A new clade, Trichoderma formosa, secretes eliciting plant response-like 1 (Epl1), a small peptide elicitor that stimulates plant immunity. Nicotiana benthamiana pretreated with Epl1 for 3 days ...developed immunity against Tomato mosaic virus (ToMV) infection. The transcriptome profiles of T. formosa and N. benthamiana were obtained by deep sequencing; the transcript of Epl1 is 736 nt in length and encodes a 12-kDa peptide. Identifying critical genes in Epl1-mediated immunity was challenging due to high similarity between the transcriptome expression profiles of Epl1-treated and ToMV-infected N. benthamiana samples. Therefore, an efficient bioinformatics data mining approach was used for high-throughput transcriptomic assays in this study. We integrated gene-to-gene network analysis into the ContigViews transcriptome database, and genes related to jasmonic acid and ethylene signaling, salicylic acid signaling, leucine-rich repeats, transcription factors, and histone variants were hubs in the gene-to-gene networks. In this study, the Epl1 of T. formosa triggers plant immunity against various pathogen infections. Moreover, we demonstrated that high-throughput data mining and gene-to-gene network analysis can be used to identify critical candidate genes for further studies on the mechanisms of plant immunity.
Abstract
Background
CAB+RPV LA is the only complete long-acting regimen for treatment of virologically suppressed PWH. Administered monthly or every 2 months by a healthcare provider, CAB+RPV LA may ...alleviate adherence challenges with daily oral therapy. The ABOVE study evaluated real-world adherence and persistence to CAB+RPV LA versus remaining on oral ART regimens.
Methods
ABOVE was a retrospective US cohort study using Symphony Health Solutions Integrated Dataverse administrative claims database from 01/01/2020 to 12/31/2022. PWH ≥12 years of age on stable guideline-recommended oral ART were categorized into those initiating CAB+RPV LA and those remaining on oral ART. Index date was defined as first injection between 01/01/2021 and 6/30/2022 (CAB+RPV LA cohort) or imputed for the oral ART cohort. PWH were required to have ≥6 months of follow-up after index. Standardized mortality ratio (SMR) weights were generated based on propensity scores to balance baseline characteristics between cohorts. Adherence (proportion of days covered (PDC) ≥0.9 over 6-months following index) and persistence to the index regimen (days from index to the earliest of treatment discontinuation or end of follow-up) were compared. Logistic regression model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for adherence.
Results
393,484 PWH were identified during the study period. After applying eligibility criteria, 130,362 in the oral ART cohort (N=950 after weighting) and 947 in the CAB+RPV LA cohort comprised the analysis sample. Key baseline characteristics were balanced post SMR weighting (Table 1). Majority of CAB+RPV LA dosing was every two months only (50%) or switched from monthly to every two months (33%). A higher proportion of PWH in the CAB+RPV LA cohort were adherent (72% vs 43%, p< 0.001) and had higher persistence (274 vs 256 days, p< 0.001) compared with the oral ART cohort (Table 2). PWH in the CAB+RPV LA cohort had significantly higher adjusted odds of being adherent compared to the oral ART cohort (OR: 4.43, 95% CI: 2.38, 8.24, p< 0.001).
Conclusion
These data demonstrate that, among US PWH on stable oral ART, switching to long-acting ART resulted in significantly higher adherence and persistence, a critical aspect of long-term success of HIV treatment, compared with remaining on oral ART.
Disclosures
Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee Raj Desai, PhD, Analysis Group, Inc: Employment|ViiV Healthcare: Grant/Research Support Rose Chang, ScD, Analysis Group, Inc.: Employee|ViiV Healthcare: Grant/Research Support Louise Clear, MPH, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Zhuo Chen, MPH, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Daisy Liu, MS, Analysis Group, Inc.: Employment|ViiV Healthcare: Grant/Research Support Maral DerSarkissian, PhD, Analysis Group, Inc: Employment|ViiV Healthcare: Grant/Research Support Paula Teichner, PharmD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Edgar T. Overton, MD, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds
The coefficient of intrinsic dependence (CID) is capable of determining associations among variables without making distributional or functional assumptions regarding random variables. In this study, ...we developed the partial coefficient of intrinsic dependence (pCID) to facilitate the step-by-step selection of variables that are relevant to a target variable. The strategy of selecting relevant variables using the CID along with the pCID can eliminate interference from other relevant variables. From simulation results, we observed that the proposed method is more sensitive to curvilinearity and more specific to linearity than the combination of Pearsons correlation coefficient and the partial correlation coefficient (PCC/pPCC). This property may provide the opportunity to index different levels of curvilinearity according to CID/pCID outcomes. In practice trials conducted using publicly available microarray data, the CID/pCID procedure successfully identified cold-responsive genes related to three C-repeat binding factors, and was especially effective at identifying some sample-specific gene-gene interactions. Therefore, the proposed strategy may be beneficial in meta-analysis to distinguish general forms of relationships from the noise.
Histiocytic sarcoma of the eyelid Liu, Daisy Jiayi; Rullo, Jacob; Kratky, Vladimir ...
Saudi journal of ophthalmology,
07/2019, Letnik:
33, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Histiocytic Sarcoma is a rare malignant hematopoietic neoplasm that can present in extranodal sites including lymph nodes, skin, gastrointestinal tract, and the central nervous system. Only 10% of ...cases manifest as skin lesions and very few are reported in the head and neck. The authors report a case of histiocytic sarcoma of the eyelid in a 72-year-old male that was clinically diagnosed as a chalazion. Initial excision was not sent for routine histopathological assessment and the patient was subsequently lost to follow up. Recurrence occurred at the eyelid site and additional lesions were found on the forearms, abdomen, and right knee. Histopathological assessment of one of these other sites confirmed the diagnosis of histiocytic sarcoma. To our knowledge, this is the first reported case of disseminated histiocytic sarcoma that originally presented in the ocular adnexa (eyelid). And, as the initial lesion was not sent to Pathology and therefore potentially missed, this case highlights the importance of submitting tissue, including chalazia, for pathologic evaluation.
Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass ...in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa (low, median, and high tertile). PA patients with medium tertile of UNa had significant lower LVMI than the other two groups (LVMI: 144.1 ± 42.9, 121.1 ± 33.4, and 136.7 ± 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of variance p=0.006, post-hoc p <0.05). Multifactor analysis of variance confirmed this finding after adjustment for clinical parameters. Post-hoc analyses revealed that the high UNa tertile was associated with higher left ventricular end-diastolic volume compared with medium UNa tertile; while the low UNa tertile was associated with higher mean wall thickness compared with medium UNa tertile. The findings imply the reasons for increased LVMI may be different in patients with the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour UNa is associated with lowest LVMI in patients with PA.
Abstract Background Ventricular remodeling following myocardial infarction (MI) is closely associated with cyclooxygenase-2 (COX-2) expression. 5-methoxytryptophan (5-MTP) was reported to control ...COX-2 expression. Objectives To investigate the association between 5-MTP and post-MI left ventricular remodeling. Methods This prospective study enrolled 26 non-diabetic patients with first-time ST segment elevation myocardial infarction (STEMI), and 58 controls. Levels of 5-MTP, N-terminal of pro-brain natriuretic peptide (NT-proBNP), aminoterminal propeptide of type III procollagen, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 were measured at day 1, day 3, 3 months, 6 months, and 1 year post-MI. Echocardiography was performed during the acute stage (within 72 h) and 3 months, 6 months, and 1 year post-MI. Results The STEMI patients had a significantly lower plasma 5-MTP level at day 1 which reached a nadir at 3 months post-MI. The level of 5-MTP at day 3 post-MI was significantly correlated with the level of NT-proBNP 1 year post-MI, suggesting that the level of plasma 5-MTP in the early phase after MI may predict subsequent cardiac stress and failure. Receiver operating characteristic curve analysis revealed that plasma 5-MTP had the best area under the curve value to predict plasma NT-proBNP 1 year post-MI. Further analysis using net reclassification improvement and integrated discrimination improvement models confirmed that plasma 5-MTP at day 3 post-MI significantly improved the predictive power of each of the parameters. Conclusion In non-diabetic STEMI patients, plasma 5-MTP levels were associated with biomarkers of post-MI left ventricular remodeling and damage.
In exonization events, Ds1 may provide donor and/or acceptor sites for splicing after inserting into genes and be incorporated into new transcripts with new exon(s). In this study, the protein ...variants of Ds1 exonization yielding additional functional profile(s) were studied. Unlike Ds exonization, which creates new profiles mostly by incorporating flanking intron sequences with the Ds message, Ds1 exonization additionally creates new profiles through the presence or absence of Ds1 messages. The number of unique functional profiles harboring Ds1 messages is 1.3-fold more than that of functional profiles without Ds1 messages. The highly similar 11 protein isoforms at a single insertion site also contribute to proteome complexity enrichment by exclusively creating new profiles. Particularly, Ds1 exonization produces 459 unique profiles, of which 129 cannot be built by Ds . We thus conclude that Ds and Ds1 are independent but synergistic in their capacity to enrich proteome complexity through exonization.
Background
Exonization is an event which an intronic transposed element (TE) provides splice sites and leads to alternatively spliced cassette exons. Without disrupting of the inserted gene’s ...function, TEs can expand the proteome diversity by adding the splice variant that encodes a different, yet functional protein. Previously, we found that the main contribution of
Ds
exonization for gene divergence is not providing genetic messages but incorporating the intron sequences with different reading frame patterns to enrich the plant proteome.
Ds1
, another member of
Ac
/
Ds
transposon system, differs from
Ds
by providing 3 splice donor sites and 2 acceptor sites for alternative splicing, which may greatly increase the extent for proteome expansion.
Results
In this study, we performed a genome-wide survey of
Ds1
exonization events to assess its extent to enrich proteomes in plants. Each
Ds1
insertion yielded 11 transcript isoforms by integrating the splice donor and/or acceptor sites, which composed a bulk of all exonized transcript orthologs from the dicot
Arabidopsis thaliana
and the monocot
Oryza sativa
(rice). The exonized transcripts were analyzed by the locations of the termination codon (PTC) and the putative targets for the nonsense-mediated decay (NMD) pathway were then excluded. Compared with the
Ds
element,
Ds1
harbors more contents of non-NMD transcripts for protein isoforms.
Conclusions
The contribution of
Ds1
exonization for gene divergence is incorporating the intron sequences with different reading frame patterns to enrich the plant proteome. All these simulation results direct new experimental analysis at the molecular level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fibroblast growth factor-23 (FGF-23), a novel marker of bone disease in chronic kidney disease (CKD) has been shown to correlate with vascular calcifications. We aimed to describe the effect of the ...calcium phosphate product (Ca*P) on FGF-23 concentrations in children and young adults without confounding cardiovascular disease.
Pediatric and young adult patients with CKD stages I-V were recruited in this cross sectional study to measure FGF-23, cystatin C, vitamin D-metabolites and other serum markers of bone metabolism. FGF-23 levels were determined with an enzyme-linked immunosorbent assay. The association between FGF-23 and (Ca*P) was assessed using non-parametric methods. Patients were divided into two age groups, less than 13 years of age and greater than 13 years of age.
This cross-sectional study measured serum FGF-23, in 81 patients (42 females, 51.9%) at London Health Sciences Centre, aged 2 to 25 years, with various stages of CKD (Cystatin C estimated glomerular filtration rate, eGFR=10.7-213.0 ml/min). For the whole entire group of patients, FGF-23 levels were found to correlate significantly with age (Spearman r= 0.26, p=0.0198), Cystatin C eGFR (Spearman r=-0.40 p=0.0002), CKD stage (Spearman r=0.457, p<0.0001), PTH (Spearman r=0.330, p=0.0039), ionized calcium (Spearman r=-0.330, p=0.0049), CysC (Spearman r= 0.404, p=0.0002) and 1,25-dihydroxyvitamin D (Spearman r=-0.345, p=0.0034) concentrations. No significant correlation was found between FGF-23 levels and calcium phosphate product (Spearman r= 0.164, p=0.142). Upon classification of patients into two age groups, less than 13 years of age and more than 13 years of age, correlational results differed significantly. FGF-23 correlated with CysC eGFR( Spearman r= -0.633, p<0.0001), CKD stage (Spearman r=0.731, p<0.0001), phosphate (Spearman r= 0.557, p<0.0001), calcium phosphate product (Spearman r=0.534, p<0.0001), 125(OH)2 Vit D (Spearman r=-0.631, p<0.0001), PTH (Spearman r= 0.475, p=0.0017) and ionized calcium (Spearman r= -0.503, p=0.0015) only in the older group. The relationship between FGF-23 and Ca*P for the older group could be expressed by the exponential model FGF-23= 38.15 e0.4625Ca*P.
Abnormal values of FGF-23 in adolescents and young adults with CKD correlate with Ca* P in the absence of vascular calcifications, and may serve as a biomarker for the risk of cardiovascular calcifications.
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