Peptidomics is a challenging field in which to create a link between genomic information and biological function through biochemical analysis of expressed peptides, including precise identification ...of post-translational modifications and proteolytic processing. We found that secreted peptides in Arabidopsis plants diffuse into the medium of whole-plant submerged cultures, and can be effectively identified by o-chlorophenol extraction followed by LC-MS analysis. Using this system, we first confirmed that a 12-amino-acid mature CLE44 peptide accumulated at a considerable level in the culture medium of transgenic plants overexpressing CLE44. Next, using an in silico approach, we identified a novel gene family encoding small secreted peptides that exhibit significant sequence similarity within the C-terminal short conserved domain. We determined that the mature peptide encoded by At1g47485, a member of this gene family, is a 15-amino-acid peptide containing two hydroxyproline residues derived from the conserved domain. This peptide, which we have named CEP1, is mainly expressed in the lateral root primordia and, when overexpressed or externally applied, significantly arrests root growth. CEP1 is a candidate for a novel peptide plant hormone.
Previous studies have revealed an association between the administration of α1-adrenoceptor blockers (α1Bs) and episodes of syncope in patients with benign prostatic hyperplasia (BPH). The objective ...of the present study was to evaluate the association between
α1Bs and syncope in BPH patients with hypertension using two different pharmacoepidemiological indices. Using the US Food and Drug Administration Adverse Event Reporting System, we analyzed the whole dataset and subsets for specific indications, including hypertension, diabetes, and
dyslipidemia, for males older than 40 years. The drugs of interest were alfuzosin, doxazosin, and terazosin as non-selective α1Bs and silodosin and tamsulosin as selective α1Bs. The reporting odds ratio (ROR) and information component (IC) were used for signal detection. The association
between the non-selective α1Bs and syncope was observed for all the items examined. The results obtained using the whole dataset, as well as the diabetes and dyslipidemia subsets, were same for the selective and non-selective α1Bs in terms of the association with syncope, while
no association with syncope was observed for both silodosin ROR: 1.09, 95% confidence interval (CI): 0.61-1.93; IC: 0.10, 95% CI: -0.72-0.92 and tamsulosin (ROR: 1.08, 95% CI: 0.90-1.30; IC: 0.10, 95% CI: -0.17-0.37) in patients with hypertension. The
data suggested that α1Bs, even those with receptor subtype selectivity, were associated with syncope. Thus, careful attention should be paid when prescribing α1Bs, especially to patients who do not take medications for hypertension.
Many case reports have been published concerning the development or exacerbation of psoriasis after administration of angiotensin-converting enzyme (ACE) inhibitors. The aim of the present study was ...to investigate the association between psoriasis and ACE inhibitors using the US Food
and Drug Administration Adverse Event Reporting System (FAERS) data. After excluding patients with psoriasis-related primary diseases, the association of psoriasis with 14 ACE inhibitors was examined using disproportional analyses reporting odds ratio (ROR) and information component (IC).
Signals were detected for all 14 ACE inhibitors combined (ROR: 1.25, 95% confidence interval CI: 1.14-1.37; IC: 0.31, 95% CI: 0.17-0.44) and individually for lisinopril (ROR: 1.20, 95% CI: 1.05-1.37; IC: 0.25, 95% CI: 0.06-0.45), perindopril (ROR: 1.86, 95% CI: 1.38-2.52;
IC: 0.86, 95% CI: 0.43-1.30), and ramipril (ROR: 1.63, 95% CI: 1.36-1.96; IC: 0.69, 95% CI: 0.42-0.96). ACE inhibitors are widely used in patients with hypertension, heart failure, and diabetes mellitus, which are considered comorbidities of psoriasis. Our results suggest
that the involvement of ACE inhibitors should be considered in patients on ACE inhibitor therapy who have developed (or show exacerbated) psoriasis.
The incidence of hyperglycemia and diabetes induced by everolimus has been shown in previous studies. Our study analyzed diabetes time-to-onset profiles after everolimus use in patients who underwent ...transplantation and patients with cancer. Using data from April 2007 to December 2018
in the Japanese Adverse Drug Event Report database, the reports with everolimus were classified according to its use as an immunosuppressant or anticancer drug. The median (25%-75%) days of diabetes time-to-onset in patients who underwent transplantation and patients with cancer were
172 (56-315) and 32 (18.5-57), respectively. There were no significant variations among patients with breast cancer, neuroendocrine tumor, and renal cell carcinoma. By conducting a Weibull shape parameter test, the lower limits of the 95% confidence intervals of the shape parameter
β values for the indications of the cancer types were >1, indicating the wear out failure type profile, whereas those for transplantation data indicated a random failure type profile. The diabetes time-to-onset profiles after everolimus use differed between usage as an anticancer drug
and immunosuppressant and there were no significant variations among the type of cancer. It was suggested that the incidence of diabetes should be monitored for 1-2 months in patients with cancer, whereas continuous monitoring is needed in patients who undergo transplantation.
This paper compares the experimental performance of three flux and speed observers for speed-sensorless induction motor drives and discusses the cause of their differences. The small signal analysis ...using the linearized model is carried out to analyze stability. Three methods are generally accepted to be representative candidates for high sensorless performance, namely: 1) rotor-flux model reference adaptive system (MRAS); 2) torque-current MRAS; and 3) adaptive nonlinear flux observer. Many other sensorless methods improved these methods. The paper discusses baseline conditions for the experiments and the stability analysis, which include matched load inertia, specified speed estimator dynamics, and sensorless operation within a speed control loop. For the comparison tests in the paper, the speed estimation dynamics of the methods are the same; this is important for parameter sensitivity. The paper concentrates on the low-speed performance, and all results shown are under sensorless speed control.
Summary
Primary biliary cholangitis (PBC) is characterized by the presence of serum anti‐mitochondrial autoantibodies (AMAs). To date, four antigens among the 2‐oxo‐acid dehydrogenase complex family, ...which commonly have lipoyl domains as an epitope, have been identified as AMA‐corresponding antigens (AMA‐antigens). It has recently been reported that AMAs react more strongly with certain chemically modified mimics than with the native lipoyl domains in AMA‐antigens. Moreover, high concentrations of circulating immune complexes (ICs) in PBC patients have been reported. However, the existence of ICs formed by AMAs and their antigens has not been reported to date. We hypothesized that AMAs and their antigens formed ICs in PBC sera, and analyzed sera of PBC and four autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic scleroderma, and rheumatoid arthritis) using immune complexome analysis, in which ICs are separated from serum and are identified by nano‐liquid chromatography‐tandem mass spectrometry. To correctly assign MS/MS spectra to peptide sequences, we used a protein‐search algorithm that including lipoylation and certain xenobiotic modifications. We found three AMA‐antigens, the E2 subunit of the pyruvate dehydrogenase complex (PDC‐E2), the E2 subunit of the 2‐oxo‐glutarate dehydrogenase complex (OGDC‐E2) and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation and xenobiotic modifications from PBC sera. Although the lipoylated sites of these peptides were different from the well‐known sites, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs. Further investigation of the lipoylated sites, xenobiotic modifications, and IC formation will lead to deepen our understanding of PBC pathogenesis.
Primary biliary cholangitis (PBC) is characterized by the presence of serum anti‐mitochondrial autoantibodies (AMAs) against the 2‐oxo‐acid dehydrogenase complex family; however, the immune complexes (ICs) formed by AMAs and the antigens has not been reported to date and their in vivo antigenicity is not fully clear. Immune complexome analysis identified three AMA‐antigens to be incorporated into ICs from PBC sera, the E2 subunit of the pyruvate dehydrogenase complex (PDC‐E2), the E2 subunit of the 2‐oxo‐glutarate dehydrogenase complex (OGDC‐E2), and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation or xenobiotic modifications. The lipoylated sites of these peptides were different from the well‐known sites; therefore, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs
Summary
Sjögren’s syndrome (SS) is a chronic autoimmune disease that mainly damages the salivary and lacrimal glands. Immune complex (IC) formation triggers local inflammation through IC deposition ...and decreased antigen function. Some ICs can leak from the lesion and into the saliva, but no salivary ICs have been reported to date. We used immune complexome analysis to comprehensively identify antigens incorporated into IC (IC‐antigens) in saliva samples from patients with SS (n = 9) or with xerostomia (n = 7). Neutrophil defensin 1 (67%), small proline‐rich protein 2D (67%), myeloperoxidase (44%), neutrophil elastase (44%), cathepsin G (33%), nuclear mitotic apparatus 1 (33%) and phosphatidylinositol 4‐phosphate 3‐kinase C2 domain‐containing subunit gamma (33%) were identified as new IC‐antigens specifically and frequently detected in the saliva of SS patients. Of these, neutrophil defensin 1, myeloperoxidase, neutrophil elastase and cathepsin G are neutrophil intracellular proteins, which suggests that repeated destruction of neutrophils due to abnormal autoimmunity may be involved in the pathogenesis of SS. We also analyzed serum samples from three SS patients. There was little overlap of IC‐antigens between two of the samples (fewer than 30% of the IC‐antigens in the saliva samples), suggesting that many ICs are formed locally and independently of the circulation. In addition, we found that four SS‐specific salivary antigens show sequence homology with several proteins of oral microbiomes but no antigen has homology with Epstein–Barr virus proteins. The homology between some IC‐antigens and oral microbiome proteins may indicate the impact of oral infection on local autoimmunity through molecular mimicry theory.
Immune complex (IC) formation can be directly pathogenic in autoimmune diseases; therefore, the identity of disease‐specific IC‐antigens in saliva may be important in Sjögren’s syndrome pathogenesis. We identified neutrophil intracellular proteins (neutrophil defensin 1, myeloperoxidase, neutrophil elastase and cathepsin G) as new IC‐antigens specifically and frequently detected in the patient saliva, which suggests that repeated destruction of neutrophils due to abnormal autoimmunity may be involved in the pathogenesis. In addition, there was little overlap of IC‐antigens between saliva and serum samples of a patient, suggesting that many ICs are formed locally and independently of the circulation.
Objectives
Recently, the use of saliva as a diagnostic tool has gained considerable attention because it is non‐invasive and easy to perform repeatedly. In this study, we focused on soluble molecules ...in saliva to establish a new diagnostic method for xerostomia.
Materials and Methods
Saliva was obtained from 90 patients with Sjögren's syndrome (SS), 22 patients with xerostomia associated with neurogenic/neuropsychiatric disorders and drugs (XND), 30 patients with radiation‐induced xerostomia (RX), and 36 healthy controls. Concentrations of helper T (Th) cytokines in saliva were measured by flow cytometric analysis. Concentrations of secretory IgA (SIgA) and chromogranin A (CgA) were measured by ELISA.
Results
Unstimulated and stimulated whole saliva from patients with SS, XND, and RX was significantly reduced compared with controls. Th1 and Th2 cytokines from SS patients were significantly higher than controls. Furthermore, Th2 cytokines were closely associated with strong lymphocytic accumulation in salivary glands from SS patients, while Th1 and Th17 cytokines were negatively associated. SIgA levels were not significantly different between all patient groups and controls. CgA levels from XND patients were significantly higher than controls.
Conclusions
The measurement of cytokines, CgA, and SIgA in saliva is suggested to be useful for the diagnosis of xerostomia and also to reveal disease status.
Ten household air–air heat pumps were used to heat an experimental greenhouse (
G
hp
) with a floor area of 151.2 m
2 at night in winter. The main objective is to investigate system coefficient of ...performance (COP). An estimation model was developed: 1) the energy balance analysis of another greenhouse (
G
oh
), identical and adjacent to the
G
hp
but with a conventional oil heater, was investigated synchronously, 2) based on the energy balance analysis, the heat transmission coefficient of the
G
oh
was estimated, 3) assuming the heat transmission coefficient was the same for both the
G
hp
and
G
oh
, the heat generated by the heat pumps was estimated, and 4) the COP was estimated as the ratio of heat generated to the electric energy consumed by the heat pumps. When the inside air temperature was kept at about 16 °C and the outside air temperature (
T
out
) ranged between −5 °C and 6 °C, the average hourly COP was 4.0, with a highest value of 5.8. Even when
T
out
< 0, the average hourly COP was 3.3, with the heat pumps defrosting asynchronously. The spatial distribution of air temperature in the
G
hp
was more uniform and its fluctuation with time was smaller than in the
G
oh
.
In the daytime, a CO₂ depletion of 10-15% and air circulation of less than 0.5ms⁻¹ often occur in a naturally ventilated greenhouse during a sunny day with high wind speed (3-5ms⁻¹). We, therefore, ...investigated the effects of moderate increase of the CO₂ concentration above the atmospheric level (500-600μmolmol⁻¹) and air circulation up to 1.0ms⁻¹ in a growth chamber on the net photosynthetic and transpiration rates of tomato seedlings as the first step. The average net photosynthetic rates were 2.1, 1.8, and 1.6 times higher in the growth chambers with increased CO₂ concentration (500-600μmolmol⁻¹) and air circulation (1.0ms⁻¹), increased CO₂ concentration, and increased air circulation, respectively, compared with those in the control (no increase in CO₂ concentration (200-300μmolmol⁻¹) or air circulation (0.3ms⁻¹). The transpiration rate increased with increased air circulation, while it decreased with increased CO₂ concentration regardless of air circulation. From the results, we consider that increasing the CO₂ concentration and/or air circulation in ventilated greenhouses up to the outside concentration (350-450μmolmol⁻¹) and 1.0ms⁻¹, respectively, can significantly increase the net photosynthetic rate of greenhouse plants.
PDF
