothiophene

Extraction–oxidation desulfurization (EODS) technology would be a potential industrial application for achieving ultralow-sulfur fuel oils. A combined extraction–oxidation system for dibenzothiophene removal from model fuel with H₂O₂ as an oxidant, acetonitrile as an extractant, and Mo/γ-Al₂O₃ as a catalyst was performed in a batch reactor. To study this complex heterogeneous system, the chemical reaction and mass transfer on each phase were individually assessed. Kinetics of the EODS system for dibenzothiophene in model fuel was developed, comprising the chemical kinetic mechanism and mass transfer effects. The kinetic parameters of the kinetic model, such as the kinetic constants and apparent activation energy, were determined. The EODS system in the experimental condition is determined by both the extraction process and catalytic oxidation reaction, because the terms involving the intrinsic resistance of the chemical reaction are no more important than mass transfer resistance

A novel gene REPTOR2 activates the autophagic degradation of wing disc in pea aphid

Wing dimorphism in insects is an evolutionarily adaptive trait to maximize insect fitness under various environments, by which the population could be balanced between dispersing and reproduction. Most studies concern the regulatory mechanisms underlying the stimulation of wing morph in aphids, but relatively little research addresses the molecular basis of wing loss. Here, we found that, while developing normally in winged-destined pea aphids, the wing disc in wingless-destined aphids degenerated 30-hr postbirth and that this degeneration was due to autophagy rather than apoptosis. Activation of autophagy in first instar nymphs reduced the proportion of winged aphids, and suppression of autophagy increased the proportion. REPTOR2, associated with TOR signaling pathway, was identified by RNA-seq as a differentially expressed gene between the two morphs with higher expression in the thorax of wingless-destined aphids. Further genetic analysis indicated that REPTOR2 could be a novel gene derived from a gene duplication event that occurred exclusively in pea aphids on autosome A1 but translocated to the sex chromosome. Knockdown of REPTOR2 reduced autophagy in the wing disc and increased the proportion of winged aphids. In agreement with REPTOR’s canonical negative regulatory role of TOR on autophagy, winged-destined aphids had higher TOR expression in the wing disc. Suppression of TOR activated autophagy of the wing disc and decreased the proportion of winged aphids, and vice versa. Co-suppression of TOR and REPTOR2 showed that dsREPTOR2 could mask the positive effect of dsTOR on autophagy, suggesting that REPTOR2 acted as a key regulator downstream of TOR in the signaling pathway. These results revealed that the TOR signaling pathway suppressed autophagic degradation of the wing disc in pea aphids by negatively regulating the expression of REPTOR2

Nutritional and physicochemical characteristics of purple sweet corn juice before and after boiling.

Sweet corn juice is becoming increasingly popular in China. In order to provide valuable health-related information to consumers, the nutritional and physicochemical characteristics of raw and boiled purple sweet corn juices were herein investigated. Sugars, antinutrients, total free phenols, anthocyanins, and antioxidant activity were analyzed by conventional chemical methods. The viscosity and stability of juices were determined by Ubbelohde viscosity meter and centrifugation, respectively. Boiling process could elevate viscosity, stability and sugar content, and reduce antinutrients, total free phenols, anthocyanins, and antioxidant activity in corn juice. In addition, short time boiling efficiently reduced the degradation of anthocyanins during subsequent refrigeration. The content of amino acids, vitamin B1/B2 and E were detected by High Performance Liquid Chromatography. Gas Chromatography Mass Spectrometry was used for the analysis of fatty acids and aroma compounds. Several aroma compounds not previously reported in corn were identified, including 1-heptanol, 2-methyl-2-butenal, (Z)-3-nonen-1-ol, 3-ethyl-2-methyl-1,3-hexadiene, and 2,4-bis(1,1-dimethylethyl)phenol. Interestingly, the boiling process had no apparent effect on the amino acids profile, but it caused a 45.8% loss of fatty acids in the juice by promoting the retention of fatty acids in the corn residue. These results provide detailed information that could be used for increasing consumers' knowledge of sweet corn juice, further development of sweet corn juice by food producers, and maize breeding programs