Putting the Indices into practice: censoring science in early modern Portugal.

During the sixteenth and seventeenth centuries, the Inquisition was the institution most invested in the censorship of printed books in the Portuguese empire. Besides publishing the Indices of Forbidden Books, the Holy Office was also responsible for overseeing their implementation and ensuring their efficacy in preventing the importation, reading, and circulation of banned books. Overall, the sixteenth-century Indices condemned 785 authors and 1081 titles, including 52 authors and 85 titles of medicine, natural history, natural philosophy, astronomy, chronology, cosmography, astrology, and divinatory arts. By looking at the largest collection of early modern scientific books in Portugal, I will argue that a closer inspection of marginalia and ownership, and the establishment of a typology of expurgations is essential for the comprehension of the actual practices and the mechanisms of censorship. By examining the material evidence of censorship, in order to reconstruct expurgation practices, this paper reveals the processes and effectiveness of ecclesiastical control in the Portuguese Inquisition and highlights the differences between what inquisitors wrote in the Indices and what others put into practice.

For the greater credibility: Jesuit science and education in modern Portugal (1858-1910).

Upon the restoration of the Society of Jesus in Portugal in 1858, the Jesuits founded two important colleges that made significant efforts in the promotion of hands-on experimental teaching of the natural sciences. At the Colégio de Campolide (Lisbon, 1858-1910) and the Colégio de São Fiel (Louriçal do Campo, 1863-1910) the Jesuits created modern chemistry and physics laboratories, organized significant botanical, zoological and geological collections, promoted scientific expeditions with their students to observe eclipses and to collect novel species of animals and plants, and engaged in original research work in physics, botany, and zoology. The successful implementation of modern scientific practices gained these colleges public recognition as the most prominent secondary institutions in nineteenth-century Portugal, and this made a major contribution to countering the widespread and commonly accepted anti-Jesuit accusations of obscurantism and scientific backwardness.

Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.

Previously, the pleiotropic "master kinase" casein kinase 2 (CK2) was shown to interact with CFTR, the protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. CFTR possesses two CK2 phosphorylation sites (S422 and T1471), with unclear impact on its processing and trafficking. Here, we investigated the effects of mutating these CK2 sites on CFTR abundance, maturation, and degradation coupled to effects on ion channel activity and surface expression. We report that CK2 inhibition significantly decreased processing of wild-type (wt) CFTR, with no effect on F508del CFTR. Eliminating phosphorylation at S422 and T1471 revealed antagonistic roles in CFTR trafficking: S422 activation versus T1471 inhibition, as evidenced by a severe trafficking defect for the T1471D mutant. Notably, mutation of Y512, a consensus sequence for the spleen tyrosine kinase (SYK) possibly acting in a CK2 context adjacent to the common CF-causing defect F508del, had a strong effect on both maturation and CFTR currents, allowing the identification of this kinase as a novel regulator of CFTR. These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation.

Metformin treatment of diabetes mellitus increases the risk for pancreatitis in patients bearing the CFTR-mutation S573C.

Metformin use in diabetes can cause acidosis and might be linked to pancreatitis. Here, we mechanistically focus on this relationship via a point mutation in the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7). CFTR is an ATP-hydrolyzing, cAMP/PKA-activated anion channel regulating pancreatic bicarbonate/chloride secretion across duct-facing apical membranes in epithelia. CFTR has two nucleotide binding domains (NBD1/2) which clamp two ATP molecules across their opposed, inverted interfacial surfaces which generates anion-conductance after ATP hydrolysis. Notably, CFTR mutations not causal for classical cystic fibrosis segregate with unexplained pancreatitis and one of these lies in NBD1 near its ATP-clamp (S573C; close to the Walker B aspartate D572). We recently showed that after raising [cAMP], wt-CFTR chloride-conductance, when expressed in Xenopus oocytes, remains elevated despite the presence of metformin. Yet here, we find that S573C-CFTR manifests a metformin-inhibitable whole cell chloride-conductance after cAMP elevation. In the absence of metformin, cAMP-activated S573C-CFTR also displays a reduced anion-conductance relative to wt-CFTR. Furthermore, intra-oocyte acidification inhibited wt-CFTR and abolished S573C-CFTR conductance. We conclude that defective S573C-CFTR remains both poorly conducting and inhibited by metformin and intracellular acidosis. This might explain the propensity to pancreatitis with this rare CF mutation.