CLaSSES: a New Digital Resource for Latin Epigraphy

CLaSSES (Corpus for Latin Sociolinguistic Studies on Epigraphic textS) is an annotated corpus aimed at (socio)linguistic research on Latin inscriptions. Provided with linguistic, extra- and meta-linguistic features, it can be used to perform quantitative and qualitative variationist analyses on Latin epigraphic texts. In particular, it allows the user to analyze spelling (and possibly phonetic-phonological) variants and to interpret them with reference to the dating, the provenance place, and the type of the texts. This paper presents the first macro-section of CLaSSES, focused on inscriptions of the archaic and early periods (CLaSSES I)

Rapid nontranscriptional effects of calcifediol and calcitriol

Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D(3), as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D(3) endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D(3), and it could lead to the identification of novel therapeutic targets able to modulate these actions

A breach in plant defences: Pseudomonas syringae pv. actinidiae targets ethylene signalling to overcome Actinidia chinensis pathogen responses

8openInternationalBothEthylene interacts with other plant hormones to modulate many aspects of plant metabolism, including defence and stomata regulation. Therefore, its manipulation may allow plant pathogens to overcome the host’s immune responses. This work investigates the role of ethylene as a virulence factor for Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit. The pandemic, highly virulent biovar of this pathogen produces ethylene, whereas the biovars isolated in Japan and Korea do not. Ethylene production is modulated in planta by light/dark cycle. Exogenous ethylene application stimulates bacterial virulence, and restricts or increases host colonisation if performed before or after inoculation, respectively. The deletion of a gene, unrelated to known bacterial biosynthetic pathways and putatively encoding for an oxidoreductase, abolishes ethylene production and reduces the pathogen growth rate in planta. Ethylene production by Psa may be a recently and independently evolved virulence trait in the arms race against the host. Plant- and pathogen-derived ethylene may concur in the activation/suppression of immune responses, in the chemotaxis toward a suitable entry point, or in the endophytic colonisationopenCellini, Antonio; Donati, Irene; Farneti, Brian; Khomenko, Iuliia; Buriani, Giampaolo; Biasioli, Franco; Cristescu, Simona M.; Spinelli, Francesco;Cellini, A.; Donati, I.; Farneti, B.; Khomenko, I.; Buriani, G.; Biasioli, F.; Cristescu, S.M.; Spinelli, F

68Ga-PSMA-11 PET/MR Can Be False Positive in Normal Prostatic Tissue

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the cytosol of normal prostate tissue and highly overexpressed on the membrane of prostate cancer, therefore increasingly used to image prostate cancer. We report a case of a 65-year-old man with two focal PSMA-positive areas on a Ga-PSMA-11 PET/MR, one corresponding to a prostate carcinoma (Gleason score 4 + 3) and another region without any evidence of malignancy, but with corresponding high PSMA-expression on immunohistochemistry

Prediction of pelvic lymph node metastases and PSMA PET positive pelvic lymph nodes with multiparametric MRI and clinical information in primary staging of prostate cancer

PURPOSE To compare the accuracy of multiparametric MRI (mpMRI), $^{68}$Ga-PSMA PET and the Briganti 2019 nomogram in the prediction of metastatic pelvic lymph nodes (PLN) in prostate cancer, to assess the accuracy of mpMRI and the Briganti nomogram in prediction of PET positive PLN and to investigate the added value of quantitative mpMRI parameters to the Briganti nomogram. METHOD This retrospective IRB-approved study included 41 patients with prostate cancer undergoing mpMRI and $^{68}$Ga-PSMA PET/CT or MR prior to prostatectomy and pelvic lymph node dissection. A board-certified radiologist assessed the index lesion on diffusion-weighted (Apparent Diffusion Coefficient, ADC; mean/volume), T2-weighted (capsular contact length, lesion volume/maximal diameters) and contrast-enhanced (iAUC, k$_{ep}$, K$^{trans}$, v$_{e}$) sequences. The probability for metastatic pelvic lymph nodes was calculated using the Briganti 2019 nomogram. PET examinations were evaluated by two board-certified nuclear medicine physicians. RESULTS The Briganti 2019 nomogram performed superiorly (AUC: 0.89) compared to quantitative mpMRI parameters (AUCs: 0.47-0.73) and $^{68}$Ga-PSMA-11 PET (AUC: 0.82) in the prediction of PLN metastases and superiorly (AUC: 0.77) in the prediction of PSMA PET positive PLN compared to MRI parameters (AUCs: 0.49-0.73). The addition of mean ADC and ADC volume from mpMRI improved the Briganti model by a fraction of new information of 0.21. CONCLUSIONS The Briganti 2019 nomogram performed superiorly in the prediction of metastatic and PSMA PET positive PLN, but the addition of parameters from mpMRI can further improve its accuracy. The combined model could be used to stratify patients requiring ePLND or PSMA PET

N-Acyl Homoserine Lactones and Lux Solos Regulate Social Behaviour and Virulence of Pseudomonas syringae pv. actinidiae

The phyllosphere is a complex environment where microbes communicate through signalling molecules in a system, generally known as quorum sensing (QS). One of the most common QS systems in Gram-negative proteobacteria is based on the production of N-acyl homoserine lactones (AHLs) by a LuxI synthase and their perception by a LuxR sensor. Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit, colonises plant phyllosphere before penetrating via wounds and natural openings. Since Psa genome encodes three LuxR solos without a cognate LuxI, this bacterium may perceive diffusible signals, but it cannot produce AHLs, displaying a non-canonical QS system. The elucidation of the mechanisms underlying the perception of environmental cues in the phyllosphere by this pathogen and their influence on the onset of pathogenesis are of crucial importance for a long-lasting and sustainable management of the bacterial canker of kiwifruit. Here, we report the ability of Psa to sense its own population density and the presence of surrounding bacteria. Moreover, we show that Psa can perceive AHLs, indicating that AHL-producing neighbouring bacteria may regulate Psa virulence in the host. Our results suggest that the ecological environment is important in determining Psa fitness and pathogenic potential. This opens new perspectives in the use of more advanced biochemical and microbiological tools for the control of bacterial canker of kiwifruit

Time evolution of restless legs syndrome in haemodialysis patients

Abstract Background Restless legs syndrome (RLS) is characterized by an urge to move the extremities, accompanied by paraesthesiae, in the evening and at night. Uraemic RLS, a type of secondary RLS, occurs commonly in chronic kidney disease and end-stage renal disease. Progression of uraemic RLS over time is unclear. Therefore we investigated the prevalence, progression over time, risk factors and impact on survival of uraemic RLS in a cohort of dialysis patients. Methods We reviewed at the 7-year follow-up a cohort of haemodialysis (HD) patients we had previously investigated for RLS, through interviews, validated questionnaires and analysis of demographic and clinical data. Results At the 7-year follow-up, RLS was present in 16% of patients, with a persistence rate of 33%. A correlation was obtained between RLS and older age, diabetes, low albumin and low body mass index. RLS was associated with reduced overall survival (median survival of 3.3 versus 3.7 years), particularly with the continuous form of RLS (1.61 years). There was a higher incidence of myocardial infarction and peripheral vascular disease, although not reaching statistical significance. RLS patients had absolute higher scores in all quality of life domains. A large majority of study patients (96%) reported being symptom-free within a few days or weeks following kidney transplantation. Conclusions The development of RLS, especially the continuous form, in patients undergoing HD has important consequences associated with decreased survival. Our results indicated an association between uraemic RLS and ageing, diabetes and malnutrition. Considerable efforts should be focused on the treatment of RLS, since it significantly and persistently impacts the quality of life of HD patients. Kidney transplantation could represent an effective treatment option for that RLS impacts on dialysis patients' quality of life, thus confirming the secondary nature of RLS in most HD patients

Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response?

BACKGROUND: Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. The role of adjuvant chemotherapy is debated. New prognostic and predictive factors are needed. METHODS: We reviewed patients with localized SS; SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry. RESULTS: Tumor samples from 88 SS patients (45 female; 43 male) with median age 37 years (range 11-63) were selected. The size of the lesion was\u2009>\u20095 cm in 68% of patients and 34% of cases presented biphasic histotype. All patients underwent surgery, 56% adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF-1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60-81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear expression, and 73% (95% CI 61-85%; P\u2009=\u20090.05) in negative patients. 5-year OS was 47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86% (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found according to Ezrin expression. By multivariate analysis, nuclear expression of CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS patient survival linked to the use of chemotherapy. CONCLUSIONS: Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS. We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments

Comparative transcriptome analysis of the interaction between Actinidia chinensis var. chinensis and Pseudomonas syringae pv. Actinidiae in absence and presence of acibenzolar-S-methyl

Background: Since 2007, bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has become a pandemic disease leading to important economic losses in every country where kiwifruit is widely cultivated. Options for controlling this disease are very limited and rely primarily on the use of bactericidal compounds, such as copper, and resistance inducers. Among the latter, the most widely studied is acibenzolar-S-methyl. To elucidate the early molecular reaction of kiwifruit plants (Actinidia chinensis var. chinensis) to Psa infection and acibenzolar-S-methyl treatment, a RNA seq analysis was performed at different phases of the infection process, from the epiphytic phase to the endophytic invasion on acibenzolar-S-methyl treated and on non-treated plants. The infection process was monitored in vivo by confocal laser scanning microscopy. Results: De novo assembly of kiwifruit transcriptome revealed a total of 39,607 transcripts, of which 3360 were differentially expressed during the infection process, primarily 3 h post inoculation. The study revealed the coordinated changes of important gene functional categories such as signaling, hormonal balance and transcriptional regulation. Among the transcription factor families, AP2/ERF, MYB, Myc, bHLH, GATA, NAC, WRKY and GRAS were found differentially expressed in response to Psa infection and acibenzolar-S-methyl treatment. Finally, in plants treated with acibenzolar-S-methyl, a number of gene functions related to plant resistance, such as PR proteins, were modulated, suggesting the set-up of a more effective defense response against the pathogen. Weighted-gene coexpression network analysis confirmed these results. Conclusions: Our work provides an in-depth description of the plant molecular reactions to Psa, it highlights the metabolic pathway related to acibenzolar-S-methyl-induced resistance and it contributes to the development of effective control strategies in open field

Red and Blue Light Differently Influence Actinidia chinensis Performance and Its Interaction with Pseudomonas syringae pv. Actinidiae

Light composition modulates plant growth and defenses, thus influencing plant–pathogen interactions. We investigated the effects of different light-emitting diode (LED) red (R) (665 nm) and blue (B) (470 nm) light combinations on Actinidia chinensis performance by evaluating biometric parameters, chlorophyll a fluorescence, gas exchange and photosynthesis-related gene expression. Moreover, the influence of light on the infection by Pseudomonas syringae pv. actinidiae (Psa), the etiological agent of bacterial canker of kiwifruit, was investigated. Our study shows that 50%R–50%B (50R) and 25%R–75%B (25R) lead to the highest PSII efficiency and photosynthetic rate, but are the least effective in controlling the endophytic colonization of the host by Psa. Monochromatic red light severely reduced ΦPSII, ETR, Pn, TSS and photosynthesis-related genes expression, and both monochromatic lights lead to a reduction of DW and pigments content. Monochromatic blue light was the only treatment significantly reducing disease symptoms but did not reduce bacterial endophytic population. Our results suggest that monochromatic blue light reduces infection primarily by modulating Psa virulence more than host plant defenses