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Biology subjects

Brown, M. J.

Publications and source records attributed to Brown, M. J..

6 recordsLinked to original sources

Big angiosperm genera are priorities for conservation

Species in big angiosperm genera ([≥]500 species) are often considered to be less well-known than those in smaller genera. Consequently, species in big genera are likely underrepresented in conservation at all levels, from analyses to actions. However, emerging evidence indicates that species in larger genera tend to have smaller geographic ranges (a strong correlate of increased extinction risk). Here, we test the generality of this pattern by quantifying the relationships between plant taxon size, extinction risk and climatic zone on a global scale. We find that species in larger genera are more likely to have small ranges, less likely to have a global Red List assessment, and, when assessed, are more likely to be threatened. Persistent obstacles to improving conservation documentation of big genera include taxonomic uncertainty, data shortfalls and number of species involved, requiring continued collaboration between taxonomy and conservation to reduce this bias and enable effective conservation of the quarter of plant species that big genera encompass. Article Impact StatementSpecies in big angiosperm genera are under-studied, under-assessed, and their extinction risk has been underestimated.

ecology↗

Genome size is positively correlated with extinction risk in herbaceous angiosperms

O_LIAngiosperms with large genomes experience nuclear-, cellular- and organism-level constraints that may limit their phenotypic plasticity and ecological niche. These constraints have been documented to vary across lineages, life-history strategies, ecogeographic patterns and environmental conditions. Therefore, we test the hypotheses that extinction risk is higher in large-genomed compared to small-genomed species, and that the effect of genome size varies across three selected covariates: life form, endemism, and climatic zones. C_LIO_LIWe collated genome size and extinction risk information for a representative sample of angiosperms comprising 3,250 species, which we analyzed alongside life form, endemism and climate variables using a phylogenetic framework. C_LIO_LIAngiosperm genome size is positively correlated with extinction risk, a pattern driven by a signal in herbaceous but not woody species, regardless of climate and endemism. The influence of genome size is stronger in endemic herbaceous species, but is relatively homogenous across different climates. Beyond its indirect link via endemism and climate, genome size also influences extinction risk directly and significantly. C_LIO_LIGenome size may serve as a proxy for difficult-to-measure parameters associated with resilience and vulnerability in herbaceous angiosperms. Therefore, it merits further exploration as a useful biological attribute for understanding intrinsic extinction risk and augmenting plant conservation efforts. C_LI

plant biology↗

CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent

Lymphopenia is common in severe COVID-19 disease, yet the mechanisms are poorly understood. In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to recovered, mild disease (p<0.0001). In severe disease, immunodominant CD4+ T cell responses to Spike-1(S1) produced increased in vitro TNF-, but impaired proliferation and increased susceptibility to activation-induced cell death (AICD). CD4+TNF-+ T cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.744, P<0.0001). TNF- blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ proliferation and abrogated S1-AICD in severe COVID-19 patients (P<0.001). Single-cell RNAseq demonstrated downregulation of Type-1 cytokines and NF{kappa}B signaling in S1-stimulated CD4+ cells with infliximab treatment. Lung CD4+ T cells in severe COVID-19 were reduced and produced higher TNF- versus PBMC. Together, our findings show COVID-19-associated CD4+ lymphopenia and dysfunction is autocrine TNF-/TNFRI-dependent and therapies targeting TNF- may be beneficial in severe COVID-19. One Sentence SummaryAutocrine TNF-/TNFRI regulates CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease.

immunology↗

Reversal of visual feedback modulates somatosensory plasticity

Reversed visual feedback during unimanual training increases transfer of skills to the opposite untrained hand and modulates plasticity in motor areas of the brain. However, it is unclear if unimanual training with reversed visual feedback also affects somatosensory areas. Here we manipulated visual input during unimanual training using left-right optical reversing spectacles and tested whether unimanual training with reversed vision modulates somatosensory cortical excitability to facilitate motor performance. Thirty participants practiced a unimanual ball-rotation task using the right hand with either left-right reversed vision (incongruent visual and somatosensory feedback) or direct vision (congruent feedback) of the moving hand. We estimated cortical excitability in primary somatosensory cortex (S1) before and after unimanual training by measuring somatosensory evoked potentials (SEPs). This was done by electrically stimulating the median nerve in the wrist while participants rested, and recording potentials over both hemispheres using electroencephalography. Performance of the ball-rotation task improved for both the right (trained) and left (untrained) hand after training across both direct and reversed vision conditions. Participants with direct vision of the right hand during training showed SEPs amplitudes increased bilaterally. In contrast, participants in the reversed visual condition showed attenuated SEPs following training. The results suggest that cortical suppression of S1 activity supports skilled motor performance after unimanual training with reversed vision, presumably by sensory gating of afferent signals from the movement. This finding provides insight into the mechanisms by which visual input interacts with the sensorimotor system and induces neuroplastic changes in S1 to support skilled motor performance.

neuroscience↗

Assembly of novel, nuclear dimers of the PI3-Kinase regulatory subunits underpins the pro-proliferative activity of the Cdc42-activated tyrosine kinase, ACK

The tyrosine kinase ACK is an oncogene associated with poor prognosis in human cancers. ACK promotes proliferation, in part, by contributing to the activation of Akt, the major PI3-Kinase effector. We show that ACK also regulates PI3-Kinase directly, via interactions with the PI3-Kinase regulatory subunits. ACK interacts with all five regulatory subunit isoforms and directly phosphorylates p85, p85{beta}, p55 and p50 on Tyr607 (or equivalent). Phosphorylation of p85{beta} at this residue promotes cell proliferation but, counterintuitively, ACK does not stimulate PI3-Kinase catalytic activity. We show that ACK stabilizes p85 levels by promoting an interaction between the p85 nSH2 domain and pTyr607, protecting p85 from ubiquitination. We demonstrate that ACK interacts with p85 exclusively in nuclear-enriched cell fractions where the increased levels of the regulatory subunits, together with the nSH2-pTyr607 interaction, promote formation of dimeric p85. We postulate that these novel dimers undertake nuclear functions that contribute to Cdc42-ACK driven oncogenesis. We propose that ACK shapes PI3-Kinase signalling by dampening the PIP3 response, whilst continuing to drive cell proliferation through Akt activation and hereto unexplored but crucial functions of nuclear dimeric p85. These new regulatory subunit dimers represent a previously undescribed mode of regulation for PI3-Kinase and potentially reveal additional avenues for therapeutic intervention.

molecular biology↗

Destructive Disinfection Of Infected Brood Prevents Systemic Disease Spread In Ant Colonies

Social insects protect their colonies from infectious disease through collective defences that result in social immunity. In ants, workers first try to prevent infection of colony members. Here, we show that if this fails and a pathogen establishes an infection, ants employ an efficient multicomponent behaviour - \"destructive disinfection\" - to prevent further spread of disease through the colony. Ants specifically target infected pupae during the pathogens non-contagious incubation period, relying on chemical sickness cues emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a body that specifically targets and eliminates infected cells, this social immunity measure sacrifices infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, the same principles of disease defence apply at different levels of biological organisation.

evolutionary biology↗