A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression

Abstract: Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. We demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3. Accordingly, we found that HDAC inhibiting proteins from human herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that virally mediated HDAC inhibition can act as a signal for the host to activate NK-cell recognition. DOI: 10.7554/eLife.14749.001

http://derisilab.ucsf.edu/pdfs/e14749-download.pdf

Pancreatic cancer biomarker bolsters nanoparticle-based diagnostic

Arizona State University’s Ye (Tony) Hu and his colleagues have delivered what they hope will be a double dose of good news for detecting pancreatic cancer. Pancreatic cancer is one of the leading causes of cancer deaths because it often goes undetected in early stages, according to the Mayo Clinic.

The researchers report a rapid and inexpensive nanoparticle-based diagnostic fueled, in part, by their second finding, a biomarker on the surface of vesicles released by pancreatic tumors (Nat. Biomed. Eng. 2017, DOI: 10.1038/s41551-016-0021).  Rest

DNA nanotubes self-assemble into molecular bridges between cells

In a microscopic feat that resembled a high-wire circus act, Johns Hopkins researchers have coaxed DNA nanotubes to assemble themselves into bridge-like structures arched between two molecular landmarks on the surface of a lab dish. This self-assembling bridge process, which may someday be used to connect electronic medical devices to living cells, was reported by the team recently in the journal Nature Nanotechnology. Rest

Noble Prize for Ben Feringa

The University of Groningen (a university I had the pleasure of visiting several years ago) news article. An excerpt below:

Feringa is internationally recognized as a pioneer in the field of molecular engines, as the many citations in a background article on nano engines in Nature confirm. One of the potential applications of his engines is the delivery of medication inside the human body. Besides molecular engines, Feringa is also involved in catalysis and smart medication that can, for instance, be turned on and off by light.”

Researchers develop DNA-based single-electron electronic devices

Nature has inspired generations of people, offering a plethora of different materials for innovations. One such material is the molecule of the heritage, or DNA, thanks to its unique self-assembling properties. Researchers at the Nanoscience Center (NSC) of the University of Jyväskylä and BioMediTech (BMT) of the University of Tampere have now demonstrated a method to fabricate electronic devices by using DNA. The DNA itself has no part in the electrical function, but acts as a scaffold for forming a linear, pearl-necklace-like nanostructure consisting of three gold nanoparticles. …

Gold nanoparticles are attached directly within the aqueous solution onto a DNA structure designed and previously tested by the involved groups. The whole process is based on DNA self-assembly, and yields countless of structures within a single patch. Ready structures are further trapped for measurements by electric fields.  Rest

Rebuilding the Building Blocks of Life

Rather than redesigning naturally occurring sequences, researchers employing protein de novo design use peptides that assemble and fold into protein-like structures, relying on two self-assembly principles: The first is peptide-based [1] and incorporates a coiled coil where the resulting folding profile is much easier to predict, helping scientists overcome a common headache in protein design.

The second principle utilizes oligonucleotides (ON),which are widely used in nanotechnology to generate higher-level structures [2], for example in DNA origami. What would happen if researchers combined both principles in the same design? In a new proof-of-concept paper recently published in Nature Communications, Wengel’s team answered this question while designing a novel class of artificial proteins [3]. Rest

Tiny Creatures May Hold Clues to Bolstering Health of Human Cells

Microscopic creatures called tardigrades are among the most resilient animals on Earth, able to survive against extreme temperatures, dehydration and even the harsh conditions of space.

A paper published Tuesday in the journal Nature Communications offers new clues to tardigrades’ toughness and addresses a continuing debate over how these unusual animals evolved. Rest (WSJ paywall)

Project on Genome Editing (OECD BNCT)

The genome editing project of the OECD Working Party on Biotechnology, Nanotechnology and Converging Technologies (BNCT) aims to produce a forum conducive to evidence-based discussion aross countries on the many issues of shared concern. The initiative aims to help guide policy at the national and international levels and promote — where appropriate — cooperative governance approaches. Rest

New CRISPR-like Defense Strategy Discovered in Giant Viruses

When scientists first encountered Mimivirus within amoebae, they thought it was a bacterium because of its size. Much to their surprise, electron microscopy revealed that the organism infecting these amoebae was in fact giant viruses. “A giant virus is like a bacterium but with a capsid and without ribosomes. This is the only difference,” said Bernard La Scola from Aix-Marseille University, who helped discover the virus.

Seven years ago, La Scola’s team realized that this giant virus could be infected by a smaller virus—a virophage called Sputnik. Later they discovered another virophage called Zamilon. Now, using this virophage as a unique tool, the team has discovered a CRISPR-like defense system, the Mimivirus virophage resistance element (MIMIVIRE), which they described in Nature. Rest

Alzheimer’s fibrils

Two research teams have independently obtained atomic-resolution structures of fully formed amyloid-β peptide fibrils that may be involved in Alzheimer’s disease. These fibrils or similar onesform aggregates called “senile plaques” in the brains of patients with the memory- and identity-loss disease.

The fibrils the teams studied are made of a 42-amino-acid peptide, Aβ-42, which is one of two major forms of amyloid-β peptide. It is more neurotoxic, aggregates faster, and is more predominant in senile plaques than the other type, Aβ-40. Scientists have structurally analyzed Aβ-40 fibrils before. But structural analysis of full Aβ-42 fibrils—thought to be the main bad actors in Alzheimer’s disease and therefore the more important of the two types—has been elusive. Rest