Dusza, ciało i tabu : studia nad sakralnością praindoeuropejskiego formantu *u w łacińskiej terminologii anatomicznej

The author of the monograph Soul, Body and the Taboo investigates the hypotheses of two German scholars of the first half of the 20th century: Franz Specht and Wilhelm Havers, according to whom, one of the Pre-Indo-European formatives—the formative *u—was at its roots deeply connected with the sacred and the supernatural. For that reason, the formative was included in the words denoting objects of sacred, dangerous, supernatural or taboo nature. In her search of the echoes of the formative *u, the author focuses predominantly on the analysis of those body parts which, according to the English philologists James G. Frazer and Richard B. Onians, were supposed to be regarded by the Pre-Indo-Europeans as the vessels of the soul, the main object of the taboo. Apart from that, the author analyses the names of organs which played vital parts in the practices of the haruspices, as well as those body parts which could arouse fear due to either the virulent forces residing within them or magical and apotropaic character. The etymological study focuses first and foremost on Latin nomenclature. However, the author refers also to Pre-Indo-European nomenclature and the current state of other Indo-European languages. The etymological analysis is further strengthened through the cultural study of the beliefs and superstitions of ancient Romans, which they might have inherited from their ancestors

THE COLOURS IN THE PRIMITIVE HISPANO-ROMANCE FROM THE PROTO-INDO-EUROPEAN TO THE ORIGINS OF THE SPANISH LANGUAGE

The article presents the names of colours in the primitive Hispano-Romance, the language of Christians in the Iberian Peninsula in the early Middle Ages. This language is known from notarial acts whose vocabulary was collected in the glossary Léxico hispánico primtivo. The author analyses the colour names included in it against Latin and Indo-European backgrounds. Etymologically, the core of this part of the Ibero-Romance corpus has Latin origins. The influence of the Arabic and Visigoth language resulted less than could be expected

Rozwój leksemów oznaczających wujka/ciotkę, kuzynów, szwagra/ szwagierkę w hispano-romańskim i polskim w perspektywie porównawczej

The aim of the article is to compare the development of some family-related vocabulary from Latin (with PIE backgrounds) to Hispano-Romance with the old and modern Polish terms. The comparative analysis covers the words for ‘uncle’/’aunt’, ‘brother/sister-in-law’ and ‘cousins’. The author tries to explain lexical changes with reference to social changes that took place over the centuries.Celem artykułu jest porównanie rozwoju słownictwa związanego z rodziną w języku polskim i hispano-romańskim na tle łacińskim. Analiza porównawcza dotyczy nazw wujka/ciotki, szwagra/szwagierki i kuzynów. Autorka próbuje wytłumaczyć zmiany leksykalne zmianami społecznymi, które miały miejsce na przełomie wieków

Genome-wide CRISPR-KO Screen Uncovers mTORC1-Mediated Gsk3 Regulation in Naive Pluripotency Maintenance and Dissolution

Summary: The genetic basis of naive pluripotency maintenance and loss is a central question in embryonic stem cell biology. Here, we deploy CRISPR-knockout-based screens in mouse embryonic stem cells to interrogate this question through a genome-wide, non-biased approach using the Rex1GFP reporter as a phenotypic readout. This highly sensitive and efficient method identified genes in diverse biological processes and pathways. We uncovered a key role for negative regulators of mTORC1 in maintenance and exit from naive pluripotency and provided an integrated account of how mTORC1 activity influences naive pluripotency through Gsk3. Our study therefore reinforces Gsk3 as the central node and provides a comprehensive, data-rich resource that will improve our understanding of mechanisms regulating pluripotency and stimulate avenues for further mechanistic studies. : Li et al. conducted genome-wide CRISPR screens in mouse ESCs to identify genes affecting maintenance of and exit from naive pluripotency using a Rex1GFP reporter. They show that loss of two mTORC1-negative regulators, Tsc1/2 and Gator1, can cause opposing phenotypes through differential regulation of Gsk3 activity. Keywords: CRISPR, screening, naive pluripotency, exit from pluripotency, Akt, mTORC1, mTORC2, GATOR1, Nprl2, Tsc

Modeling HNF1B-associated monogenic diabetes using human iPSCs reveals an early stage impairment of the pancreatic developmental program.

Heterozygous mutations in HNF1B in humans result in a multisystem disorder, including pancreatic hypoplasia and diabetes mellitus. Here we used a well-controlled human induced pluripotent stem cell pancreatic differentiation model to elucidate the molecular mechanisms underlying HNF1B-associated diabetes. Our results show that lack of HNF1B blocks specification of pancreatic fate from the foregut progenitor (FP) stage, but HNF1B haploinsufficiency allows differentiation of multipotent pancreatic progenitor cells (MPCs) and insulin-secreting β-like cells. We show that HNF1B haploinsufficiency impairs cell proliferation in FPs and MPCs. This could be attributed to impaired induction of key pancreatic developmental genes, including SOX11, ROBO2, and additional TEAD1 target genes whose function is associated with MPC self-renewal. In this work we uncover an exhaustive list of potential HNF1B gene targets during human pancreas organogenesis whose downregulation might underlie HNF1B-associated diabetes onset in humans, thus providing an important resource to understand the pathogenesis of this disease.We thank Prof. Andrew T. Hattersley (Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK) for important discussions orienting the study. S.A.R.-S. is a career investigator from the Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (CONICET). This work was supported by the CONICET/Royal Society International Exchanges Cost Share 2018 (IEC\R2\181023) to L.V. and S.A.R.-S. The S.A.R.-S. laboratory is funded by grants from Agencia Nacional de Promoción Científica y Tecnológica of Argentina (PICT-2015 3605, PICT-2017 2071) and the Universidad de Buenos Aires (UBACYT20020170200156BA). The L.V. laboratory is funded by the ERC advanced grant New-Chol, the core support grant from the Wellcome Trust and Medical Research Council of the Wellcome–MRC Cambridge Stem Cell Institute, and the Cambridge University Hospitals NIHR Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. RHK was funded by the Cambridge Wellcome Trust PhD clinical program, CS by ASTAR studentship, PM, DM, SV, KT, MC by the Sanger Wellcome Institute. E.O. is supported by a PhD fellowship from the CONICET

Genome-wide screening identifies Polycomb repressive complex 1.3 as an essential regulator of human naïve pluripotent cell reprogramming.

Uncovering the mechanisms that establish naïve pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naïve pluripotency by reprogramming are largely unknown. Here, we use genome-wide screening to identify essential regulators as well as major impediments of human primed to naïve pluripotent stem cell reprogramming. We discover that factors essential for cell state change do not typically undergo changes at the level of gene expression but rather are repurposed with new functions. Mechanistically, we establish that the variant Polycomb complex PRC1.3 and PRDM14 jointly repress developmental and gene regulatory factors to ensure naïve cell reprogramming. In addition, small-molecule inhibitors of reprogramming impediments improve naïve cell reprogramming beyond current methods. Collectively, this work defines the principles controlling the establishment of human naïve pluripotency and also provides new insights into mechanisms that destabilize and reconfigure cell identity during cell state transitions

An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS-derived cardiac myocytes

Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular malformation resulting in hypoplasia or atresia of the left ventricle, ascending aorta, and aortic and mitral valves. Diminished flow through the left side of the heart is clearly a key contributor to the condition, but any myocardial susceptibility component is as yet undefined. Using recent advances in the field of induced pluripotent stem cells (iPSCs), we have been able to generate an iPSC model of HLHS malformation and characterize the properties of cardiac myocytes (CMs) differentiated from these and control-iPSC lines. Differentiation of HLHS-iPSCs to cardiac lineages revealed changes in the expression of key cardiac markers and a lower ability to give rise to beating clusters when compared with control-iPSCs and human embryonic stem cells (hESCs). HLHS-iPSC-derived CMs show a lower level of myofibrillar organization, persistence of a fetal gene expression pattern, and changes in commitment to ventricular versus atrial lineages, and they display different calcium transient patterns and electrophysiological responses to caffeine and β-adrenergic antagonists when compared with hESC- and control-iPSC-derived CMs, suggesting that alternative mechanisms to release calcium from intracellular stores such as the inositol trisphosphate receptor may exist in HLHS in addition to the ryanodine receptor thought to function in control-iPSC-derived CMs. Together our findings demonstrate that CMs derived from an HLHS patient demonstrate a number of marker expression and functional differences to hESC/control iPSC-derived CMs, thus providing some evidence that cardiomyocyte-specific factors may influence the risk of HLHS