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Biology subjects

Simpson, N.

Publications and source records attributed to Simpson, N..

6 recordsLinked to original sources

Gravitational expectations simultaneously attract and repel perception

Perception is typically biased towards prior expectations. In some cases, however, it seems repelled away from expectations, such that percepts appear less like what is expected. Even more intriguingly, separate studies have recently reported that predictions derived from gravity may shape perception in opposing ways. Specifically, gravity causes unsupported objects to accelerate downwards, leading to two predictions; that objects will move downwards (location prior) and at an increasing speed (acceleration prior). There is evidence that perceptual judgements are attracted towards location priors yet repelled from acceleration ones. Here we examine these effects in the same paradigm to determine whether they result from different types of stimuli and judgement, or more interestingly, might result from opposite influences of common predictive mechanisms influencing perception. We first replicate previous reports of a systematic bias to report upward moving objects as more accelerating than downward moving objects: effectively a repulsion from acceleration priors. We then show that the effect applies both at the level of retinal space and due to contextual cues concerning gravitational direction. Finally, we find that participants errors in a location reproduction task are similarly consistent with a repulsion from acceleration priors and, simultaneously, with an attraction towards location priors. We conclude by considering the ways in which these concurrent attractive and repulsive biases may reflect mechanisms optimising fast, accurate, and informative experiences in our ever-changing sensory world, therefore optimising the interface between perception and learning. Public Significance StatementIn a series of behavioural experiments, we show that expectations about how objects move due to gravity concurrently attract perception towards the prediction that objects move downwards, and repel perception away from the prediction that they do so at an increasing rate. These opposing influences inform current theories of perceptual processing, which explain how expectations may generate percepts that are fast, veridical, and informative.

neuroscience↗

An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.

Recurrent implantation failure (RIF) is defined after three or more good quality embryo transfers following in vitro fertilisation without a successful pregnancy outcome. Many factors contribute to RIF however, the endometrial contribution remains unclear. Previous work by our group has identified a micro-RNA (miRNA) miR-185-5p as conserved across placental mammal irrespective of implantation strategies. We tested the hypothesis that miR-185-5p and the pathways it regulates, may be disrupted in the endometria of women with RIF. A human endometrial epithelial cells line (Ishikawa cells) was transfected with mimics or inhibitors for miR-185-5p for 24 (for implantation assay) or 48 hr (for proteomic analysis) along with non-targeting controls. There was a significant different in percentage attachment of BeWoW spheroids to cells transfected with miR-185-5p mimic compared to inhibitor (P<0.05). Transfection of epithelial cells with miR-185-5p altered expression of 1450 (mimic alone) and 509 (inhibitor alone) proteins respective of which, 146 were modified by both. Comparison of predicted targets of miR-185-5p, proteins modified by this study, and key endometrial genes from the literature determined genes and proteins associated with CNP family were further investigated in biopsies from individuals with (n=10) and without RIF (n=9) with CSNK1D expression significantly lower (p<0.05) in individuals with RIF. Collectively these data demonstrate that miR-185-5p modifies pathways that are important for successful implantation in humans.

cell biology↗

Extinction risk, reconstructed catches, and management of chondrichthyan fishes in the Western Central Atlantic Ocean

Chondrichthyan fishes are among the most threatened vertebrates on the planet because many species have slow life histories that are outpaced by intense fishing. The Western Central Atlantic Ocean, which includes the greater Caribbean, is a hotspot of chondrichthyan biodiversity and abundance, but is historically characterized by extensive shark and ray fisheries and a lack of sufficient data for effective management and conservation. To inform future research and management decisions, we analyzed patterns in chondrichthyan extinction risk, reconstructed catches, and regulations in this region. We summarized the extinction risk of 180 sharks, rays, and chimaeras using contemporary IUCN Red List assessments and found that over one-third (35.6%) were assessed as Vulnerable, Endangered, or Critically Endangered largely due to fishing. Reconstructed catches from 1950 to 2016 reached their peak in 1992, then declined by 40.2% through the end of the series. The United States, Venezuela, and Mexico were responsible for most catches and hosted large proportions of the regional distributions of threatened species; these countries therefore held the greatest responsibility for chondrichthyan management. The abundance and resolution of fisheries landings data were poor in much of the region, and national-level regulations varied widely across jurisdictions. Deepwater fisheries represent an emerging threat, although many deepwater chondrichthyans currently find refuge beyond the depths of most fisheries. Regional collaboration as well as effective and enforceable management informed by more complete fisheries data, particularly from small-scale fisheries, are required to protect and recover threatened species and ensure sustainable fisheries.

ecology↗

Rational Designed Hybrid Peptides Show up to a 6-fold Increase in Antimicrobial Activity and Demonstrate Different Ultrastructural Changes as the Parental Peptides measured by BioSAXS

Antimicrobial peptides (AMPs) are a promising class of compounds being developed against multi-drug resistant bacteria. Hybridization has been reported to increase antimicrobial activity. Here, two proline-rich peptides (consP1: VRKPPYLPRPRPRPL-CONH2 and Bac5-v291: RWRRPIRRRPIRPPFWR-CONH2) were combined with two arginine-isoleucine-rich peptides (optP1: KIILRIRWR-CONH2 and optP7: KRRVRWIIW-CONH2). Proline-rich antimicrobial peptides (PrAMPs) are known to inhibit the bacterial ribosome, shown also for Bac5-v291, whereas it is hypothesized a "dirty drug" model for the arginine-isoleucine-rich peptides. That hypothesis was underpinned by transmission electron microscopy and biological small-angle X-ray scattering (BioSAXS). The hybrid peptides showed a stronger antimicrobial activity compared to the proline-rich peptides, except when compared to Bac5-v291 against E. coli. The increase in activity compared to the arginine-isoleucine-rich peptides was up to 6-fold, however, it was not a general increase but was dependent on the combination of peptides and bacteria. BioSAXS experiments revealed that proline-rich peptides and arginine-isoleucine-rich peptides induce very different ultrastructural changes in E. coli, whereas a hybrid peptide (hyP7B5GK) shows changes, different to both parental peptides and the untreated control. These different ultrastructural changes indicated that the mode of action of the parental peptides is different from each other as well as from the hybrid peptide hyP7B5GK. All peptides showed very low haemolytic activity, some of them showed a 100-fold or larger therapeutic window, demonstrating the potential for further drug development.

microbiology↗

Immune profiling of cord blood after prolonged rupture of membranes.

We hypothesised that foetal immune responses to an infectious challenge may be detected by genome-wide transcriptional profiling of cord blood. In order to test this hypothesis, we sought to identify transcriptomic changes in post-natal cord blood samples following prolonged pre-labour rupture of membranes (PROM) as a surrogate for increased risk of infection. By comparison to controls we found increased levels of blood transcripts in a subset of prolonged PROM cases, significantly enriched for innate immune system signalling pathways. These changes were idiosyncratic, suggesting qualitative and quantitative variation in foetal immune responses which may reflect differences in exposure and/or in host genetics. Our data support the view that PROM represents an infection risk to the foetus. In addition, we propose that cord blood transcriptional profiling offers exciting opportunities to identify immune correlates of clinical outcome following potential in utero exposures to infection. These may be used to elucidate the mechanisms of immunological protection and pathology in the foetus and identify biomarkers to stratify the risk of adverse outcomes.

immunology↗

Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces both BDNF protein and gene expression. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both major depression and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. METHODS: BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC; BA24), caudal brainstem and rostral brainstem. The relationships between these measures and major depression, death by suicide and reported childhood adversity were examined. RESULTS: Depressed subjects had an excess of the Met allele and lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to early life adversity and/or died by suicide compared to nonsuicide decedents and no reported childhood adversity. CONCLUSIONS: This study provides further evidence for low BDNF in major depression related to the BDNF met risk allele. Future studies should seek to determine how altered BDNF expression contributes to MDD and suicide.

neuroscience↗