132,907 research outputs found
The multicopy gene Sly represses the sex chromosomes in the male mouse germline after meiosis.
No full textStudies of mice with Y chromosome long arm deficiencies suggest that the male-specific region (MSYq) encodes information required for sperm differentiation and postmeiotic sex chromatin repression (PSCR). Several genes have been identified on MSYq, but because they are present in more than 40 copies each, their functions cannot be investigated using traditional gene targeting. Here, we generate transgenic mice producing small interfering RNAs that specifically target the transcripts of the MSYq-encoded multicopy gene Sly (Sycp3-like Y-linked). Microarray analyses performed on these Sly-deficient males and on MSYq-deficient males show a remarkable up-regulation of sex chromosome genes in spermatids. SLY protein colocalizes with the X and Y chromatin in spermatids of normal males, and Sly deficiency leads to defective repressive marks on the sex chromatin, such as reduced levels of the heterochromatin protein CBX1 and of histone H3 methylated at lysine 9. Sly-deficient mice, just like MSYq-deficient mice, have severe impairment of sperm differentiation and are near sterile. We propose that their spermiogenesis phenotype is a consequence of the change in spermatid gene expression following Sly deficiency. To our knowledge, this is the first successful targeted disruption of the function of a multicopy gene (or of any Y gene). It shows that SLY has a predominant role in PSCR, either via direct interaction with the spermatid sex chromatin or via interaction with sex chromatin protein partners. Sly deficiency is the major underlying cause of the spectrum of anomalies identified 17 y ago in MSYq-deficient males. Our results also suggest that the expansion of sex-linked spermatid-expressed genes in mouse is a consequence of the enhancement of PSCR that accompanies Sly amplification
A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.
No full textIntragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked multicopy genes has long been suggested but never demonstrated. The Y-encoded multicopy gene Sly has been shown to have a predominant role in the epigenetic repression of post meiotic sex chromatin (PMSC) and, as such, represses X and Y genes, among which are its X-linked homologs Slx and Slxl1. Here, we produced mice that are deficient for both Sly and Slx/Slxl1 and observed that Slx/Slxl1 has an opposite role to that of Sly, in that it stimulates XY gene expression in spermatids. Slx/Slxl1 deficiency rescues the sperm differentiation defects and near sterility caused by Sly deficiency and vice versa. Slx/Slxl1 deficiency also causes a sex ratio distortion towards the production of male offspring that is corrected by Sly deficiency. All in all, our data show that Slx/Slxl1 and Sly have antagonistic effects during sperm differentiation and are involved in a postmeiotic intragenomic conflict that causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouse X and Y chromosomes. It may also be at the basis of cases of F1 male hybrid sterility where the balance between Slx/Slxl1 and Sly copy number, and therefore expression, is disrupted. To the best of our knowledge, our work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the concept that intragenomic conflict is an important evolutionary force which impacts on gene expression, genome structure, and speciation
Scotney: an archaeological survey and map analysis
No full textThis edited volume sets out the work of a team of scholars from Northwestern University and the University of Southampton led by Matthew Johnson, in collaboration with the National Trust. Between 2010 and 2014, different members of the group carried out topographical, geophysical and building survey at four different late medieval sites and landscapes in south-eastern England, all owned and managed by the National Trust: Bodiam, Scotney, Knole and Ightham. Studies were also undertaken into documentary, map and other evidence. A particularly important element of the research was to synthesise and re-present the ‘grey literature’ at all four sites. This volume seeks to present this work and discuss its archaeological and historical importance. It places the four sites and their landscapes in their setting, as part of the wider landscape of south-east England. It discusses the importance of these places in understanding later medieval elite sites and landscapes in general, and in terms of their long-term biographies and contexts. Central to the volume are the linked ideas of lived experience and political ecology in presenting a new understanding of late medieval sites and landscapes
Extinction of the contact process on Small World Graphs
No full textWe study the contact process, which can be used to model infections, and its extinction on small-world graphs. Such graphs where first introduced by Watts and
Strogatz and can be used to model social networks. In particular, we work with a graph that is a large torus (Z mod R)^d with some additional random edges. As
R → ∞, we examine the local limit of this graph. Here, every point is on a Z^d lattice and has additional edges distributed by ξ, where ξ has exponential tails. We follow
the methods of Bhamidi, Nam, Nguyen and Sly, for proving recursive extinction on Galton Watson trees with offspring of exponential tails, and combine this with clustering methods suggested by M ́enard and Singh [6] for controlling the contact process on random graphs. Putting these two ideas together, we show that for a small enough infection rate, the contact process extinct almost surely on our small-world graphs
Seasonal immune modulation in humans: Observed patterns and potential environmental drivers
No full textLink to a related website: https://espace.library.uq.edu.au/view/UQ:347935/UQ347935_OA.pdf, Open Access via UnpaywallAbstract not availableStuart Paynter, Robert S. Ware, Peter D. Sly, Gail Williams, Philip Weinstei
The effect of the mutation of important functional domains in the murine lymphocyte specific adaptor protein SLY on the immune system
No full textSLY ist das Lymphozyten-spezifische Adaptorprotein der SLY Proteinfamilie, zu der noch SLY2 und SASH1 gehören. Nach Stimulation des Antigenrezeptors wird SLY phosphoryliert und somit aktiviert. Die Funktion von SLY im Immunsystem war bisher noch unbekannt und sollte durch Analyse des Slyd/d-Mausstammes im Rahmen dieser Arbeit aufgeklärt werden. Die eingeführte Mutation führte zur Produktion eines verkürzten Proteins SLYd, dem Teile wichtiger Funktionseinheiten fehlten. Durch in vitro und in vivo Versuche konnte festgestellt werden, dass SLY sowohl bei Immunantworten gegen T-Zell abhängige, als auch gegen T-Zell unabhängige Antigene eine wichtige Rolle spielt. Die T- und B-Zell Entwicklung und Funktion sind durch die Mutation in SLY beeinträchtigt und somit die Funktion des Immunsystems.SLY is the lymphocyte-specific adaptor protein of the SLY protein family. The family contains SLY, SLY2 and SASH1. After antigen receptor stimulation, SLY gets phosphorylated and activated. The function of SLY in the immune system was unknown, so the mutated mouse Slyd/d was created and analyzed. The truncated protein Slyd lacks part of the functional domains. In vitro and in vivo studies showed, that wildtype SLY is required for the development and function of T and B cells. It is also essential for the activation of the immune system against T cell dependent and independent antigens
Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.
No full textThe human and mouse sex chromosomes are enriched in multicopy genes required for postmeiotic differentiation of round spermatids into sperm. The gene Sly is present in multiple copies on the mouse Y chromosome and encodes a protein that is required for the epigenetic regulation of postmeiotic sex chromosome expression. The X chromosome carries two multicopy genes related to Sly: Slx and Slxl1. Here we investigate the role of Slx/Slxl1 using transgenically-delivered small interfering RNAs to disrupt their function. We show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. Slx/Slxl1 deficiency leads to delay in spermatid elongation and sperm release. A high proportion of delayed spermatids are eliminated via apoptosis, with a consequent reduced sperm count. The remaining spermatozoa are abnormal with impaired motility and fertilizing abilities. Microarray analyses reveal that Slx/Slxl1 deficiency affects the metabolic processes occurring in the spermatid cytoplasm but does not lead to a global perturbation of sex chromosome expression; this is in contrast with the effect of Sly deficiency which leads to an up-regulation of X and Y chromosome genes. This difference may be due to the fact that SLX/SLXL1 are cytoplasmic while SLY is found in the nucleus and cytoplasm of spermatids
- …
