Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications

The different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos. Our results show that histones carrying canonical cHC modifications are retained in cHC regions of sperm chromatin. These modified histones are transmitted to the oocyte and contribute to the formation of paternal embryonic cHC. Subsequently, the modifications are recognized by the H3K9/HP1 pathway maternal chromatin modifiers and propagated over the embryonic cleavage divisions. These results are in contrast to what has been described for mouse embryos, in which paternal cHC lacks canonical modifications and is initially established by Polycomb group proteins. Our results show intergenerational epigenetic inheritance of the cHC structure in human embryos

Silencing markers are retained on pericentric heterochromatin during murine primordial germ cell development

Background: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins l

Is it possible to detect gravitational waves with atom interferometers?

We investigate the possibility to use atom interferometers to detect gravitational waves. We discuss the interaction of gravitational waves with an atom interferometer and analyze possible schemes

Precision Measurement of the Newtonian Gravitational Constant Using Cold Atoms

About 300 experiments have tried to determine the value of the Newtonian gravitational constant, G, so far, but large discrepancies in the results have made it impossible to know its value precisely. The weakness of the gravitational interaction and the impossibility of shielding the effects of gravity make it very difficult to measure G while keeping systematic effects under control. Most previous experiments performed were based on the torsion pendulum or torsion balance scheme as in the experiment by Cavendish in 1798, and in all cases macroscopic masses were used. Here we report the precise determination of G using laser-cooled atoms and quantum interferometry. We obtain the value G=6.67191(99) x 10^(-11) m^3 kg^(-1) s^(-2) with a relative uncertainty of 150 parts per million (the combined standard uncertainty is given in parentheses). Our value differs by 1.5 combined standard deviations from the current recommended value of the Committee on Data for Science and Technology. A conceptually different experiment such as ours helps to identify the systematic errors that have proved elusive in previous experiments, thus improving the confidence in the value of G. There is no definitive relationship between G and the other fundamental constants, and there is no theoretical prediction for its value, against which to test experimental results. Improving the precision with which we know G has not only a pure metrological interest, but is also important because of the key role that G has in theories of gravitation, cosmology, particle physics and astrophysics and in geophysical models.Comment: 3 figures, 1 tabl

Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation

In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling and contain the lysine-63 linkage-specific BRCC36 subunit that is functionalized by scaffold subunits ABRAXAS and ABRO1, respectively. The molecular basis underlying BRCA1-A and BRISC function is currently unknown. Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2α, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains. Our work explains modularity in the BRCC36 DUB family, with different adaptor subunits conferring diversified targeting and regulatory functions.ISSN:1097-2765ISSN:1097-416

Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis

<p>Abstract</p> <p>Background</p> <p><it>Tropheryma whipplei</it>, the agent of Whipple's disease, causes localised infections in the absence of histological digestive involvement. Our objective is to describe <it>T. whipplei </it>encephalitis.</p> <p>Methods</p> <p>We first diagnosed a patient presenting dementia and obesity whose brain biopsy and cerebrospinal fluid specimens contained <it>T. whipplei </it>DNA and who responded dramatically to antibiotic treatment. We subsequently tested cerebrospinal fluid specimens and brain biopsies sent to our laboratory using <it>T. whipplei </it>PCR assays. PAS-staining and <it>T. whipplei </it>immunohistochemistry were also performed on brain biopsies. Analysis was conducted for 824 cerebrospinal fluid specimens and 16 brain biopsies.</p> <p>Results</p> <p>We diagnosed seven patients with <it>T. whipplei </it>encephalitis who demonstrated no digestive involvement. Detailed clinical histories were available for 5 of them. Regular PCR that targeted a monocopy sequence, PAS-staining and immunohistochemistry were negative; however, several highly sensitive and specific PCR assays targeting a repeated sequence were positive. Cognitive impairments and ataxia were the most common neurologic manifestations. Weight gain was paradoxically observed for 2 patients. The patients' responses to the antibiotic treatment were dramatic and included weight loss in the obese patients.</p> <p>Conclusions</p> <p>We describe a new clinical condition in patients with dementia and obesity or ataxia linked to <it>T. whipplei </it>that may be cured with antibiotics.</p