Insertion of transposable elements (TEs) into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization which can enrich the complexity of ...transcriptomes and proteomes. Previously, we performed the first experimental assessment of TE exonization by inserting a Ds element into each intron of the rice epsps gene. Exonization of Ds in plants was biased toward providing splice donor sites from the beginning of the inserted Ds sequence. Additionally, Ds inserted in the reverse direction resulted in a continuous splice donor consensus region by offering 4 donor sites in the same intron. The current study involved genome-wide computational analysis of Ds exonization events in the dicot Arabidopsis thaliana and the monocot Oryza sativa (rice). Up to 71% of the exonized transcripts were putative targets for the nonsense-mediated decay (NMD) pathway. The insertion patterns of Ds and the polymorphic splice donor sites increased the transcripts and subsequent protein isoforms. Protein isoforms contain protein sequence due to unspliced intron-TE region and/or a shift of the reading frame. The number of interior protein isoforms would be twice that of C-terminal isoforms, on average. TE exonization provides a promising way for functional expansion of the plant proteome.
To evaluate the ultrasound biomicroscopic characteristics of primary iridociliary cysts presenting to a Canadian tertiary care centre.
Retrospective study.
A total of 189 patients (212 eyes) referred ...to the Sinai Health System (Toronto) for suspected iris abnormalities.
Clinical records of patients referred between March 2016 and October 2019 were reviewed. All patients were evaluated and received a diagnosis of an iridociliary cyst using ultrasound biomicroscopy (UBM). Data were collected for age, sex, involvement (iris vs ciliary body), laterality, size, and location on initial examination and subsequent follow-up.
Of the 189 patients (212 eyes) with iridociliary cysts, more were female (65.1%) versus male (34.9%). The highest incidence occurred in females aged 21–30 years (13.2%). The iris pigment epithelium was involved in 84.4%, and only the ciliary body was involved in 3.8%. Both the iris pigment epithelium and the ciliary body were involved in 10.8%. The size of the cysts ranged between 0.5 and 4.41 mm in diameter. Cysts greater than 1 mm in diameter occurred in 78.7%, and 86.8% of cysts occurred unilaterally. Twelve percent were multicystic, and 8.5% were multiloculated, with 1% exhibiting both features. Twenty-three eyes (12.2%) were reviewed at 1 year of follow-up with UBM. Stable iridociliary cysts with no appreciable change in size were seen in 73.9% (n = 17). Iridociliary cyst growth was noted at 4 months in 1 patient.
Information regarding iridociliary cysts is not easily available in the literature. UBM is a helpful clinical tool in the evaluation of iris abnormalities. Iridociliary cysts tend to be stable and compatible with a low rate of complications.
Présenter les caractéristiques des kystes irido-ciliaires primaires à l’échographie biomicroscopique dans un centre de soins tertiaires du Canada.
Étude rétrospective.
Au total, 189 patients (212 yeux) ont été adressés au Sinai Health System (Toronto) en raison d'une suspicion d'anomalies de l'iris.
On a examiné les dossiers médicaux des patients qui nous ont été adressés entre mars 2016 et octobre 2019. Tous les patients ont été évalués par échographie biomicroscopique et ont reçu un diagnostic de kyste irido-ciliaire. Les données sur l’âge, le sexe, l'atteinte (iris vs corps ciliaire), la latéralité du kyste, sa taille et sa localisation ont été notées lors de l'examen initial et du suivi.
Parmi les 189 patients (212 yeux) qui présentaient un kyste irido-ciliaire, les femmes (65,1 %) étaient plus nombreuses que les hommes (34,9 %). L'incidence la plus élevée a été enregistrée chez les femmes de 21 à 30 ans (13,2 %). L’épithélium pigmentaire de l'iris était touché dans 84,4 % des cas, et seul le corps ciliaire était atteint dans 3,8 % des cas. Le kyste touchait à la fois l’épithélium pigmentaire de l'iris et le corps ciliaire dans 10,8 % des cas. Le diamètre des kystes s’échelonnait de 0,5 à 4,41 mm et dépassait 1 mm dans 78,7 % des cas; 86,8 % des kystes étaient unilatéraux. On comptait 12 % de polykystose, tandis que 8,5 % des kystes étaient multiloculaires; 1 % des kystes présentaient ces deux caractéristiques. Vingt-trois (23) yeux (12,2 %) ont fait l'objet d'une échographie biomicroscopique 1 an plus tard. La taille des kystes irido-ciliaires était demeurée stable, et ces derniers n'avaient pour ainsi dire pas pris de volume dans 73,9 % des cas (n = 17). Cependant, on a observé une augmentation de la taille du kyste irido-ciliaire chez 1 patient après 4 mois.
On trouve peu de données sur les kystes irido-ciliaires dans la littérature médicale. L’échographie biomicroscopique est un outil clinique utile pour évaluer les anomalies de l'iris. Les kystes irido-ciliaires ont tendance à demeurer stables au fil du temps et à entraîner peu de complications.
To describe the steps, hurdles, and recommendations for implementation of the immediately sequential bilateral cataract surgery (ISBCS) evidence-based protocol at a high-volume Canadian tertiary care ...centre.
Quality-improvement study.
A total of 406 patients who underwent ISBCS from July 2020 to December 2020. Patients were selected based on specific inclusion and exclusion criteria including psychosocial factors, refractive error and consent. This initiative impacted staff at all levels involved with cataract surgery.
The Model of Improvement framework was used and involved numerous discussions with multidisciplinary teams of ophthalmologists, nursing and support staff, management, pharmacists, and medical device reprocessing teams. This initiative was created and refined via a thorough review of the literature and current best practices. It was implemented in July 2020 after a nursing “huddle.” Any adverse outcomes and overall impact were collected from various levels of staff involved.
Each eye was treated as a separate surgery with a double time-out per bilateral case. Additional measures were taken to ensure different lot numbers for medications, equipment, and materials. This practice increased surgical volume by approximately 25% and reduced the number of patient visits by 50%, reducing potential COVID-19 exposure.
The resulting protocol from our study may be useful to other centres wishing to integrate ISBCS as one example of successful implementation. Of the 406 cases of ISBCS performed, we report zero cases of toxic anterior segment syndrome or endophthalmitis. In times of decreased elective surgeries, ISBCS is a safe and effective option to supplement surgical volume and provide significant patient benefits.
Décrire les étapes, les obstacles et les recommandations en vue de l'implantation d'un protocole factuel en matière de chirurgie de la cataracte bilatérale immédiatement séquentielle (CCBIS) dans un centre de soins tertiaires traitant un grand nombre de patients au Canada.
Étude d'amélioration de la qualité.
Un total de 406 patients qui ont subi une CCBIS entre juillet 2020 et décembre 2020 ont été choisis en fonction de critères d'inclusion et d'exclusion spécifiques, dont les facteurs psychosociaux, l'erreur de réfraction et le consentement. Ce projet faisait appel à l'ensemble du personnel concerné par la chirurgie de la cataracte.
Nous avons eu recours à un modèle d'amélioration de la qualité et tenu de nombreuses discussions avec des équipes multidisciplinaires formées d'ophtalmologistes, de membres du personnel infirmier, du personnel de soutien et de la direction, de pharmaciens et de personnes chargées du retraitement des dispositifs médicaux. Le projet a été créé et mis au point après un examen approfondi de la littérature et des meilleures pratiques actuelles. Il a été implanté en juillet 2020 à la suite d'une « réunion en petit comité » du personnel infirmier. Tous les intervenants ont fourni des données sur les résultats indésirables et les répercussions globales du projet.
Chaque œil a été traité comme intervention chirurgicale distincte et s'accompagnait d'une pause chirurgicale distincte, donc deux pauses par cas bilatéral. Des mesures supplémentaires ont été prises pour s'assurer que les médicaments, l’équipement et le matériel provenaient tous de lots différents, ce qui a augmenté le volume chirurgical d'environ 25 % et réduit le nombre de visites des patients de 50 %, d'où une atténuation de l'exposition éventuelle à la COVID-19.
Le protocole issu de notre étude peut servir d'exemple d'implantation réussie pour d'autres centres qui souhaitent intégrer la CCBIS. Lors des 406 instances de CCBIS, nous n'avons recensé aucun cas de syndrome du segment antérieur toxique ni d'endophtalmie. Dans un contexte de réduction du nombre de chirurgies non urgentes, la CCBIS représente une option sûre et efficace pour augmenter le volume chirurgical et offrir aux patients des avantages significatifs.
Approximately half of all energy consumed is used for generating heat and hot water in the UK, meanwhile, space heating and hot water consist of about 21% of greenhouse gas emissions. One pathway of ...decarbonizing heat is electrification of heat, the requirement of electricity is then met through smart grid and demand side response management. A new method for electrifying heat through a balanced energy network (BEN) system, which is situated in central campus of London South Bank University, has been presented. The validations of BEN model are performed against historic measurement data and manufacturer performance data. BEN system performance is then predicted and evaluated through investigating the effects of BEN and building internal factors including system operation mode, thermal storage, indoor set-point temperature, and COP of heat pump. Several key results were drawn as follows: (1) Carbon emissions from building energy consumption mainly depend on operation mode and thermal storage capacity of BEN system, actual heat demand in buildings and carbon emission factor as a function of time; (2) Energy consumption and costs and its carbon emissions will nonlinearly increase with the increasing of indoor set-point temperature; (3) In January (the coldest month of the year), the heating consumption for operating BEN system will be decreased by 77.9%/72.9% compared with historic monitoring data of 2014/2015; (4) For BEN system, the usage, costs and carbon emissions of electricity supplying to heat pump is an decreasing function of COP.
•Prediction & Evaluation on system performance for a Balanced Energy Network in London.•BEN system performance jointly solved by measurements and simulations.•Diverse effects of internal factors of BEN & Buildings on system performance.•Carbon emissions depending on operation mode, thermal storage capacity & real heat demand.•Heating consumption decreased by 77.9%/72.9% for BEN comparing to 2014/2015 data.
We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(–) breast cancer population via network approach. STAT3 ...is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN.
Summary Objective G-protein-coupled receptor 30 (GPR30) has been reported to be a novel estrogen receptor a (ERa) in vitro . Therefore, the interactions among GPR30, ERa, progesterone receptor (PR) ...and human epidermal growth factor receptor-2 (HER-2/neu), and their prognostic utilities in the infiltrating ductal carcinoma (IDC) of the breast were evaluated. Materials and Methods Messenger RNA (mRNA) levels of GPR30, ERa, PR and HER-2/neu in the tumor samples of 118 Taiwanese IDC patients and 27 non-tumor mammary tissues were measured via quantitative polymerase chain reaction analyses. The correlations of GPR30 mRNA levels with clinical parameters, i.e. tumor/non-tumor, ERa, PR, HER-2/neu, age, lymph node metastasis, lymph–vascular invasion, grade, stage and patient survival, were assessed by using appropriate statistical analyses. Results GPR30 expression was observed to be lower in IDC ( p < 0.001) than in non-tumor mammary tissues. Importantly, GPR30 mRNA level was positively correlated with that of ERa ( p = 0.001) and PR ( p = 0.001) but not correlated with that of HER-2/neu when they were analyzed as continuous variables. However, lower GPR30 was noticed in tumors with HER-2/neu protein overexpression. GPR30 expression was not correlated with age, lymph node metastasis, lymph–vascular invasion, grade and stage in IDC. GPR30 expression was not an independent prognostic factor for patient survival. Conclusion GPR30 expression is downregulated in IDC. GPR30 is preferentially co-expressed with ER and/or PR but is lowly expressed in HER-2/neu(+) tumors. The correlation of GPR30 expression with clinical parameters, including patient survival, was not evident in this cohort.
A PHYL1 effector protein interferes with miR396-mediated transcriptional regulator mRNA decay, enhancing the transcription factor for abnormal flower development.
Leafy flowers are the major symptoms ...of peanut witches’ broom (
PnWB
) phytoplasma infection in
Catharanthus roseus
. The orthologs of the phyllody symptoms1 (PHYL1) effector of
PnWB
from other species of phytoplasma can trigger the proteasomal degradation of several MADS box transcription factors, resulting in leafy flower formation. In contrast, the flowering negative regulator gene
SHORT VEGETATIVE PHASE
(
SVP
) was up-regulated in
PnWB
-infected
C. roseus
plants, but most microRNA (
miRNA
) genes had repressed expression. Coincidentally, transgenic Arabidopsis (
Arabidopsis thaliana
) plants expressing the
PHYL1
gene of
PnWB
(
PHYL1
plants), which show leafy flower phenotypes, up-regulate
SVP
of Arabidopsis (
AtSVP
) but repress a putative regulatory
miRNA
of
AtSVP
, miR396. However, the mechanism by which PHYL1 regulates
AtSVP
and miR396 is unknown, and the evidence of miR396-mediated
AtSVP
degradation is lacking. Here, we show that miR396 triggers
AtSVP
messenger RNA (mRNA) decay using genetic approaches, a reporter assay, and high-throughput degradome profiles. Genetic evidence indicates that
PHYL1
plants and
atmir396a-1
mutants have higher
AtSVP
accumulation, whereas the transgenic plants overexpressing
MIR396
display lower
AtSVP
expression. The reporter assay indicated that target-site mutation results in decreasing the miR396-mediated repression efficiency. Moreover, degradome profiles revealed that miR396 triggers
AtSVP
mRNA decay rather than
miRNA
-mediated cleavage, implying that
AtSVP
caused miR396-mediated translation inhibition. We hypothesize that PHYL1 directly or indirectly interferes with miR396-mediated
AtSVP
mRNA decay and synergizes with other effects (e.g. MADS box transcription factor degradation), resulting in abnormal flower formation. We anticipate our findings to be a starting point for studying the posttranscriptional regulation of PHYL1 effectors in symptom development.
Human tissue samples are an invaluable and little available source of information for translational studies of congenital lung diseases such as Congenital Diaphragmatic Hernia (CDH) or Congenital ...Pulmonary Airway Malformation (CPAM).
We aimed to establish a human lung tissue biobank of CDH and CPAM patients together with age-matched controls, coupled with a clinical database.
Pathology records from autopsies or surgical specimens for CDH and CPAM cases between 1980 and 2017 were reviewed. For surviving individuals, clinical patient data was obtained from corresponding pediatric surgery reports. Formalin-fixed, paraffin-embedded tissues of patients and age-matched controls were systematically stored for further translational studies. RNA integrity was determined on selected CDH blocks.
A total of 16 CDH and 18 CPAM and age-matched control lung tissue blocks were included in our biobank. Ages ranged from 22 to 41 weeks of gestation (GA) in CDH (33.9 ± 6.35 weeks) and 26 weeks (GA) and 12 years in CPAM (2.3 ± 3.7 y). RNA isolation from CDH and control blocks yielded good RNA quality (OD 260/280 ratio: 2.01–2.09, OD 260/230 ratio: 2.04–2.09).
We established a unique human biobank for CDH and CPAM tissues. The combination with clinical patient data will allow us to design future translational studies to improve our understanding of the disease pathogenesis of these congenital malformations.
Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients ...with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.
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