The circadian clock, metabolism and obesity

In the last decades, obesity has been on the rise becoming a burden for health care systems. The reasons behind this rise are most likely caused by lifestyle rather than by an increase in gene mutations, because manifestations of genetic alterations would take longer than just a few decades. Lifestyle has a great impact on the circadian system and therefore on the body internal organization of physiological and biochemical processes, regulating various aspects of behavior and metabolism. In the following, I will discuss recent studies delineating relationships between metabolic processes and the circadian system, how metabolites and nutrients regulate the circadian clock and how nuclear receptors can act as metabolic sensors and clock regulators. Finally, I will discuss how clock modulation and feeding patterns influence the development of obesity

PSD3 downregulation confers protection against fatty liver disease

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD. Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.Peer reviewe

Roadmap on biology in time varying environments

Biological organisms experience constantly changing environments, from sudden changes in physiology brought about by feeding, to the regular rising and setting of the Sun, to ecological changes over evolutionary timescales. Living organisms have evolved to thrive in this changing world but the general principles by which organisms shape and are shaped by time varying environments remain elusive. Our understanding is particularly poor in the intermediate regime with no separation of timescales, where the environment changes on the same timescale as the physiological or evolutionary response. Experiments to systematically characterize the response to dynamic environments are challenging since such environments are inherently high dimensional. This roadmap deals with the unique role played by time varying environments in biological phenomena across scales, from physiology to evolution, seeking to emphasize the commonalities and the challenges faced in this emerging area of research

The Seventeenth-Century Vida of the Proselyte Abraham Pelengrino, alias Manoel Cardoso de Macedo: Analysis and Translation

The 1668-9 Cópia da vida de bemaventurado, claiming to be a copy of text written by Manoel Cardoso de Macedo who later adopted the name Abraham Pelengrino (d. 1652), is a unique testimony of an early modern conversion to Judaism, a phenomenon of which few descriptions have survived. The English translation of the Portuguese original presented in this article shows, among others, how such conversions were deeply personal experiences while at the same time served converts’ apologetic needs and, possibly, the Jewish community’s anti-Christian polemics. The essay that introduces the translation addresses questions of authorship, genre, and, focusing on discrepancies between facts described in the text and other sources, explores the Vida as a literary construct.publishedVersio

Inquisitorial Prison as a site of Cross-Cultural Encounter: the Case of Manuel Cardoso de Macedo aka Abraham Pelengrino Guer

Prisons are often a site of cross-cultural encounter and religious illumination. People from different ethnic and socio-economic backgrounds meet each other and inevitably share ideas and experiences. The inquisitorial prison housed individuals who were accused of crimes of conscience and thus the encounters that a prisoner would have in a secret prison of the Inquisition would often enough center on issues of belief and identity. I will look at a case from Lisbon in the early 1600s, where individuals from different socio-economic, ethnic and religious backgrounds meet and transform each other\u27s religious outlook and commitments within prison walls. I will pay attention to other, non-incarceratory places of meeting as a way of appreciating the continuities and disruptions between life inside and outside of the prison space. Manuel Cardoso de Macedo (1585–1652) was an Azorean Old Christian who found his way to Judaism after first embracing Calvinsim as a teenager living in London and then discovering “the Law of Moses” in a cell he shared with an accused Judaizer in the prison of the Lisbon Holy Office. Cardoso eventually escapes Portugal along with members of a large converso family that he met in prison and he converts to Judaism in Hamburg taking the Hebrew name of Abraham Pelengrino Guer. He settles in Amsterdam where he lives within the Portuguese community until his death in 1653. Cardoso’s religious odyssey begins in England. His father was in the dye and textile trade and conducted extensive business with England. He sent his teenage son, Manuel to England in 1599 to master the language and apprentice with some business associates presumably in preparation for a life in the family business. While in England he encountered the Bible in English translation. This, according to his telling in the Vida changed his life, setting off a series of independently inspired religious inquiries. He writes: “Scripture was the first thing that they placed in my hand after the ABC.” He soon became enthralled with Protestant ideas, eventually rejecting “the religion of his parents” for Calvinism. On trips back to the Azores to visit his family he managed to keep his heresy a secret, but eventually word got out and he was arrested while visiting São Miguel and was eventually sent to the Lisbon Holy Office in 1608. It is in prison where he rejects Calvinism after his discovery of Judaism. Cardoso eventually was released from prison and after connecting with a group of Portuguese conversos he knew from his time in prison, he escaped Lisbon for Hamburg where he formally converted, eventually settling in Amsterdam. Around the 1620s he composed his spiritual autobiography La Vida del buenaventurado Abraham Pelengrino Guer. The encounters with ethnic and religious others within the warped “third space” of the inquisitorial prison allow for much more than an exchange of new ideas or the forging of new friendships. These encounters allow for religious transformations and a radical shift in the subjects’ sense of self. The following texts include scenes where space informs the development of Cardoso’s self presentation as developed in his autobiography. I have selected examples from both within his Inquisitorial experience and outside of it. I look forward to the discussion of what the spatial elements of these scenes of encounter and self reflection add to our understanding of this early modern life