Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic Drosophila Clock Mutant ClkJrk

An organism's biological day is characterized by a pattern of anticipatory physiological and behavioral changes that are governed by circadian clocks to align with the 24-h cycling environment. Here, we used flash electroretinograms (ERGs) and steady-state visually evoked potentials (SSVEPs) to examine how visual responsiveness in wild-type Drosophila melanogaster and the circadian clock mutant ClkJrk varies over circadian time. We show that the ERG parameters of wild-type flies vary over the circadian day, with a higher luminance response during the subjective night. The SSVEP response that assesses contrast sensitivity also showed a time-of-day dependence, including 2 prominent peaks within a 24-h period and a maximal response at the end of the subjective day, indicating a tradeoff between luminance and contrast sensitivity. Moreover, the behaviorally arrhythmic ClkJrk mutants maintained a circadian profile in both luminance and contrast sensitivity, but unlike the wild-types, which show bimodal profiles in their visual response, ClkJrk flies show a weakening of the bimodal character, with visual responsiveness tending to peak once a day. We conclude that the ClkJrk mutation mainly affects 1 of 2 functionally coupled oscillators and that the visual system is partially separated from the locomotor circadian circuits that drive bouts of morning and evening activity. As light exposure is a major mechanism for entrainment, our work suggests that a detailed temporal analysis of electrophysiological responses is warranted to better identify the time window at which circadian rhythms are most receptive to light-induced phase shifting

Functional diversity of mesograzers in an eelgrass-epiphyte system

Historically, small invertebrate grazers in marine plant communities have been considered to be a relatively homogeneous group in their impact on ecosystem processes. However, recent studies propose that species composition is an important agent in determining grazer effects. We used four mesocosm experiments to test the biomass-specific and density-dependent effects of common mesograzers in temperate regions (Littorina littorea, Rissoa membranacea, Idotea baltica and Gammarus oceanicus) on epiphyte and eelgrass biomass and productivity. Mesograzer species identity strongly influenced epiphyte accumulation and eelgrass growth, where Rissoa was the most efficient mesograzer (per biomass) and Gammarus had the weakest impact. Density-dependent effects varied considerably among species. Both gastropod species reduced epiphyte accumulation in direct proportion to their density, and Littorina had the strongest negative effect on epiphyte biomass. The impact of Idotea seemed to level off to a threshold value and Gammarus had no density-dependent effect on epiphyte accumulation at all. Rissoa and Idotea increased eelgrass productivity in accordance with their effect on epiphyte accumulation, whereas Littorina showed a less positive effect than could be expected by its strong impact on epiphyte biomass. Gammarus had no significant impact on eelgrass growth. Our results show that the different functional traits of superficially similar mesograzers can have important consequences for ecosystem processes in macrophyte systems

Reef fishes at all trophic levels respond positively to effective marine protected areas

Marine Protected Areas (MPAs) offer a unique opportunity to test the assumption that fishing pressure affects some trophic groups more than others. Removal of larger predators through fishing is often suggested to have positive flow-on effects for some lower trophic groups, in which case protection from fishing should result in suppression of lower trophic groups as predator populations recover. We tested this by assessing differences in the trophic structure of reef fish communities associated with 79 MPAs and open-access sites worldwide, using a standardised quantitative dataset on reef fish community structure. The biomass of all major trophic groups (higher carnivores, benthic carnivores, planktivores and herbivores) was significantly greater (by 40% - 200%) in effective no-take MPAs relative to fished open-access areas. This effect was most pronounced for individuals in large size classes, but with no size class of any trophic group showing signs of depressed biomass in MPAs, as predicted from higher predator abundance. Thus, greater biomass in effective MPAs implies that exploitation on shallow rocky and coral reefs negatively affects biomass of all fish trophic groups and size classes. These direct effects of fishing on trophic structure appear stronger than any top down effects on lower trophic levels that would be imposed by intact predator populations. We propose that exploitation affects fish assemblages at all trophic levels, and that local ecosystem function is generally modified by fishing

Propylene glycol inactivates respiratory viruses and prevents airborne transmission

Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, vaporised PG efficiently abolishes influenza A virus and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels well below those tolerated by mammals. We present PG vapour as a first-in-class non-toxic airborne virucide that can prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health

Acute Drug Treatment in the Early C. elegans Embryo

Genetic and genome-wide RNAi approaches available in C. elegans, combined with tools for visualizing subcellular events with high-resolution, have led to increasing adoption of the early C. elegans embryo as a model for mechanistic and functional genomic analysis of cellular processes. However, a limitation of this system has been the impermeability of the embryo eggshell, which has prevented the routine use of small molecule inhibitors. Here, we present a method to permeabilize and immobilize embryos for acute inhibitor treatment in conjunction with live imaging. To identify a means to permeabilize the eggshell, we used a dye uptake assay to screen a set of 310 candidate genes defined by a combination of bioinformatic criteria. This screen identified 20 genes whose inhibition resulted in >75% eggshell permeability, and 3 that permeabilized embryos with minimal deleterious effects on embryo production and early embryonic development. To mount permeabilized embryos for acute drug addition in conjunction with live imaging, we combined optimized inhibition of one of these genes with the use of a microfabricated chamber that we designed. We demonstrate that these two developments enable the temporally controlled introduction of inhibitors for mechanistic studies. This method should also open new avenues of investigation by allowing profiling and specificity-testing of inhibitors through comparison with genome-wide phenotypic datasets

A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

MSACompro: protein multiple sequence alignment using predicted secondary structure, solvent accessibility, and residue-residue contacts

<p>Abstract</p> <p>Background</p> <p>Multiple Sequence Alignment (MSA) is a basic tool for bioinformatics research and analysis. It has been used essentially in almost all bioinformatics tasks such as protein structure modeling, gene and protein function prediction, DNA motif recognition, and phylogenetic analysis. Therefore, improving the accuracy of multiple sequence alignment is important for advancing many bioinformatics fields.</p> <p>Results</p> <p>We designed and developed a new method, MSACompro, to synergistically incorporate predicted secondary structure, relative solvent accessibility, and residue-residue contact information into the currently most accurate posterior probability-based MSA methods to improve the accuracy of multiple sequence alignments. The method is different from the multiple sequence alignment methods (e.g. 3D-Coffee) that use the tertiary structure information of some sequences since the structural information of our method is fully predicted from sequences. To the best of our knowledge, applying predicted relative solvent accessibility and contact map to multiple sequence alignment is novel. The rigorous benchmarking of our method to the standard benchmarks (i.e. BAliBASE, SABmark and OXBENCH) clearly demonstrated that incorporating predicted protein structural information improves the multiple sequence alignment accuracy over the leading multiple protein sequence alignment tools without using this information, such as MSAProbs, ProbCons, Probalign, T-coffee, MAFFT and MUSCLE. And the performance of the method is comparable to the state-of-the-art method PROMALS of using structural features and additional homologous sequences by slightly lower scores.</p> <p>Conclusion</p> <p>MSACompro is an efficient and reliable multiple protein sequence alignment tool that can effectively incorporate predicted protein structural information into multiple sequence alignment. The software is available at <url>http://sysbio.rnet.missouri.edu/multicom_toolbox/</url>.</p

Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis

Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H+ export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin