Securin Is Not Required for Chromosomal Stability in Human Cells

Abnormalities of chromosome number are frequently observed in cancers. The mechanisms regulating chromosome segregation in human cells are therefore of great interest. Recently it has been reported that human cells without an hSecurin gene lose chromosomes at a high frequency. Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect. After a few passages hSecurin(−/−) cells became chromosomally stable and executed mitoses normally. This was unexpected, as the securin loss resulted in a persisting reduction of the sister-separating protease separase and inefficient cleavage of the cohesin subunit Scc1. Our data demonstrate that securin is dispensable for chromosomal stability in human cells. We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation

Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1

The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) that seems to extend the RNA-binding surface to six nucleotides for SF1 (Homo sapiens) and seven nucleotides for GLD-1 (Caenorhabditis elegans). To understand the structural basis of this probable difference in specificity, we determined the solution structure of GLD-1 KH-QUA2 with the complete consensus sequence identified in the tra-2 gene. Compared to SF1, the GLD-1 KH-QUA2 interface adopts a different conformation resulting indeed in an additional sequence-specific binding pocket for a uracil at the 5′end. The functional relevance of this binding pocket is emphasized by our bioinformatics analysis showing that GLD-1 binding sites with this 5′end uracil are more predictive for the functional response of the messenger RNAs to gld-1 knockout. We further reveal the importance of the KH-QUA2 interface in vitro and that its alteration in vivo affects the level of translational repression dependent on the sequence of the GLD-1 binding motif. In conclusion, we demonstrate that the QUA2 domain distinguishes GLD-1 from other members of the STAR family and contributes more generally to the modulation of RNA-binding affinity and specificity of KH domain containing protein

Prototypes and Stereotypes in the Intersectional Representation of Gender, Race, and Sexual Orientation Categories

Chapter 1: Category prototypes, prevalence, and social status: Intersectional representations of gender and race categories in Italy, United States, and South Africa. We analyzed (pre-registered Pilot, Study 1-3; in Italy, the US, and South Africa) prototypical representations, perceived base rates, and status of race (White and Black people) and gender (men and women) categories to understand how androcentrism and ethnocentrism intersect. White and Black people were prototyped as men, and especially for Black people, across countries. Men and women were prototyped as White across countries, and especially for women, in the US and Italy (Pilot). In Italy and the US, participants overestimated the base rates of White men among men and White people, while in South Africa they estimated higher prevalence of Black over White people and men over women. In Italy and South Africa, participants particularly overestimated the salaries of White men among men and White people, while US participants estimated higher salaries for White over Black people and men over women. Results are discussed in light of the intersectionality literature. Chapter 2: Intersectional Asymmetry in the Cognitive Combination of Gay Men and Black Men. The current studies addressed the strength of oppositional stereotypes between Black men and gay men (Study 1-2) and the manner in which perceivers combine stereotypes about Black men and gay men (Study 3). As pre-registered, in Study 1, a conjunction fallacy effect was produced both through cuing stereotypes of Black men (Study 1a) and gay men (Study 1b). In Study 2, we used a within-subject design as a more stringent test of the conjunction fallacy effect. Although not pre-registered, a clear asymmetry emerged: the conjunction fallacy effect was stronger when stereotypes of Black men were cued (Study 2a), than when stereotypes of gay men were cued (Study 2b). Study 2, and in part Study 1, suggested that it is easier to cognitively combine the categories “Black men” and “gay men” if a target is stereotyped as a gay man than if he is stereotyped as a Black man. Guided by the suggested asymmetry, we found that in an updating paradigm, the category “Black” more easily integrated with gay than “gay” with Black. The novelty of the current research lies in the investigation of the directionality of this cognitive combination.Chapter 1: Category prototypes, prevalence, and social status: Intersectional representations of gender and race categories in Italy, United States, and South Africa. We analyzed (pre-registered Pilot, Study 1-3; in Italy, the US, and South Africa) prototypical representations, perceived base rates, and status of race (White and Black people) and gender (men and women) categories to understand how androcentrism and ethnocentrism intersect. White and Black people were prototyped as men, and especially for Black people, across countries. Men and women were prototyped as White across countries, and especially for women, in the US and Italy (Pilot). In Italy and the US, participants overestimated the base rates of White men among men and White people, while in South Africa they estimated higher prevalence of Black over White people and men over women. In Italy and South Africa, participants particularly overestimated the salaries of White men among men and White people, while US participants estimated higher salaries for White over Black people and men over women. Results are discussed in light of the intersectionality literature. Chapter 2: Intersectional Asymmetry in the Cognitive Combination of Gay Men and Black Men. The current studies addressed the strength of oppositional stereotypes between Black men and gay men (Study 1-2) and the manner in which perceivers combine stereotypes about Black men and gay men (Study 3). As pre-registered, in Study 1, a conjunction fallacy effect was produced both through cuing stereotypes of Black men (Study 1a) and gay men (Study 1b). In Study 2, we used a within-subject design as a more stringent test of the conjunction fallacy effect. Although not pre-registered, a clear asymmetry emerged: the conjunction fallacy effect was stronger when stereotypes of Black men were cued (Study 2a), than when stereotypes of gay men were cued (Study 2b). Study 2, and in part Study 1, suggested that it is easier to cognitively combine the categories “Black men” and “gay men” if a target is stereotyped as a gay man than if he is stereotyped as a Black man. Guided by the suggested asymmetry, we found that in an updating paradigm, the category “Black” more easily integrated with gay than “gay” with Black. The novelty of the current research lies in the investigation of the directionality of this cognitive combination

Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes

The cold shock domain is one of the most highly conserved motifs between bacteria and higher eukaryotes. Y-box-binding proteins represent a subfamily of cold shock domain proteins with pleiotropic functions, ranging from transcription in the nucleus to translation in the cytoplasm. These proteins have been investigated in all major model organisms except Caenorhabditis elegans. In this study, we set out to fill this gap and present a functional characterization of CEYs, the C. elegans Y-box-binding proteins. We find that, similar to other organisms, CEYs are essential for proper gametogenesis. However, we also report a novel function of these proteins in the formation of large polysomes in the soma. In the absence of the somatic CEYs, polysomes are dramatically reduced with a simultaneous increase in monosomes and disomes, which, unexpectedly, has no obvious impact on animal biology. Because transcripts that are enriched in polysomes in wild-type animals tend to be less abundant in the absence of CEYs, our findings suggest that large polysomes might depend on transcript stabilization mediated by CEY protein

Ribonuclease-mediated control of body fat

Obesity is a global health issue, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention, and key transcription factors involved in lipid metabolism, such as SBP-1/SREBP, LPD-2/C/EBP, and MDT-15, are conserved from nematodes to mammals. However, there is a growing awareness that lipid metabolism can also be controlled by post-transcriptional mechanisms. Here, we show that the Caenorhabditis elegans RNase, REGE-1, related to MCPIP1/Zc3h12a/Regnase-1, a key regulator of mammalian innate immunity, promotes accumulation of body fat. Using exon-intron split analysis, we find that REGE-1 promotes fat by degrading the mRNA encoding ETS-4, a fat-loss-promoting transcription factor. Because ETS-4, in turn, induces rege-1 transcription, REGE-1 and ETS-4 appear to form an auto-regulatory module. We propose that this type of fat regulation may be of key importance when, if faced with an environmental change, an animal must rapidly but precisely remodel its metabolism.</p

CENP-E as an Essential Component of the Mitotic Checkpoint In Vitro

AbstractAccurate chromatid separation is monitored by a checkpoint mechanism that delays anaphase onset until all centromeres are correctly attached to the mitotic spindle. Using Xenopus egg extracts, the kinetochore-associated microtubule motor protein CENP-E is now found to be required for establishing and maintaining this checkpoint. When CENP-E function is disrupted by immunodepletion or antibody addition, extracts fail to arrest in response to spindle damage. Mitotic arrest can be restored by addition of high levels of soluble MAD2, demonstrating that the absence of CENP-E eliminates kinetochore-dependent signaling but not the downstream steps in checkpoint signal transduction. Because it directly binds both to spindle microtubules and to the kinetochore-associated checkpoint kinase BUBR1, CENP-E is a central component in the vertebrate checkpoint that modulates signaling activity in a microtubule-dependent manner

A Cognitive Look at the "Invisibility" of Older Gay Men Within the Categories 'Gay Man' and 'Elderly Man'

Two studies analyzed whether, at the cognitive level, 'Elderly gay man' is "invisible" both when processing the labels 'Gay man' and 'Elderly man'. We suggest that 'Gay man' is conflated with 'Young man', and that 'Elderly man' is conflated with 'Heterosexual man'. Contact with elderly gay men did not alter the perception of 'Gay man' as prevalently young but weakened the perception of 'Elderly man' as heterosexual by default

Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons

Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling