Biasing the perception of ambiguous vocal affect: a TMS study on frontal asymmetry

Several sources of evidence point toward a link between asymmetry of prefrontal brain activity and approach–withdrawal tendencies. Here, we tested the causal nature of this link and examined if the categorization of an ambiguous approach- or withdrawal-related vocal signal can be biased by manipulating left and right frontal neural activity. We used voice morphing of affective non-verbal vocalizations to create individually tailored affectively ambiguous stimuli on an Anger–Fear continuum—two emotions that represent extremes on the approach–withdrawal dimension. We tested perception of these stimuli after 10 min of low-frequency repetitive transcranial magnetic stimulation over left or right dorsolateral prefrontal cortex or over the vertex (control), a technique that has transient inhibitory effects on the targeted brain region. As expected, ambiguous stimuli were more likely perceived as expressing Anger (approach) than Fear (withdrawal) after right prefrontal compared with left prefrontal or control stimulation. These results provide the first evidence that the manipulation of asymmetrical activity in prefrontal cortex can change the explicit categorization of ambiguous emotional signals

High MMP-9 Expression May Contribute to Retroprosthetic Membrane Formation after KPro Implantation in Rabbit Corneal Alkali Burn Model

Purpose. To evaluate aqueous humor MMP-9 levels in alkali-burned rabbit cornea following KPr implantation and their roles in RPMs formation. Methods. Left eyes of 36 rabbits received a deep corneal alkali wound. 12 corneas were implanted with KPro and the other 24 control corneas were either penetrating keratoplasty or left without keratoplasty. Aqueous humor MMP-9 and TIMP-1 levels were determined and RPMs were obtained for histopathological and ultrastructural examination. Results. Alkali exposure induced significant increase in aqueous humor MMP-9 level and the data were further enhanced by KPro implantation. By contrast, TMIP-1 levels in aqueous humor showed a decreased trend following corneal alkali burn and KPro surgery. RPMs were developed in 5 out of 10 cases of KPro successfully implanted eyes. Histopathology showed the presence of a large number of fibroblasts and collagen fibers arranged irregularly with inflammatory cells infiltration, and an ingrowth of new blood vessels in this retrokeratoprosthesis fibrous tissue. Immunohistochemical analysis showed positive stain of RPMs for both MMP-9 and TIMP-1. Aqueous humor MMP-9 levels were significantly higher in RPM group postoperatively, while TIMP-1 levels were comparatively lower than that of No-RPM group. Conclusions. Our study evidenced the potential pathophysiological role of MMP-9 expression in RPM formation following KPro implantation

Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

Addiction is regarded as a disorder of inflexible choice with behavior dominated by immediate positive rewards over longer-term negative outcomes. However, the psychological mechanisms underlying the effects of self-administered drugs on behavioral flexibility are not well understood. To investigate whether drug exposure causes asymmetric effects on positive and negative outcomes we used a reversal learning procedure to assess how reward contingencies are utilized to guide behavior in rats previously exposed to intravenous cocaine self-administration (SA). Twenty-four rats were screened for anxiety in an open field prior to acquisition of cocaine SA over six daily sessions with subsequent long-access cocaine SA for 7 days. Control rats (n = 24) were trained to lever-press for food under a yoked schedule of reinforcement. Higher rates of cocaine SA were predicted by increased anxiety and preceded impaired reversal learning, expressed by a decrease in lose-shift as opposed to win-stay probability. A model-free reinforcement learning algorithm revealed that rats with high, but not low cocaine escalation failed to exploit previous reward learning and were more likely to repeat the same response as the previous trial. Eight-day withdrawal from high cocaine escalation was associated, respectively, with increased and decreased dopamine receptor D2 (DRD2) and serotonin receptor 2C (HTR2C) expression in the ventral striatum compared with controls. Dopamine receptor D1 (DRD1) expression was also significantly reduced in the orbitofrontal cortex of high cocaine-escalating rats. These findings indicate that withdrawal from escalated cocaine SA disrupts how negative feedback is used to guide goal-directed behavior for natural reinforcers and that trait anxiety may be a latent variable underlying this interaction.Pinsent Darwin Studentship, Cambridge University Swedish Research Council AXA Research Fund National Health and MRC of Australia Cambridge Isaac Newton Trust Boehringer Ingelheim Pharma GmbH, German

Correction: Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone

OBJECTIVE: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. DESIGN: Randomized, masked multicenter study. PARTICIPANTS: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. METHODS: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). MAIN OUTCOME: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. RESULTS: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy ( CONCLUSIONS: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article

Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON; outputs from 2023 meeting)

Rapports Scientifiques du CIEM. Volume 6, nº 12The Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON) was set up to provide ICES and stakeholders with a summary of knowledge on the role of fishing in the process of carbon budgets, sequestration and footprint in the ocean. The workshop addressed the potential impact of fishing on the biological carbon pump (BCP), the possible impacts of bottom trawling on carbon stores in the seabed, as well as considering emissions from fishing vessels. The overall aim was to generate proposals on how to develop an ICES approach to fishing and its role in the ocean carbon budget, and to develop a roadmap for a way forward. The main findings were that knowledge of the BCP in the open ocean was reasonably well developed, but that key gaps existed. In particular, information on the biomass of mesopelagic fish and other biota, and of some of the key processes e.g. fluxes and fish bioenergetics. Knowledge is much weaker for the BCP in shelf seas, where the bulk of fishing occurs. In particular, while biomass of fish was often well quantified, unlike the open ocean, the understanding of the important processes was lacking, particularly for the fate of faecal pellets and deadfall at the seabed. There is extensive scientific knowledge of the impact of fishing on the seabed, but what is un-clear is what it means for seabed carbon storage. There have been numbers of studies, which give a very divided view on this. There has also been open controversy about this in the literature. Physical disturbance to the seabed from fishing can affect sediment transport and has the potential to facilitate remineralization, but precise impacts will depend on habitat, fishing métier, and other environmental factors. From this, it is clear that more research is needed to resolve the controversy, and to quantify the impacts from different fishing gears and on different substrates or habitats in terms of carbon storage. There has been much more research on minimizing fuel use by fishing vessels, and hence emissions, but this has mainly focused on fuel efficiency, fuel use per unit of landed catch, and less on the total emissions. Baselines for fuel use are available at the global level, but are lacking at the national and vessel level. There is a need for standardization of methodologies and protocols, and for improving the uptake of fuel conservation measures by industry, as well as for improving the uptake of existing and potential fuel conservation and efficiency measures by industry. Finally, a roadmap was proposed to develop research and synthesis, on the understandings of the processes involved, the metrics and how to translate this into possible advice for policy-makers. To that end, a further workshop was proposed in 2024.info:eu-repo/semantics/publishedVersio

Structural Insights into Viral Determinants of Nematode Mediated Grapevine fanleaf virus Transmission

Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV), a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP), carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD) poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp) in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector

A Family of Plasmodesmal Proteins with Receptor-Like Properties for Plant Viral Movement Proteins

Plasmodesmata (PD) are essential but poorly understood structures in plant cell walls that provide symplastic continuity and intercellular communication pathways between adjacent cells and thus play fundamental roles in development and pathogenesis. Viruses encode movement proteins (MPs) that modify these tightly regulated pores to facilitate their spread from cell to cell. The most striking of these modifications is observed for groups of viruses whose MPs form tubules that assemble in PDs and through which virions are transported to neighbouring cells. The nature of the molecular interactions between viral MPs and PD components and their role in viral movement has remained essentially unknown. Here, we show that the family of PD-located proteins (PDLPs) promotes the movement of viruses that use tubule-guided movement by interacting redundantly with tubule-forming MPs within PDs. Genetic disruption of this interaction leads to reduced tubule formation, delayed infection and attenuated symptoms. Our results implicate PDLPs as PD proteins with receptor-like properties involved the assembly of viral MPs into tubules to promote viral movement

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations:Experience from the MJFF Global Genetic Parkinson's Disease Project

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.</p