The progene hypothesis: the nucleoprotein world and how life began

ABSTRACT: In this article, I review the results of studies on the origin of life distinct from the popular RNA world hypothesis. The alternate scenario postulates the origin of the first bimolecular genetic system (a polynucleotide gene and a polypeptide processive polymerase) with simultaneous replication and translation and includes the following key features: 1. The bimolecular genetic system emerges not from mononucleotides and monoamino acids, but from progenes, namely, trinucleotides aminoacylated on 3′–end by a non-random amino acid (NpNpNp ~ pX ~ Aa, where N—deoxyribo- or ribonucleoside, p—phosphate, X—a bifunctional agent, for example ribose, Aa—amino acid, ~ macroerge bond). Progenes are used as substrates for simultaneous synthesis of a polynucleotide and a polypeptide. Growth of the system is controlled by the growing polypeptide, and the bimolecular genetic system emerges as an extremely rare event. The first living being (virus-like organism protoviroid, Protoviroidum primum) arises and reproduces in prebiotic liposome-like structures using progenes. A population of protoviroids possessing the genetic system evolves in accordance with the Darwinian principle. Early evolution from protoviroid world to protocell world is shortly described. 2. The progene forming mechanism (NpNp + Np ~ pX ~ Aa) makes it possible to explain the emergence of the prebiotic physicochemical group genetic code, as well as the selection of organic compounds for the future genetic system from the racemic environment. 3. The protoviroid is reproduced on a progene basis via replicative transcription-translation (RTT, the first molecular genetic process) that is similar to its modern counterparts. Nothing is required for the emergence and reproduction of the protoviroid except for progenes and conditions for their formation. 4. The general scheme of early evolution is as follows: prebiotic world → protoviroid (nucleoprotein) world → protocell (DNA-RNA-protein) world → LUCA (Last Universal Common Ancestor) → modern cell world. This scheme exclude the existence of an independent RNA world as predecessor of the cellular world. REVIEWERS: Dr. Thomas Dandekar, Dr. Bojan Zagrovic and Dr. Anthony Pool

Peptidergic control in a fruit crop pest: The spotted-wing drosophila, Drosophila suzukii

Neuropeptides play an important role in the regulation of feeding in insects and offer potential targets for the development of new chemicals to control insect pests. A pest that has attracted much recent attention is the highly invasive Drosophila suzukii, a polyphagous pest that can cause serious economic damage to soft fruits. Previously we showed by mass spectrometry the presence of the neuropeptide myosuppressin (TDVDHVFLRFamide) in the nerve bundle suggesting that this peptide is involved in regulating the function of the crop, which in adult dipteran insects has important roles in the processing of food, the storage of carbohydrates and the movement of food into the midgut for digestion. In the present study antibodies that recognise the C-terminal RFamide epitope of myosuppressin stain axons in the crop nerve bundle and reveal peptidergic fibres covering the surface of the crop. We also show using an in vitro bioassay that the neuropeptide is a potent inhibitor (EC50 of 2.3 nM) of crop contractions and that this inhibition is mimicked by the non-peptide myosuppressin agonist, benzethonium chloride (Bztc). Myosuppressin also inhibited the peristaltic contractions of the adult midgut, but was a much weaker agonist (EC50 = 5.7 μM). The oral administration of Bztc (5 mM) in a sucrose diet to adult female D. suzukii over 4 hours resulted in less feeding and longer exposure to dietary Bztc led to early mortality. We therefore suggest that myosuppressin and its cognate receptors are potential targets for disrupting feeding behaviour of adult D. suzukii

Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

PosterAutism spectrum disorder (ASD) is characterized by impairments in social communication and abnormal repetitive behavior patterns. Recent studies have shown a strong association between ASD and gastrointestinal (GI) symptomatology. Some individuals with ASD show altered reactivity to stress, as well as altered immune markers, particularly stress responsive cytokines including TNF-alpha and IL-6. To assess potential relationships between GI symptoms and stress response, we examined whether GI symptoms are associated with increases in stress-associated endocrine markers and cytokines in ASD. We also conducted exploratory analyses the examine the relationship between IL-6, TNF-alpha, cortisol, and intelligence, as well as the effects of the presence or absence of co-occurring medical conditions on the relationship between IL-6, TNF-alpha, cortisol, and GI symptoms. Given the aforementioned findings, we expected to find positive relationships between GI symptoms and biomarkers of stress, including cortisol levels, IL-6, and TNF-alpha

Associations between nutrient intake and gastrointestinal symptoms in autism spectrum disorder

Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is not well understood. Studies have shown conflicting evidence on whether there are nutritional deficiencies in the various diets of individuals with ASD. However, little is known about the relationship between dietary intake and GI symptomatology in ASD. The goal of the present study was to assess for potential relationships between GI symptoms and nutrient intake from diet in the same sample of individuals from the previous study, and to determine whether dietary differences might have contributed to our previously observed findings of a relationship between stress responses and GI functioning in ASD

Inhibition of Influenza M2-Induced Cell Death Alleviates Its Negative Contribution to Vaccination Efficiency

The effectiveness of recombinant vaccines encoding full-length M2 protein of influenza virus or its ectodomain (M2e) have previously been tested in a number of models with varying degrees of success. Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we demonstrated a decrease in protection when M2 was added to a DNA vaccination regimen that included influenza NP. Furthermore, we have constructed several fusion proteins of conserved genes of influenza virus and tested their expression in vitro and protective potential in vivo. The four-partite NP-M1-M2-NS1 fusion antigen that has M2 sequence engineered in the middle part of the composite protein was shown to not be cytotoxic in vitro. A three-partite fusion protein (consisting of NP, M1 and NS1) was expressed much more efficiently than the four-partite protein. Both of these constructs provided statistically significant protection upon DNA vaccination, with construct NP-M1-M2-NS1 being the most effective. We conclude that incorporation of M2 into a vaccination regimen may be beneficial only when its apparent cytotoxicity-linked negative effects are neutralized. The possible significance of this data for influenza vaccination regimens and preparations is discussed

A sol-gel based silver nanoparticle/polytetrafluorethylene (AgNP/PTFE) coating with enhanced antibacterial and anti-corrosive properties

In this research, a silver nanoparticle/polytetrafluorethylene (AgNP/PTFE) coating for metallic implants was fabricated using a facile layer-by-layer coating method. PTFE nanoparticles were immobilized in a sol–gel matrix and dip-coated onto 316L stainless steel via a mussel-inspired approach followed by AgNP deposition. Benefiting from the synergistic effect of antibacterial AgNP and non-stick PTFE, the AgNP/PTFE coating exhibited superior antibiofilm activity against Escherichia coli WT F1693 and enhanced corrosion resistance. Compared with surfaces only coated with PTFE, the AgNP/PTFE coated surfaces were capable of sustained release of silver ions, inhibiting up to ~50% bacterial biomass accumulation after 7 days. To understand the anti-adhesion mechanism, both classic DLVO and XDLVO theories were used to model and explain bacterial adhesion. Despite concerns that an over-release of silver ions may cause toxic effects towards mammalian cells, the coating procedures offered ease of control over the silver loading, making it potentially useful for preventing metallic implant-associated infections