Festivals, fools and the Fasti: the Quirinalia and the Feriae Stultorum (Ovid, Fast. 2.475-532)

Introduction: Ovid’s Fasti presents many challenges to the reader: its subject matter, the festivals and anniversaries of the Roman year, is less immediately accessible than much of Ovid’s poetry; and unlike his earlier works, where familiarity with the literary context provides plenty of material for literary criticism, the Fasti is in constant dialogue not just with literature but also with the fabric of Rome – its myths and monuments, its rituals and politics. As such, the Fasti more than many texts requires an awareness of its social, historical and religious context to be fully appreciated

Rescue of Synthetic Genomic RNA Analogs of Rabies Virus by Plasmid-Encoded Proteins

Proteins eolirely expressed from cDNA wen used to rescue synthetic RNA genome analogs into infectious defective particles or rabies virus (RV). Synthetic negative-stranded RNAs coßtalning 3' · and S'-terminal RV sequences and tnlßscriptional signal sequences wen transcribed (rom plasmids transfeded into cells expressing 1'7 RNA polymerase (rom recombinant vaccinia virus. After simultaneous expression or RV N, P, and L proteiDS (rom plasmids containing a T7 RNA polymerase promoter, tbe synthetic genomes wen encapsidated. replicated, and transcribed by tbe RV polymerase proteiDS. Insertion or the bac1erial chloramphenicol acetyUransferase gene or l3·galactosidase (IacZ) gene between the 3 ' and 5 ' termini containing transcriptional signal sequenees resulted in transcription of mRNAs and expression of ehloramphenlco

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Targeting ROCK activity to disrupt and prime pancreatic cancer for chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease; the identification of novel targets and development of effective treatment strategies are urgently needed to improve patient outcomes. Remodeling of the pancreatic stroma occurs during PDAC development, which drives disease progression and impairs responses to therapy. The actomyosin regulatory ROCK1 and ROCK2 kinases govern cell motility and contractility, and have been suggested to be potential targets for cancer therapy, particularly to reduce the metastatic spread of tumor cells. However, ROCK inhibitors are not currently used for cancer patient treatment, largely due to the overwhelming challenge faced in the development of anti-metastatic drugs, and a lack of clarity as to the cancer types most likely to benefit from ROCK inhibitor therapy. In 2 recent publications, we discovered that ROCK1 and ROCK2 expression were increased in PDAC, and that increased ROCK activity was associated with reduced survival and PDAC progression by enabling extracellular matrix (ECM) remodeling and invasive growth of pancreatic cancer cells. We also used intravital imaging to optimize ROCK inhibition using the pharmacological ROCK inhibitor fasudil (HA-1077), and demonstrated that short-term ROCK targeting, or ‘priming’, improved chemotherapy efficacy, disrupted cancer cell collective movement, and impaired metastasis. This body of work strongly indicates that the use of ROCK inhibitors in pancreatic cancer therapy as ‘priming’ agents warrants further consideration, and provides insights as to how transient mechanical manipulation, or fine-tuning the ECM, rather than chronic stromal ablation might be beneficial for improving chemotherapeutic efficacy in the treatment of this deadly disease

La Difusió tecnocientífica al Col·legi d'Enginyers Tècnics Industrials de Manresa (1955-2005)

Manresa, centre of an important industrial district, has counted with an Association of Technical Engineers during the second half of the XXth century. The institution has developed an important formative activity that can be divided into courses and into visits to technologically innovative facilities. Courses have been dealt with the organization of production and of work and on other aspects of interest for the technicians as technical and scientific novelties. The subject of courses is an indicator of the rhythm of the transmission of technological novelties in Spain. Moreover, the Association has collaborated in the improvement of technical education of all levels in its region

Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells

BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first-line setting