Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin.

Post-translational modifications of histone amino termini are an important regulatory mechanism that induce transitions in chromatin structure, thereby contributing to epigenetic gene control and the assembly of specialized chromosomal subdomains. Methylation of histone H3 at lysine 9 (H3-Lys9) by site-specific histone methyltransferases (Suv39h HMTases) marks constitutive heterochromatin. Here, we show that H3-Lys9 methylation also occurs in facultative heterochromatin of the inactive X chromosome (Xi) in female mammals. H3-Lys9 methylation is retained through mitosis, indicating that it might provide an epigenetic imprint for the maintenance of the inactive state. Disruption of the two mouse Suv39h HMTases abolishes H3-Lys9 methylation of constitutive heterochromatin but not that of the Xi. In addition, HP1 proteins, which normally associate with heterochromatin, do not accumulate with the Xi. These observations suggest the existence of an Suv39h-HP1-independent pathway regulating H3-Lys9 methylation of facultative heterochromatin.     

Ultra-high suppression microwave photonic bandstop filters

A bandstop radio frequency （RF） filter can enhance the capabilities of RF communication systems by removing unwanted signal components such as distortion, or interference. In modem cognitive radio systems, frequency agile filters are desired to block interferers with dynamically changing frequencies and powers. These filters should be tunable over a broad frequency range, and they should be capable of suppressing very strong signals with a high resolution. To simultaneously meet these requirements with traditional RF filters are highly chal- lenging. Microwave photonic （MWP）, a technology that primary deals with the generation, distribution, and processing of high speed RF signals using photonic techniques and components, is promising for creating frequency agile RF filters. However, traditional MWP filters are lacking the high resolution and peak suppression exhibited by state-of-the-art RF electrical filters. We recently introduced a new class of MWP notch filter which is free from this limitation. This scheme allowed the creation of anomalously high suppression MWP notch filter from virtually any kind of optical resonance, irrespective of its type （gain or absorp tion）, or its magnitude. This enabled, for the first time, simultaneous optimization of the MWP filter resolution, peak attenuation, and frequency tuning range. In this paper, we present the analysis of notch filter response creation using the novel sideband processing technique. We then show the applicability of this technique to a wide range of optical filters. We compare simulated and experimental results of the notch filter response created using three types of optical filter commonly used in MWP signal processing, namely stimulated Brillouin scattering （SBS）, an integrated optical ring resonator （ORR）, and a phase-shifted fiber Bragg-grating （FBG）.     

Thresholds for Cenozoic bipolar glaciation

The long-standing view of Earth's Cenozoic glacial history calls for the first continental-scale glaciation of Antarctica in the earliest Oligocene epoch ( approximately 33.6 million years ago), followed by the onset of northern-hemispheric glacial cycles in the late Pliocene epoch, about 31 million years later. The pivotal early Oligocene event is characterized by a rapid shift of 1.5 parts per thousand in deep-sea benthic oxygen-isotope values (Oi-1) within a few hundred thousand years, reflecting a combination of terrestrial ice growth and deep-sea cooling. The apparent absence of contemporaneous cooling in deep-sea Mg/Ca records, however, has been argued to reflect the growth of more ice than can be accommodated on Antarctica; this, combined with new evidence of continental cooling and ice-rafted debris in the Northern Hemisphere during this period, raises the possibility that Oi-1 represents a precursory bipolar glaciation. Here we test this hypothesis using an isotope-capable global climate/ice-sheet model that accommodates both the long-term decline of Cenozoic atmospheric CO(2) levels and the effects of orbital forcing. We show that the CO(2) threshold below which glaciation occurs in the Northern Hemisphere ( approximately 280 p.p.m.v.) is much lower than that for Antarctica ( approximately 750 p.p.m.v.). Therefore, the growth of ice sheets in the Northern Hemisphere immediately following Antarctic glaciation would have required rapid CO(2) drawdown within the Oi-1 timeframe, to levels lower than those estimated by geochemical proxies and carbon-cycle models. Instead of bipolar glaciation, we find that Oi-1 is best explained by Antarctic glaciation alone, combined with deep-sea cooling of up to 4 degrees C and Antarctic ice that is less isotopically depleted (-30 to -35 per thousand) than previously suggested. Proxy CO(2) estimates remain above our model's northern-hemispheric glaciation threshold of approximately 280 p.p.m.v. until approximately 25 Myr ago, but have been near or below that level ever since. This implies that episodic northern-hemispheric ice sheets have been possible some 20 million years earlier than currently assumed (although still much later than Oi-1) and could explain some of the variability in Miocene sea-level records.     

Fate choice of post-natal mesoderm progenitors: skeletal versus cardiac muscle plasticity

Regenerative medicine for skeletal and cardiac muscles still constitutes a fascinating and ambitious frontier. In this perspective, understanding the possibilities of intrinsic cell plasticity, present in post-natal muscles, is vital to define and improve novel therapeutic strategies for acute and chronic diseases. In addition, many somatic stem cells are now crossing the boundaries of basic/translational research to enter the first clinical trials. However, it is still an open question whether a lineage switch between skeletal and cardiac adult myogenesis is possible. Therefore, this review focuses on resident somatic stem cells of post-natal skeletal and cardiac muscles and their plastic potential toward the two lineages. Furthermore, examples of myogenic lineage switch in adult stem cells are also reported and discussed.     

Past extreme warming events linked to massive carbon release from thawing permafrost

Between about 55.5 and 52 million years ago, Earth experienced a series of sudden and extreme global warming events (hyperthermals) superimposed on a long-term warming trend. The first and largest of these events, the Palaeocene-Eocene Thermal Maximum (PETM), is characterized by a massive input of carbon, ocean acidification and an increase in global temperature of about 5 °C within a few thousand years. Although various explanations for the PETM have been proposed, a satisfactory model that accounts for the source, magnitude and timing of carbon release at the PETM and successive hyperthermals remains elusive. Here we use a new astronomically calibrated cyclostratigraphic record from central Italy to show that the Early Eocene hyperthermals occurred during orbits with a combination of high eccentricity and high obliquity. Corresponding climate-ecosystem-soil simulations accounting for rising concentrations of background greenhouse gases and orbital forcing show that the magnitude and timing of the PETM and subsequent hyperthermals can be explained by the orbitally triggered decomposition of soil organic carbon in circum-Arctic and Antarctic terrestrial permafrost. This massive carbon reservoir had the potential to repeatedly release thousands of petagrams (10(15) grams) of carbon to the atmosphere-ocean system, once a long-term warming threshold had been reached just before the PETM. Replenishment of permafrost soil carbon stocks following peak warming probably contributed to the rapid recovery from each event, while providing a sensitive carbon reservoir for the next hyperthermal. As background temperatures continued to rise following the PETM, the areal extent of permafrost steadily declined, resulting in an incrementally smaller available carbon pool and smaller hyperthermals at each successive orbital forcing maximum. A mechanism linking Earth's orbital properties with release of soil carbon from permafrost provides a unifying model accounting for the salient features of the hyperthermals.     

SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood. Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α (HIFs). SHARP1 opposes HIF-dependent TNBC cell migration in vitro, and invasive or metastatic behaviours in vivo. SHARP1 is required, and sufficient, to limit expression of HIF-target genes. In primary TNBC, endogenous SHARP1 levels are inversely correlated with those of HIF targets. Mechanistically, SHARP1 binds to HIFs and promotes HIF proteasomal degradation by serving as the HIF-presenting factor to the proteasome. This process is independent of pVHL (von Hippel-Lindau tumour suppressor), hypoxia and the ubiquitination machinery. SHARP1 therefore determines the intrinsic instability of HIF proteins to act in parallel to, and cooperate with, oxygen levels. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and metastatic propensity.