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Papaya has been reported to elicit IgE-mediated hypersensitivity via pollen inhalation and fruit consumption. Certain papaya sensitive patients with food allergy were found to experience recurrent respiratory distresses even after quitting the consumption of fruits. This observation prompted us to investigate the allergens commonly present in fruits and pollen grains of papaya. A discovery approach consisting of immunoproteomic detection followed by molecular characterization led to the identification of a novel papaya allergen designated as Cari p 1. This allergen was detected as a 56 kDa IgE-reactive protein from pollen as well as fruit proteome through serological analysis. The protein was identified as an endopolygalacturonase by tandem mass spectrometry. Full length Cari p 1 cDNA was isolated from papaya pollen, cloned in expression vector, and purified as recombinant allergen. The recombinant protein was monomeric and displayed pectinolytic activity. Recombinant Cari p 1 reacted with IgE-antibodies of all the papaya sensitized patient sera. In addition to IgE-reactivity, rCari p 1 displayed allergenic activity by stimulating histamine release from IgE-sensitized granulocytes. CD-spectroscopy of rCari p 1 revealed the presence of predominantly β-sheet characters. The melting curve of the allergen showed partial refolding from a fully denatured state indicating the possible presence of conformational IgE-epitopes characteristic of inhalant allergens in addition to the linear IgE-epitopes of food allergens. The expression of this allergen in papaya fruits was detected by immunoblot with anti-Cari p 1 rabbit IgG and reconfirmed by PCR. In an in vivo mouse model, rCari p 1 exhibited a comparable level of inflammatory responses in the lung and duodenum tissues explaining the dual role of Cari p 1 allergen in respiratory sensitization via pollen inhalation and sensitization of gut mucosa via fruit consumption. Purified rCari p 1 can be used a marker allergen for component-resolved molecular diagnosis. Further immunological studies on Cari p 1 are warranted to design immunotherapeutic vaccine for the clinical management of papaya allergy.
Coronary artery stenosis is the major pathological change of coronary heart disease (CHD). Within the framework of traditional Chinese medicine (TCM) theory, some kinds of TCM Zheng could exist in patients with CHD; accordingly, TCM practitioners could provide appropriate TCM therapy. However, little is known about the association between TCM Zheng and types of coronary artery stenosis. Such knowledge could help improve the accuracy and effectiveness of efforts to combine CHD treatment with TCM therapy. Therefore, the aim of this study is to determine the association between TCM Zheng and types of coronary artery stenosis.
Exoskeletons arise as the common ground between robotics and biomechanics, where rehabilitation is the main field in which these two disciplines find cohesion. One of the most relevant challenges in upper limb exoskeleton design relies in the high complexity of the human shoulder, where current devices implement elaborate systems only to emulate the drifting center of rotation of the shoulder joint. This paper proposes the use of 3D scanning vision technologies to ease the design process and its implementation on a variety of subjects, while a motion tracking system based on vision technologies is applied to assess the exoskeleton reachable workspace compared with an asymptomatic subject. Furthermore, the anatomic fitting index is proposed, which compares the anatomic workspace of the user with the exoskeleton workspace and provides insight into its features. This work proposes an exoskeleton architecture that considers the clavicle motion over the coronal plane whose workspace is determined by substituting the direct kinematics model with the dimensional parameters of the user. Simulations and numerical examples are used to validate the analytical results and to conciliate the experimental results provided by the vision tracking system.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by cytopenia and dysplasia. Anemia is the most common symptom in patients with MDS. Mitophagy and mitochondrial dysfunction might be involved in the development of MDS. In this study, we investigated the change of mitophagy in erythroid precursors in MDS patients. We found that NIX-mediated mitophagy was impaired in bone marrow nucleated red blood cells (NRBC) of MDS patients, associated with an increased amount of damaged mitochondria and increased ROS level which might lead to apoptosis and ineffective erythropoiesis. The results showed that the amount of mitochondria in GlycoA+ NRBC positively correlated with the count of ring sideroblasts in bone marrow samples. Meanwhile, the level of autophagy-associated marker LC3B in GlycoA+ NRBC had a positive correlation with hemoglobin (Hb) levels, and the amount of mitochondria in GlycoA+ NRBC had a negative correlation with Hb levels in high-risk MDS patients. Our results indicated that mitophagy might involve the pathogenesis of anemia associated with MDS. Autophagy might be a novel target in treatments of MDS patients.
Fenugreek (Trigonella foenum-graecum L.) is a well-known annual plant that is widely distributed worldwide and has possessed obvious hypoglycemic and hypercholesterolemia characteristics. In our previous study, three polyphenol stilbenes were separated from fenugreek seeds. Here, we investigated the effect of polyphenol stilbenes on adipogenesis and insulin resistance in 3T3-L1 adipocytes. Oil Red O staining and triglyceride assays showed that polyphenol stilbenes differently reduced lipid accumulation by suppressing the expression of adipocyte-specific proteins. In addition, polyphenol stilbenes improved the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) by promoting the phosphorylation of protein kinase B (AKT) and AMP-activated protein kinase (AMPK). In present studies, it was found that polyphenol stilbenes had the ability to scavenge reactive oxygen species (ROS). Results from adenosine triphosphate (ATP) production and mitochondrial membrane potentials suggested that mitochondria play a critical role in insulin resistance and related signaling activation, such as AKT and AMPK. Rhaponticin, one of the stilbenes from fenugreek, had the strongest activity among the three compounds in vitro. Future studies will focus on mitochondrial biogenesis and function.
Bacterial meningitis is an acute infectious inflammation of the protective membranes covering the brain. Its early diagnosis is vital because of its high morbidity and mortality. It is mostly diagnosed by a gold standard diagnostic tool i.e. Cerebrospinal Fluid (CSF) analysis. However, it is sometimes difficult and or impossible to do this procedure and an alternative diagnostic tool is needed. Contrast enhanced magnetic resonance imaging can detect the pus or other changes in subarachnoid space. But our optimal aim is to use an imaging method without using contrast to be useable and available in more specific condition.
Transcranial Direct Current Stimulation (tDCS) has been used as a non-invasive method to increase the plasticity of brain. Growing evidence has shown several brain disorders such as depression, anxiety disorders, and chronic pain syndrome are improved following tDCS. In patients with Obsessive-Compulsive Disorder (OCD), increased brain rhythm activity particularly in the frontal lobe has been reported in several studies using Eectroencephalogram (EEG). To our knowledge, no research has been done on the effects of electrical stimulation on brain signals of patients with OCD. We measured the electrical activity of the brain using EEG in patients with OCD before and after tDCS and compared it to normal participants.
Pathogenic Escherichia coli, one of the primary causes of urinary tract infections, has shown significant resistance to the most popular antibiotic, trimethoprim (TMP), which inhibits dihydrofolate reductase (DHFR). The resistance is modulated by single point mutations of DHFR. The impact of two clinically relevant mutations, P21L and W30R, on the activity of DHFR was evaluated via measurement of Michaelis-Menten and inhibitory kinetics, and structural characterization was undertaken by native mass spectrometry with ultraviolet photodissociation (UVPD). Compared to WT-DHFR, both P21L and W30R mutants produced less stable complexes with TMP in the presence of co-factor NADPH as evidenced by the relative abundances of complexes observed in ESI mass spectra. Moreover, based on variations in the fragmentation patterns obtained by UVPD mass spectrometry of binary and ternary DHFR complexes, notable structural changes were localized to the substrate binding pocket for W30R and to the M20 loop region as well as the C-terminal portion containing the essential G-H functional loop for the P21L mutant. The results suggest that the mutations confer resistance through distinctive mechanisms. A novel propargyl-linked antifolate compound 1038 was shown to be a reasonably effective inhibitor of the P21L mutant.
Spinal Cord Injury (SCI) causes interruption along the severed axonal tract(s) resulting in complete or partial loss of sensation and motor function. SCI can cause tetraplegia or paraplegia. Both these conditions can have lifelong excessive medical costs, as well as can reduce life expectancy. Preclinical research showed that Photobiomodulation therapy (PBMT), also known as Low-level laser (light) therapy (LLLT), possesses reparative and regenerative capabilities that have the potential to be used as a complimentary or supplementary SCI therapy. Despite the promising effects of PBMT, there are still no standardized irradiation parameters (i.e. different wavelengths, power, fluence, irradiance, beam type, beam diameters, and irradiation time) and there is also a lack of standardized experimental protocol(s), which makes it difficult to compare different studies. It is, nonetheless, essential to standardize such irradiation parameters in order to provide better PBMTs. The aim of this study, therefore, is to evaluate the delivery of light in a 3D voxelated SCI rat model for PBMT using different irradiation parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat beam; and beam diameters: 0.04-1.2 cm) using Monte Carlo simulation. This study also aids in providing standardization for preclinical research for PBMT, which will eventually translate into clinical standardization upon clinical research studies and results.
A fossil whale from the Hikatagawa Formation (Middle Miocene, 15.2-11.5 Ma) of Hokkaido, Japan is described as a new genus and species Taikicetus inouei and its phylogenetic position is examined. Consistent with the result of Marx, Lambert & de Muizon (2017), the Cetotheriidae form a clade with the Balaenopteroidea, and "a clade comprising Isanacetus, Parietobalaena and related taxa" is located basal to the Balaenopteroidea + Cetotheriidae clade. Taikicetus inouei is placed in the clade with most of members of "Cetotheres" sensu lato comprising Isanacetus, Parietobalaena and related taxa. Taikicetus inouei can be distinguished from the other members of "Cetotheres" sensu lato in having an anteriorly swollen short zygomatic process, high triangular coronoid process, and angular process, which does not reach as far posterior as the mandibular condyle. Taikicetus inouei is only record of "Cetotheres" sensu lato from Hokkaido, Japan and the northern-most records of "Cetotheres" sensu lato in Japan.
Strawberry (Fragaria × ananassa) is an ideal plant for fruit development and ripening research due to the rapid substantial changes in fruit color, aroma, taste, and softening. To gain deeper insights into the genes that play a central regulatory role in strawberry fruit development and ripening characteristics, transcriptome profiling was performed for the large green fruit, white fruit, turning fruit, and red fruit stages of strawberry. A total of 6,608 differentially expressed genes (DEGs) with 2,643 up-regulated and 3,965 down-regulated genes were identified in the fruit development and ripening process. The DEGs related to fruit flavonoid biosynthesis, starch and sucrose biosynthesis, the citrate cycle, and cell-wall modification enzymes played important roles in the fruit development and ripening process. Particularly, some candidate genes related to the ubiquitin mediated proteolysis pathway and MADS-box were confirmed to be involved in fruit development and ripening according to their possible regulatory functions. A total of five ubiquitin-conjugating enzymes and 10 MADS-box transcription factors were differentially expressed between the four fruit ripening stages. The expression levels of DEGs relating to color, aroma, taste, and softening of fruit were confirmed by quantitative real-time polymerase chain reaction. Our study provides important insights into the complicated regulatory mechanism underlying the fruit ripening characteristics in Fragaria × ananassa.
Rongcheng Bay is a coastal bay of the Northern Yellow Sea, China. To investigate and monitor the fish resources in Rongcheng Bay, 187 specimens from 41 different species belonging to 28 families in nine orders were DNA-barcoded using the mitochondrial cytochrome c oxidase subunit I gene (COI). Most of the fish species could be discriminated using this COI sequence with the exception of Cynoglossus joyneri and Cynoglossus lighti. The average GC% content of the 41 fish species was 47.3%. The average Kimura 2-parameter genetic distances within the species, genera, families, and orders were 0.21%, 5.28%, 21.30%, and 23.63%, respectively. Our results confirmed that the use of combined morphological and DNA barcoding identification methods facilitated fish species identification in Rongcheng Bay, and also established a reliable DNA barcode reference library for these fish. DNA barcodes will contribute to future efforts to achieve better monitoring, conservation, and management of fisheries in this area.
Low-cost phenotyping using proximal sensors is increasingly becoming popular in plant breeding. As these techniques generate a large amount of data, analysis pipelines that do not require expertise in computer programming can benefit a broader user base. In this work, a new online tool Specalyzer is presented that allows interactive analysis of the spectral reflectance data generated by proximal spectroradiometers. Specalyzer can be operated from any web browser allowing data uploading, analysis, interactive plots and exporting by point and click using a simple graphical user interface. Specalyzer is evaluated with case study data from a winter wheat fertilizer trial with two fertilizer treatments. Specalyzer can be accessed online at http://www.specalyzer.org.
Litter decomposition is a key process in the functioning of forest ecosystems, because it strongly controls nutrient recycling and soil fertility maintenance. The interaction between the litter chemical composition and the metabolism of the soil microbial community has been described as the main factor of the decomposition process based on three hypotheses: substrate-matrix interaction (SMI), functional breadth (FB) and home-field advantage (HFA). The objective of the present study was to evaluate the effect of leaf litter quality (as a direct plant effect, SMI hypothesis), the metabolic capacity of the microbial community (as a legacy effect, FB hypothesis), and the coupling between the litter quality and microbial activity (HFA hypothesis) on the litter decomposition of two contiguous deciduous oak species at a local scale.
Depressive disorders (DD) are known to be associated with increased DNA damage, the impairment of DNA damage repair, and the presence of single-nucleotide polymorphisms (SNPs) in DNA damage repair genes. Some indirect evidence also suggests that uracil metabolism may be disrupted in depressed patients. Therefore, the current study genotypes three SNPs localized in genes encoding uracil-processing proteins: two glycosylases, i.e., UNG g.7245G>C (rs34259), SMUG1 c.-31A>G (rs3087404), and dUTPase, i.e., DUT g.48638795G>T (rs4775748). The polymorphisms were analyzed in 585 DNA samples (282 cases and 303 controls) using TaqMan probes. The G/G genotype and G allele of UNG polymorphism decreased the risk of depression, while the G/C genotype and C allele of the same SNP increased it. It was also found that G/G carriers had their first episode significantly later than the heterozygotes. Although there was no association between the occurrence of depression and the SMUG1 SNP, a significant difference was found between the homozygotes regarding the onset of DD. In conclusion, the SNPs localized in the uracil-processing genes may modulate the occurrence and the onset of depression, which further supports the hypothesis that impairment of DNA damage repair, especially base-excision repair, may play an important role in the pathogenesis of the disease.
Metabarcoding is a popular application which warrants continued methods optimization. To maximize barcoding inferences, hierarchy-based sequence classification methods are increasingly common. We present methods for the construction and curation of a database designed for hierarchical classification of a 157 bp barcoding region of the arthropod cytochrome c oxidase subunit I (COI) locus. We produced a comprehensive arthropod COI amplicon dataset including annotated arthropod COI sequences and COI sequences extracted from arthropod whole mitochondrion genomes, the latter of which provided the only source of representation for Zoraptera, Callipodida and Holothyrida. The database contains extracted sequences of the target amplicon from all major arthropod clades, including all insect orders, all arthropod classes and Onychophora, Tardigrada and Mollusca outgroups. During curation, we extracted the COI region of interest from approximately 81 percent of the input sequences, corresponding to 73 percent of the genus-level diversity found in the input data. Further, our analysis revealed a high degree of sequence redundancy within the NCBI nucleotide database, with a mean of approximately 11 sequence entries per species in the input data. The curated, low-redundancy database is included in the Metaxa2 sequence classification software (http://microbiology.se/software/metaxa2/). Using this database with the Metaxa2 classifier, we performed a cross-validation analysis to characterize the relationship between the Metaxa2 reliability score, an estimate of classification confidence, and classification error probability. We used this analysis to select a reliability score threshold which minimized error. We then estimated classification sensitivity, false discovery rate and overclassification, the propensity to classify sequences from taxa not represented in the reference database. Our work will help researchers design and evaluate classification databases and conduct metabarcoding on arthropods and alternate taxa.
Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice.
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