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）.     

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.     

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.     

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.     

The admiR-able advances in cardiovascular biology through the zebrafish model system

MicroRNAs are small non-coding RNAs endogenously expressed by all tissues during development and adulthood. They regulate gene expression by controlling the stability of targeted messenger RNA. In cardiovascular tissues microRNAs play a role by modulating essential genes involved in heart and blood vessel development and homeostasis. The zebrafish (Danio rerio) system is a recognized vertebrate model system useful to study cardiovascular biology; recently, it has been used to investigate microRNA functions during natural and pathological states. In this review, we will illustrate the advantages of the zebrafish model in the study of microRNAs in heart and vascular cells, providing an update on recent discoveries using the zebrafish to identify new microRNAs and their targeted genes in cardiovascular tissues. Lastly, we will provide evidence that the zebrafish is an optimal model system to undercover new microRNA functions in vertebrates and to improve microRNA-based therapeutic approaches.     

Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.