Genomic SELEX for Hfq-binding RNAs identifies genomic aptamers predominantly in antisense transcripts

An unexpectedly high number of regulatory RNAs have been recently discovered that fine-tune the function of genes at all levels of expression. We employed Genomic SELEX, a method to identify protein-binding RNAs encoded in the genome, to search for further regulatory RNAs in Escherichia coli. We used the global regulator protein Hfq as bait, because it can interact with a large number of RNAs, promoting their interaction. The enriched SELEX pool was subjected to deep sequencing, and 8865 sequences were mapped to the E. coli genome. These short sequences represent genomic Hfq-aptamers and are part of potential regulatory elements within RNA molecules. The motif 5′-AAYAAYAA-3′ was enriched in the selected RNAs and confers low-nanomolar affinity to Hfq. The motif was confirmed to bind Hfq by DMS footprinting. The Hfq aptamers are 4-fold more frequent on the antisense strand of protein coding genes than on the sense strand. They were enriched opposite to translation start sites or opposite to intervening sequences between ORFs in operons. These results expand the repertoire of Hfq targets and also suggest that Hfq might regulate the expression of a large number of genes via interaction with cis-antisense RNAs

Thermal Conductivity of Taylor Phase Al3(Mn,Pd) Complex Metallic Alloys

Thermal conductivity, kappa, of Taylor phase T-Al73Mn27-xPdx (x = 0, 2, 4, 6) complex metallic alloys (CMAs) has been studied in the temperature interval from 2 K to 300 K. The characteristics of kappa are typical for the CMAs: a relatively small value, a change of slope at about 50 K and an increase of slope above 100 K. The value of kappa is between 2.7 W/m K and 3.7 W/m K at room temperature. The low thermal conductivity has it's origin in a complex structure: aperiodic on a short length scale, which leads to frequent electron scattering (i.e. to a low electronic contribution to the thermal conductivity), while the large lattice constant defines a small Brillouin zone that enhances umklapp scattering of extended phonons. Above 100 K the non-extended (localized) lattice vibrations are thermally excited, and hopping gives a new heat carrying channel resulting in typical increase of the thermal conductivity with temperature

Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis

Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis. The rationale for a combined molecule is to block the PD-1/PD-L1 interaction between tumor cells and immune cell infiltrate and simultaneously reduce or eliminate TGFβ from the tumor microenvironment. In this study, we explored the effect of M7824 on invasive urothelial carcinoma cell lines