Comparative analysis of diversity based on morphoagronomic traits and molecular markers in durum wheat under heat stress

The objectives of this study were to compare the application and utility of sequence-related amplified polymorphism (SRAP) and target region amplification polymorphism (TRAP) techniques for the analysis of genetic diversity among durum wheat genotypes under heat stress and to compare genetic diversity estimated using molecular markers with morpho-agronomic performance under heat stress. Six durum wheat genotypes were used in this study. They were evaluated phenotypically for heat tolerance. The dendrogram generated from standardized morpho-agronomic data separated the six durum wheat genotypes into three main groups. The dendrogram generated from the standardized morpho-agronomic data separated the six durum wheat genotypes into three clusters, which diverged at similarity index of 0.72. The dendrogram based on SRAP markers differed from that based on TRAP markers. The combined dendrogram (SRAP, TRAP and morpho-agronomic data) agrees better with the grouping of these durum wheat genotypes depending on pedigree and the dendrogram generated by morpho-agronomic data alone.Key words: Durum wheat, genetic diversity, heat tolerance, morpho-agronomic, sequence-related amplified polymorphism (SRAP) markers, target region amplification polymorphism (TRAP) markers

Impairments in reinforcement learning do not explain enhanced habit formation in cocaine use disorder.

RATIONALE: Drug addiction has been suggested to develop through drug-induced changes in learning and memory processes. Whilst the initiation of drug use is typically goal-directed and hedonically motivated, over time, drug-taking may develop into a stimulus-driven habit, characterised by persistent use of the drug irrespective of the consequences. Converging lines of evidence suggest that stimulant drugs facilitate the transition of goal-directed into habitual drug-taking, but their contribution to goal-directed learning is less clear. Computational modelling may provide an elegant means for elucidating changes during instrumental learning that may explain enhanced habit formation. OBJECTIVES: We used formal reinforcement learning algorithms to deconstruct the process of appetitive instrumental learning and to explore potential associations between goal-directed and habitual actions in patients with cocaine use disorder (CUD). METHODS: We re-analysed appetitive instrumental learning data in 55 healthy control volunteers and 70 CUD patients by applying a reinforcement learning model within a hierarchical Bayesian framework. We used a regression model to determine the influence of learning parameters and variations in brain structure on subsequent habit formation. RESULTS: Poor instrumental learning performance in CUD patients was largely determined by difficulties with learning from feedback, as reflected by a significantly reduced learning rate. Subsequent formation of habitual response patterns was partly explained by group status and individual variation in reinforcement sensitivity. White matter integrity within goal-directed networks was only associated with performance parameters in controls but not in CUD patients. CONCLUSIONS: Our data indicate that impairments in reinforcement learning are insufficient to account for enhanced habitual responding in CUD.This research was funded by the Medical Research Council (MR/J012084/1) and the NIHR Cambridge Biomedical Research Centre and was conducted at the NIHR Cambridge Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was also supported in part by a Medical Research Council (MRC) Clinical Research Infrastructure award (MR/M009041/1). R.N.C. consults for Campden Instruments and receives royalties from Cambridge Enterprise, Routledge, and Cambridge University Press. RNC’s research is supported by the UK Medical Research Council (MC_PC_17213). T.W.R. discloses consultancy with Cambridge Cognition, Lundbeck, Mundipharma and Unilever; he receives royalties for CANTAB from Cambridge Cognition and editorial honoraria from Springer Verlag and Elsevier. T.V.L., G.S. P.S.J., A.A.M. and K.D.E. declare to have no potential conflict of interest

Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease

Parkinson’s disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID

Motor symptoms in Parkinson's disease: A unified framework

Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement

The weight of advice in older age.

Seeking advice from others may improve decision-making, particularly in older adults when cognitive decline can impair decision-making. This study measured the extent to which older adults rated the value of advice and used that advice in their decisions. Young (aged 18–37 years; n = 57) and older (aged 62–84 years; n = 56) adults completed a judge-advisor task incorporating advice from an expert and a novice. To capture interindividual differences in ratings of advice value and advice use (i.e., weight of advice), desire for autonomy, working memory, and fluid intelligence were assessed. Relative to young adults, older adults rated novice advice as being more valuable and were more likely to adjust their estimates based on expert and especially novice advice. Among older adults, poorer working memory and reduced preference for autonomous decision-making were associated with greater ratings of the value of novice advice, while better fluid intelligence was associated with increased ratings of the value of expert advice. Overall, older adults give more weight to advice and cognitive decline appears to compromise discrimination of the quality of that advice. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Reward and punishment-based compound cue learning and generalization in opiate dependency

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this recordSubstance dependence is thought to be mediated by abnormalities in cognitive abilities, but how this impacts decision-making remains unclear. This study aimed to test whether people who are opiate dependent differed from never-dependent controls in learning from reward and punishment or in the generalization of learning to novel conditions. Participants with opiate dependency consisted of 21 people who were outpatients in a methadone maintenance program; the control group consisted of 21 healthy participants with no histories of substance abuse. Subjects completed a computer-based task that involved two phases: the training phase involved participants being presented with compound stimulus (a shape and color) in each trial, with the goal of learning which compounds to 'pick' for rewards or 'skip' to avoid punishment. The test phase involved a transfer test, where stimuli from the first phase were combined together to form novel compounds without feedback. The control group demonstrated fewer errors compared to opiate-dependent individuals during the training phase. In the test phase, controls used prior knowledge of both shapes and colors in responding; however, opiate-dependent individuals used shapes but did not use their knowledge of color to modulate responding. When performance during training was equated in the groups using a learning threshold, this difference between groups on the generalization test remained. A deficit in learning generalization might be indicative of group differences in learning strategies in operation during training; however, future work is necessary to uncover the specific neural substrates in action during transfer tasks, and to determine the effects of acute methadone dosage on decision-making

A Modular Network Architecture Resolving Memory Interference through Inhibition

International audienceIn real learning paradigms like pavlovian conditioning, several modes of learning are associated, including generalization from cues and integration of specific cases in context. Associative memories have been shown to be interesting neuronal models to learn quickly specific cases but they are hardly used in realistic applications because of their limited storage capacities resulting in interferences when too many examples are considered. Inspired by biological considerations, we propose a modular model of associative memory including mechanisms to manipulate properly multimodal inputs and to detect and manage interferences. This paper reports experiments that demonstrate the good behavior of the model in a wide series of simulations and discusses its impact both in machine learning and in biological modeling

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Molecular abnormalities in autopsied brain tissue from the inferior horn of the lateral ventricles of nonagenarians and Alzheimer disease patients

Background The ventricular system plays a vital role in blood-cerebrospinal fluid (CSF) exchange and interstitial fluid-CSF drainage pathways. CSF is formed in the specialized secretory tissue called the choroid plexus, which consists of epithelial cells, fenestrated capillaries and the highly vascularized stroma. Very little is currently known about the role played by the ventricles and the choroid plexus tissue in aging and Alzheimer's disease (AD). MethodsIn this study, we used our state-of-the-art proteomic platform, a liquid chromatography/mass spectrometry (LC-MS/MS) approach coupled with Tandem Mass Tag isobaric labeling to conduct a detailed unbiased proteomic analyses of autopsied tissue isolated from the walls of the inferior horn of the lateral ventricles in AD (77.2 ± 0.6 yrs), age-matched controls (77.0 ± 0.5 yrs), and nonagenarian cases (93.2 ± 1.1 yrs). ResultsIngenuity pathway analyses identified phagosome maturation, impaired tight-junction signaling, and glucose/mannose metabolism as top significantly regulated pathways in controls vs nonagenarians. In matched-control vs AD cases we identified alterations in mitochondrial bioenergetics, oxidative stress, remodeling of epithelia adherens junction, macrophage recruitment and phagocytosis, and cytoskeletal dynamics. Nonagenarian vs AD cases demonstrated augmentation of oxidative stress, changes in gluconeogenesis-glycolysis pathways, and cellular effects of choroidal smooth muscle cell vasodilation. Amyloid plaque score uniquely correlated with remodeling of epithelial adherens junctions, Fc γ-receptor mediated phagocytosis, and alterations in RhoA signaling. Braak staging was uniquely correlated with altered iron homeostasis, superoxide radical degradation and phagosome maturation. Conclusions These changes provide novel insights to explain the compromise to the physiological properties and function of the ventricles/choroid plexus system in nonagenarian aging and AD pathogenesis. The pathways identified could provide new targets for therapeutic strategies to mitigate the divergent path towards AD