9 research outputs found
Canine Filamentous Dermatitis Associated with Borrelia Infection
Background: Although canine clinical manifestations of Lyme disease vary widely, cutaneous manifestations are not well documented in dogs. In contrast, a variety of cutaneous manifestations are reported in human Lyme disease caused by the spirochete Borrelia burgdorferi. A recently recognized dermopathy associated with tickborne illness known as Morgellons disease is characterized by brightly-colored filamentous inclusions and projections detected in ulcerative lesions and under unbroken skin. Recent studies have demonstrated that the dermal filaments are collagen and keratin biofibers produced by epithelial cells in response to spirochetal infection. We now describe a similar filamentous dermatitis in canine Lyme disease. Methods and Results: Nine dogs were found to have cutaneous ulcerative lesions containing embedded or projecting dermal filaments. Spirochetes characterized as Borrelia spp. were detected in skin tissue by culture, histology, immunohistochemistry, polymerase chain reaction (PCR) and gene sequencing performed at five independent laboratories. Borrelia DNA was detected either directly from skin specimens or from cultures inoculated with skin specimens taken from the nine canine study subjects. Amplicon sequences from two canine samples matched gene sequences for Borrelia burgdorferi sensu stricto. PCR amplification failed to detect spirochetes in dermatological specimens from four healthy asymptomatic dogs. Conclusions: Our study provides evidence that a filamentous dermatitis analogous to Morgellons disease may be a manifestation of Lyme disease in domestic dogs
Overlapping ATP2C1 and ASTE1 genes in human genome: Implications for SPCA1 expression
Abstract: The ATP2C1 gene encodes for the secretory pathway calcium (Ca 2+)-ATPase pump (SPCA1), which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic organization between mouse and human we speculate that the overlap between ATP2C1 and ASTE1 genes only in humans could explain this different response to ATP2C1 dysregulation. We propose that ASTE1, overlapping with ATP2C1 in humans, affects alternative splicing, and potentially protein expression of the latter. If dysregulated, the composition of the SPCA1 isoform pool could diverge from the physiological status, affecting cytosolic Ca 2+-signaling, and in turn perturbing cell division, leading to cell death or to neoplastic transformation
The 3′ UTR of the human CTLA4 mRNA can regulate mRNA stability and translational efficiency
T cell activation results from the integration of signals generated through the T cell antigen receptor–CD3 complex with those from additional positive and negative regulatory pathways mainly mediated by the engagement of costimulatory receptors on T cells. Disruption of this balance leads to a defective immune response or alternative over-activation of the immune system. CTLA-4 plays a critical role in downregulating T cell responses. Autoimmune diseases have shown genetic linkage to the CTLA4 locus. In this report we demonstrate that the 3′ UTR of CTLA4 regulates firefly luciferase reporter gene expression, can confer instability to CTLA4 mRNA and can influence its translation efficiency in vitro
Improved definition of the mouse transcriptome via targeted RNA sequencing
Targeted RNA sequencing (CaptureSeq) uses oligonucleotide probes to capture RNAs for sequencing, providing enriched read coverage, accurate measurement of gene expression, and quantitative expression data. We applied CaptureSeq to refine transcript annotations in the current murine GRCm38 assembly. More than 23,000 regions corresponding to putative or annotated long noncoding RNAs (lncRNAs) and 154,281 known splicing junction sites were selected for targeted sequencing across five mouse tissues and three brain subregions. The results illustrate that the mouse transcriptome is considerably more complex than previously thought. We assemble more complete transcript isoforms than GENCODE, expand transcript boundaries, and connect interspersed islands of mapped reads. We describe a novel filtering pipeline that identifies previously unannotated but high-quality transcript isoforms. In this set, 911 GENCODE neighboring genes are condensed into 400 expanded gene models. Additionally, 594 GENCODE lncRNAs acquire an open reading frame (ORF) when their structure is extended with CaptureSeq. Finally, we validate our observations using current FANTOM and Mouse ENCODE resources.The authors acknowledge the following funding sources: an Australian National Health and Medical Research Council (NHMRC) Australia Fellowship (631668 to J.S.M. and 631542 to M.E.D.); an NHMRC Early Career Fellowship (APP1072662 to M.B.C.); an EMBO Long Term Fellowship (ALTF 864-2013 to M.B.C.); an Australian National Health and Medical Research Council (NHMRC) Project Grant (APP1062106 to T.R.M.) and Career Development Fellowship (APP1062470 to T.R.M); and an EMBL Interdisciplinary Postdoc (EIPOD) under Marie Curie Actions (COFUND) (to G.B.)
Improved definition of the mouse transcriptome via targeted RNA sequencing
Targeted RNA sequencing (CaptureSeq) uses oligonucleotide probes to capture RNAs for sequencing, providing enriched read coverage, accurate measurement of gene expression, and quantitative expression data. We applied CaptureSeq to refine transcript annotations in the current murine GRCm38 assembly. More than 23,000 regions corresponding to putative or annotated long noncoding RNAs (lncRNAs) and 154,281 known splicing junction sites were selected for targeted sequencing across five mouse tissues and three brain subregions. The results illustrate that the mouse transcriptome is considerably more complex than previously thought. We assemble more complete transcript isoforms than GENCODE, expand transcript boundaries, and connect interspersed islands of mapped reads. We describe a novel filtering pipeline that identifies previously unannotated but high-quality transcript isoforms. In this set, 911 GENCODE neighboring genes are condensed into 400 expanded gene models. Additionally, 594 GENCODE lncRNAs acquire an open reading frame (ORF) when their structure is extended with CaptureSeq. Finally, we validate our observations using current FANTOM and Mouse ENCODE resources.The authors acknowledge the following funding sources: an Australian National Health and Medical Research Council (NHMRC) Australia Fellowship (631668 to J.S.M. and 631542 to M.E.D.); an NHMRC Early Career Fellowship (APP1072662 to M.B.C.); an EMBO Long Term Fellowship (ALTF 864-2013 to M.B.C.); an Australian National Health and Medical Research Council (NHMRC) Project Grant (APP1062106 to T.R.M.) and Career Development Fellowship (APP1062470 to T.R.M); and an EMBL Interdisciplinary Postdoc (EIPOD) under Marie Curie Actions (COFUND) (to G.B.)
Intraoperative Predictors and Proposal for a Novel Prognostic Risk Score for In-Hospital Mortality after Open Repair of Ruptured Abdominal Aortic Aneurysms (SPARTAN Score)
(1) Background: Several mortality risk scores have been developed to predict mortality in ruptured abdominal aortic aneurysms (rAAAs), but none focused on intraoperative factors. The aim of this study is to identify intraoperative variables affecting in-hospital mortality after open repair and develop a novel prognostic risk score. (2) Methods: The analysis of a retrospectively maintained dataset identified patients who underwent open repair for rAAA from January 2007 to October 2023 in three Italian tertiary referral centers. Multinomial logistic regression was used to calculate the association between intraoperative variables and perioperative mortality. Independent intraoperative factors were used to create a prognostic score. (3) Results: In total, 316 patients with a mean age of 77.3 (SD ± 8.5) were included. In-hospital mortality rate was 30.7%. Hemoperitoneum (p p = 0.001), and operation times of >240 min (p = 0.008) were negative predictors of perioperative mortality, while the patency of at least one hypogastric artery had a protective role (p = 0.008). Numerical values were assigned to each variable based on the respective odds ratio to create a risk stratification for in-hospital mortality. (4) Conclusions: rAAA represents a major cause of mortality. Intraoperative variables are essential to estimate patients’ risk in surgically treated patients. A prognostic risk score based on these factors alone may be useful to predict in-hospital mortality after open repair
Il progetto Primarte
Il progetto PRIMARTE, acronimo di "apProccio integrato di Rete per l'Innovazione nelle Metodologie di diAgnostica e inteRvento sul paTrimonio artistico e architEttonico", è un progetto di ricerca e sviluppo nel campo della diagnostica, conservazione e valorizzazione dei beni culturali, finanziato all'interno del Bando Unico 2012- regione Toscana-POR CREO 2007-2013. E' un progetto multidisciplinare, condotto da un partenariato composto da Organismi di Ricerca e Piccole Medie Imprese che coinvolge professionalità qualificate con competenze diverse ma complementari nella ricerca scientifica e umanistica. Ha lo scopo di mettere a punto, intorno ad un 'cantiere pilota', una metodologia integrata per la diagnostica sui beni culturali, mediata da strumenti multimediali che siano facilmente fruibili ed esportabili su scala internazionale