CIUHCT

"Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder among Caucasians, is caused by mutations in the gene that encodes for the Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR). With more than 1600 mutations
reported, a single mutation– the deletion of phenylalanine residue at position 508 – accounts for more than 70% of chromosomes worldwide. The presence of this mutation causes CFTR retention at the endoplasmic reticulum (ER) and its early degradation at the proteasome.
We have studied the effect of AMPK phosphorylation on a CFTR
variant (S573C) found in non-CF patients with pancreatitis. This variant was found to be less functional than wt-CFTR and more sensitive to AMPK phosphorylation. Our results suggest that S573 plays an important role in channel gating.
We have also studied the effect of CK2 phosphorylation upon
CFTR function and found that TBB inhibits wt-CFTR currents without affecting F508del-CFTR. Further insight was achieved by mutating three putative CK2-phosphorylation sites. (S422, S511 and T1471). Mutating S511 (A or D) did not have any detectable effect upon wt-CFTR function, while mutating S422 (A or D) significantly , decreases or increases CFTR function, respectively. Both T1471A- and T1471DCFTR are less functional than wt-CFTR, and significantly inhibitable by TBB, similarly to S422 mutants. These data suggest that CK2 may be a positive effector for CFTR biogenesis, trafficking or function.
Mutating Y512, the SYK consensus phosphorylation site, into an A results in a significant increase in CFTR function in both wt- and F508del backgrounds. This mutation may cause a conformational change that favours channel gating.
Altogether, these data provide novel insight into CFTR regulation
by phosphorylation and thus to our understanding of the molecular mechanisms that govern its trafficking and/or function.


Key words: CFTR, Cystic Fibrosis, Phosphorylation, CK2, SYK,
AMPK, Metformin"

The Society of Jesus was one of the most important institution involved in the teaching and practice of mathematics and astronomy in the 16th, 17th and 18th centuries in Europe and East Asia.In Portugal,from 1540 to 1759,the Jesuits developed and maintained a vast network of colleges and were responsible for the education of around 20000 pre-university students. With the expulsion of the Orderby the Marquis de Pombal,in 1759,the Jesuit colleges were closed and the educational system was dismantled.The secularization of the educational system was accompanied by a massive political campaign in which the Jesuits were considered the major obstacle to scientific progress.This accusation of obscurantism and scientific illiteracy was largely accepted in Portugal in the 18th century and persisted throughout the 19th century.When the Jesuits returned to Portugal,in the 1850s,in order to recover their scientific and social credibility,they made scientific education and research a priority.Among their initiatives,they founded the colleges of Campolide (Lisboa,1858) and São Fiel (Louriçal do Campo,1863),two of the most important secondary schools in Portugal that made relevant efforts in the teaching of science,and established Brotéria,a scientific journal with original research papers.Considered one of,the most significant learned journals printed in Portugalin the 20th century,it published 400 popularization articles and more than 1300 research papers on zoology,botany,biochemistry and molecular genetics.By analyzing the scientific and pedagogical activities of the Portuguese Jesuits in the 19th and 20th century,I expect to shed some light into the outer tensions and the inner desires that led a religious order to deeply engage in scientific practices in order to recover its social and scientific credibility.

A acusação de que os jesuítas teriam sido os principais responsáveis pelo “geral idiotismo” em Portugal alcançou uma longevidade, uma transversalidade e uma influência absolutamente invulgares na nossa história. Apesar de remontar a meados do século XVIII, a tese de obscurantismo pombalina influenciou não só a restauração da Companhia de Jesus, mas também a definição das suas prioridades educativas e das suas estratégias apostólicas ao longo dos séculos XIX e XX. Dada a centralidade do obscurantismo científico na argumentação utilizada por Pombal, os jesuítas procuraram, em primeiro lugar, rebater as críticas relacionadas com a educação e com a prática das ciências e, por isso, promoveram o ensino experimental das ciências naturais nos seus colégios e fundaram uma revista científica que acabaria por se revelar central para o desenvolvimento no nosso país de áreas científicas como a botânica, a zoologia, a bioquímica e a genética molecular.

This monograph is based on my doctoral dissertation on Jesuit science and education in nineteenth and twentieth-century Portugal. In 2015 it was awarded an honorable mention in Portuguese contemporary history: Menção Honrosa do Prémio Victor de Sá de História Contemporânea.

Carlos Zimmermann SJ was an important pedagogue and one of the most influential naturalists working in Portugal at the beginning of the twentieth century. He was an active promoter of an experimental approach to the teaching of the natural sciences, and one of the founders of the leading Portuguese scientific journal, Brotéria. His main area of research was the identification and classification of novel species of diatoms (one of the largest groups of microscopic algae). In the aftermath of the expulsion of the religious orders in 1910, the newly-established Portuguese Republic confiscated Jesuit scientific books, instruments and collections, including those produced by Zimmermann. Exiled to Brazil from 1911, he remained there until his death in 1950. This article focuses on the main questions relating to the organisation, apprehension, and partial restitution of these collections. By analysing a set of sixteen unpublished documents, recently found in a private archive and now published as an appendix, the article reconstructs the trajectory and significance of Zimmermann’s  body of work. It elucidates, furthermore, the complex diplomatic and political circumstances, as well as the central role of  correspondence networks, that led to the retrieval of these  documents.