Ion Gresser 1928-2019

Ion Gresser, a virologist who transformed understanding of the roles of interferons, may be best remembered for showing that in mice, interferon-α (IFN-α) can produce acute and chronic disease. At the time Gresser began these studies, interferon was considered to be a selective antiviral substance, harmless to uninfected cells and organisms, and there was no indication that cytokines would play a role in pathogenesis. That belief was shattered with the 1975 Nature publication with the simple title “Lethality of interferon preparations for newborn mice.” Gresser subsequently demonstrated that antibodies to IFN-α can protect young mice from death caused by infection with lymphocytic choriomeningitis virus. This study can be considered a stepping-stone for the therapeutic application of antibodies to cytokines in the treatment of human disease, which was introduced much later and revolutionized the management of some autoimmune diseases

Interferons: Success in anti-viral immunotherapy

The interferons (IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered as standard of care in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment for HCV infection in phase III clinical trials. However, though effective, using IFNs as a treatment is not without the need for caution. IFNs are such powerful cytokines that affect a wide array of cell types; as a result, patients usually experience unpleasant symptoms, with a percentage of patients suffering system wide effects. Thus, constant monitoring is required for patients treated with IFN in order to reach the treatment goals of suppressing virus infection and maintaining quality of life

Using PET imaging to track STING-induced interferon signaling

In the 19th century, Ilya Metchnikoff defined and broadened our initial understanding of phagocytosis and, in 1908, went on to show that a cellular component (i.e., DNA) stimulates immune responses (1). About a century later, Janeway conceptualized pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) (2). Since then, we know that PAMP recognition by innate immune cells via PRRs activates the production of several cytokines, including interferons (IFNs), with the eventual recruitment of lymphocytes. Subsequent research discovered that innate immune recognition of double-stranded DNA (dsDNA) triggers autoimmune diseases (3). However, before the discovery of dsDNA sensors, an endoplasmic reticulum (ER) protein encoded by the TMEM173 gene, known as a stimulator of IFN genes (STING), was identified as a significant factor involving DNA recognition in innate immunity (4). Subsequently, scientists discovered that the direct cytosolic DNA sensor (cGAS) activates the expression of type 1 IFNs (5). Today, it is well known that activation of cGAS-cGAMP-STING signaling is triggered by cytosolic DNA and is necessary for antimicrobial and antitumor immune responses. In PNAS, Liang et al. (6) describe an innovative process for monitoring STING-induced IFN signaling. Induction of IFN signaling by STING occurs on detection of cytoplasmic DNA, whichmay be tumor- or microbial-derived. STING is activated when cGAS catalyzes the synthesis of cyclic dinucleotides (CDNs) including 2′3′-cGAMP (7). STING is translocated from the ER to the perinucleus, phosphorylated by TANK-binding kinase 1 (TBK1) and recruits IFN regulatory factor 3 (IRF3), which in turn is phosphorylated by TBK1, forms a dimer, and enters the nucleus. Phosphorylated IRF3 activates transcription of type 1 IFNs and other relevant cytokines (8) which bind to the heterodimeric IFN receptors (IFNAR1 and IFNAR2) and recruits Janus family kinase 1(Jak1) and tyrosine kinase 2 (Tyk2), which in turn phosphorylates and activates IFNAR1 and IFNAR2. Activated IFNAR1 and 2 phosphorylate signal transducers and activators of transcription (STAT) proteins (STAT1 and STAT2), which are transferred to the nucleus along with IFN regulatory factor 9 (IRF9), to enhance transcription of IFN target genes (9) and subsequently activate the innate and adaptive immune responses

Experimental evidence for the molecular molybdenum fluorides MoF to MoF6: a matrix isolation and DFT investigation

All of the molecular molybdenum fluorides, MoF to MoF6, have been synthesised from the reaction of thermally evaporated molybdenum atoms with fluorine molecules and atoms, trapped in argon matrices, and characterised by matrix isolation IR spectroscopy in conjunction with DFT calculations. This includes the first spectroscopic characterisation of MoF and MoF2, the latter of which is very bent with a bond angle of ca. 133°, the reassignment of the IR spectral data for trigonal planar MoF3, the observation of tetrahedral MoF4, the assignment of new features to MoF5 which displays a Jahn-Teller distorted trigonal bipyramidal structure, and octahedral MoF6. When the reaction of fluorine molecules and heated molybdenum is allowed to take place, MoF6, MoF4 and (MoF5)3 are observed

"If chemists don’t do it, who is going to?" Peer-driven occupational change and the emergence of green chemistry

Occupational membership guides what people do, how they think of themselves, and how they interact in organizations and with society. While a rich literature explains how occupations adapt in response to external triggers for change, we have limited insight into how occupational incumbents, absent external triggers, work to influence how their peers do their work. We investigate the emergence and growth of “green chemistry,” an effort by chemists to encourage other chemists to reduce the health, safety, and environmental impacts of chemical products and processes. We find that advocates simultaneously advanced normalizing, moralizing, and pragmatizing frames for green chemistry and that each frame resonated differently with chemists in their various occupational roles. While this pluralistic approach generated broad acceptance of the change effort, it also exposed tensions, which threatened the coherence of the change. Divergent responses of advocates to these tensions contribute to a persistent state of pluralism and dynamism in the change effort. We discuss implications for theory on occupational change arising from our attention to internally-generated peer-driven change, heterogeneity within occupations, and change efforts that moralize occupational work.Meyer Fund for Sustainability grant (University of Oregon

Perceptual training to increase drivers' ability to spot motorcycles at T-junctions

Motorcyclists too often collide with other road users who pull out of side roads in front of them. These other road users typically report making all the necessary visual checks, despite failing to see the approaching motorcycle. These Look But Fail To See errors appear to be attenuated in road users who themselves have motorcycling experience, suggesting that motorcycle exposure may lower thresholds for spotting these vulnerable road users through natural perceptual learning. This raises the possibility that perceptual training could improve car drivers' abilities to spot motorcycles. Two experiments are reported. The first experiment demonstrated that a T-junction task, requiring participants to detect an approaching vehicle in briefly displayed images, was sensitive to participants' motorcycle experience, with dual drivers (who both ride motorcycles and drive cars) performing better than average car drivers. Following this, a second experiment split the car drivers into 2 groups. One group undertook a Pelmanism task requiring participants to match pairs of motorcycles, while the control group had to match pairs of fruit. When the two groups were re-tested on the T-junction task, the group who had undergone perceptual training for motorcycles via the Pelmanism task, were better able to identify approaching motorcycles, but not approaching cars. The results suggest that gamification of perceptual training for motorcycle detection provides a novel opportunity to improve driver safety