Initiation

Summary

Initiation is a rite of passage marking entrance or acceptance into a group or society. It could also be a formal admission to adulthood in a community or one of its formal components. In an extended sense, it can also signify a transformation in which the initiate is 'reborn' into a new role. Examples of initiation ceremonies might include Christian baptism or confirmation, Jewish bar or bat mitzvah, acceptance into a fraternal organization, secret society or religious order, or graduation from school or recruit training. A person taking the initiation ceremony in traditional rites, such as those depicted in these pictures, is called an initiate. See also rite of passage. Characteristics William Ian Miller notes the role of ritual humiliation in comic ordering and testing. Mircea Eliade discussed initiation as a principal religious act by classical or traditional societies. He defined initiation as "a basic change in existential condition", which liberates man from profane

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https://en.wikipedia.org/wiki/Initiation

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Lung cancers represent the leading cause of cancer-related deaths worldwide. These pulmonary cancers count several histological subgroups, whose non-small cell lung cancers, subject of our study. We were precisely interested in the most common subtype of non-small cell lung cancers, the adenocarcinomas, that are frequently mutated for the oncogene Kras and the tumor suppressors Tp53 and Lkb1. These tumors seeking to ensure their survival and their uncontrolled proliferation, especially modify their metabolism to sustain their increased and essential nutrient requirements. These cancer cells thus overexpress glucose transporters to augment their sugar uptake and maintain their functions. Although the high expression of certain transporters in pulmonary adenocarcinomas is associated with a poor vital prognostic, their implication in tumorigenesis remains poorly understood. Also, we focused on the two most expressed transporters in lung adenocarcinomas, GLUT1 and GLUT3, to determine and understand their putative role in the tumor cell-of-origin, but also in the initiation and growth of adenocarcinomas. To investigate these questions in vivo, we used genetically engineered mouse models, based on the frequent genetic alterations Kras, Tp53 and Lkb1. These models closely mimic human non-small cell lung cancer development. The intratracheal instillation of these mice with viral particles expressing Cre-recombinase allows the genetic recombinations and the subsequent initiation of pulmonary tumors. Being interesting in glucose transporters, we interbred the murine models KrasLSL-G12D/WT (K), KrasLSL-G12D/WT; Tp53lox/lox (KP), and KrasLSL-G12D/WT; Lkb1lox/lox (KL) with the models Slc2a1lox/lox (G1) and/or Slc2a3lox/lox (G3). Thus, we could specifically initiate the development of tumors expressing the oncogenic mutation KrasG12D, the deletion or not of Tp53 or Lkb1, and with or without glucose transporter Glut1 and/or Glut3. Our in vivo study then revealed that the only deletion of Glut1 in tumor cells was insufficient to impair their growth, and this, independently of the cell-of-origin or the stage of the lesions. Using electron microscopy and 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS), we demonstrated that the glucose-derived biomass accumulated into lamellar body-like organelles of the tumor cells. Moreover, this accumulation partially depends on Glut1. Ex vivo analyses showed besides that glycolysis in cancer cells was diminished in Glut1 absence, except when Glut3 was highly expressed. Similarly to Glut1, Glut3 expression suppression in cancer cells affects neither the initiation, nor the tumor expansion. In contrast, the combined deletion of Glut1 and Glut3 significantly decreases non-small cell lung cancer growth. Our results demonstrate the requirement to target both glucose transporters to impair pulmonary adenocarcinomas tumorigenesis.

EPFL2020

Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy

Thierry Buclin, Jacques Fellay, Monia Guidi, Christian Hammer, Christian Axel Wandall Thorball

Objective. There is limited data on abdominal obesity and the influence of genetics on weight change after ant iretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS). Methods. Mixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background. Results. Individuals with CD4 nadir = 200, and 2.8 times more WHR than individuals with >= 100 (P < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir = 200 (OR, 1.69; 95% CI, 1.26-2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir = 100 (OR, 1.35; 95% CI, 1.17-1.54 [in men]; OR, 1.36; 95% CI, 1.18-1.57 [in women]), persisting after 10 years of ART No significant differences were found across antiretroviral drug classes or genetic scores. Conclusions. The risk of general and abdominal obesity increased with CD4 nadir

OXFORD UNIV PRESS INC2020

Influence of Rotational Nucleosome Positioning on Transcription Start Site Selection in Animal Promoters

Giovanna Ambrosini, Philipp Bucher, René Dreos

The recruitment of RNA-Pol-II to the transcription start site (TSS) is an important step in gene regulation in all organisms. Core promoter elements (CPE) are conserved sequence motifs that guide Pol-II to the TSS by interacting with specific transcription factors (TFs). However, only a minority of animal promoters contains CPEs. It is still unknown how Pol-II selects the TSS in their absence. Here we present a comparative analysis of promoters’ sequence composition and chromatin architecture in five eukaryotic model organisms, which shows the presence of common and unique DNA-encoded features used to organize chromatin. Analysis of Pol-II initiation patterns uncovers that, in the absence of certain CPEs, there is a strong correlation between the spread of initiation and the intensity of the 10 bp periodic signal in the nearest downstream nucleosome. Moreover, promoters’ primary and secondary initiation sites show a characteristic 10 bp periodicity in the absence of CPEs. We also show that DNA natural variants in the region immediately downstream the TSS are able to affect both the nucleosome-DNA affinity and Pol-II initiation pattern. These findings support the notion that, in addition to CPEs mediated selection, sequence–induced nucleosome positioning could be a common and conserved mechanism of TSS selection in animals

Public Library Science2016

EPFL2020