Evolution of complexity in the zebrafish synapse proteome

The proteome of human brain synapses is highly complex and mutated in over 130 diseases. This complexity arose from two whole genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases, however its synapse proteome is uncharacterised and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown. We report the characterisation of the proteomes and ultrastructure of central synapses in zebrafish and analyse the importance of the TSGD. While the TSGD increases overall synapse proteome complexity, the Post Synaptic Density (PSD) proteome of zebrafish has lower complexity than mammals. A highly conserved set of ~1000 proteins is shared across vertebrates. PSD ultrastructural features are also conserved. Lineage-specific proteome differences indicate vertebrate species evolved distinct synapse types and functions. The datasets are a resource for a wide range of studies and have important implications for the use of zebrafish in modelling human synaptic diseases

HelmCoP: An Online Resource for Helminth Functional Genomics and Drug and Vaccine Targets Prioritization

A vast majority of the burden from neglected tropical diseases result from helminth infections (nematodes and platyhelminthes). Parasitic helminthes infect over 2 billion, exerting a high collective burden that rivals high-mortality conditions such as AIDS or malaria, and cause devastation to crops and livestock. The challenges to improve control of parasitic helminth infections are multi-fold and no single category of approaches will meet them all. New information such as helminth genomics, functional genomics and proteomics coupled with innovative bioinformatic approaches provide fundamental molecular information about these parasites, accelerating both basic research as well as development of effective diagnostics, vaccines and new drugs. To facilitate such studies we have developed an online resource, HelmCoP (Helminth Control and Prevention), built by integrating functional, structural and comparative genomic data from plant, animal and human helminthes, to enable researchers to develop strategies for drug, vaccine and pesticide prioritization, while also providing a useful comparative genomics platform. HelmCoP encompasses genomic data from several hosts, including model organisms, along with a comprehensive suite of structural and functional annotations, to assist in comparative analyses and to study host-parasite interactions. The HelmCoP interface, with a sophisticated query engine as a backbone, allows users to search for multi-factorial combinations of properties and serves readily accessible information that will assist in the identification of various genes of interest. HelmCoP is publicly available at: http://www.nematode.net/helmcop.html

Comparative genomics of the major parasitic worms

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms

Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

There is a long-standing paradox that N-methyl-D-aspartate receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington’s disease and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling

Spatial variation and inconsistency between estimates of onset of muscle activation from EMG and ultrasound.

Delayed onset of muscle activation can be a descriptor of impaired motor control. Activation onset can be estimated from electromyography (EMG)-registered muscle excitation and from ultrasound-registered muscle motion, which enables non-invasive measurements in deep muscles. However, in voluntary activation, EMG- and ultrasound-detected activation onsets may not correspond. To evaluate this, ten healthy men performed isometric elbow flexion at 20% to 70% of their maximal force. Utilising a multi-channel electrode transparent to ultrasound, EMG and M(otion)-mode ultrasound were recorded simultaneously over the biceps brachii muscle. The time intervals between automated and visually estimated activation onsets were correlated with the regional variation of EMG and muscle motion onset, contraction level and speed. Automated and visual onsets indicated variable time intervals between EMG- and motion onset, median (interquartile range) 96 (121) ms and 48 (72) ms, respectively. In 17% (computed analysis) or 23% (visual analysis) of trials, motion onset was detected before local EMG onset. Multi-channel EMG and M-mode ultrasound revealed regional differences in activation onset, which decreased with higher contraction speed (Spearman ??=?0.45, P?<?0.001). In voluntary activation the heterogeneous motor unit recruitment together with immediate motion transmission may explain the high variation of the time intervals between local EMG- and ultrasound-detected activation onset

The physical activity at work (PAW) study: a cluster randomised trial of a multicomponent short-break intervention to reduce sitting time and increase physical activity among office workers in Thailand

10.1016/j.lansea.2022.100086The Lancet Regional Health - Southeast Asia8100086-10008

EU agricultural reform fails on biodiversity

In December 2013, the European Union (EU) enacted the reformed Common Agricultural Policy (CAP) for 2014–2020, allocating almost 40% of the EU's budget and influencing management of half of its terrestrial area. Many EU politicians are announcing the new CAP as “greener,” but the new environmental prescriptions are so diluted that they are unlikely to benefit biodiversity. Individual Member States (MSs), however, can still use flexibility granted by the new CAP to design national plans to protect farmland habitats and species and to ensure long-term provision of ecosystem services