Insulin modulates emotional behavior through a serotonin-dependent mechanism.

Type-2 Diabetes (T2D) is characterized by insulin resistance and accompanied by psychiatric comorbidities including major depressive disorders (MDD). Patients with T2D are twice more likely to suffer from MDD and clinical studies have shown that insulin resistance is positively correlated with the severity of depressive symptoms. However, the potential contribution of central insulin signaling in MDD in patients with T2D remains elusive. Here we hypothesized that insulin modulates the serotonergic (5-HT) system to control emotional behavior and that insulin resistance in 5-HT neurons contributes to the development of mood disorders in T2D. Our results show that insulin directly modulates the activity of dorsal raphe (DR) 5-HT neurons to dampen 5-HT neurotransmission through a 5-HT1A receptor-mediated inhibitory feedback. In addition, insulin-induced 5-HT neuromodulation is necessary to promote anxiolytic-like effect in response to intranasal insulin delivery. Interestingly, such an anxiolytic effect of intranasal insulin as well as the response of DR 5-HT neurons to insulin are both blunted in high-fat diet-fed T2D animals. Altogether, these findings point to a novel mechanism by which insulin directly modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and control emotional behaviors, and emphasize the idea that impaired insulin-sensitivity in these neurons is critical for the development of T2D-associated mood disorders.

Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model.

Down syndrome (DS) or Trisomy 21 is the most common genetic cause of mental retardation with severe learning and memory deficits. DS is due to the complete or partial triplication of human chromosome 21 (HSA21) triggering gene overexpression and protein synthesis alterations responsible for a plethora of mental and physical phenotypes. Among the diverse brain target systems that affect hippocampal-dependent learning and memory deficit impairments in DS, the upregulation of the endocannabinoid system (ECS), and notably the overexpression of the cannabinoid type-1 receptor (CB1), seems to play a major role. Combining various protein and gene expression targeted approaches using western blot, qRT-PCR and FISH techniques, we investigated the expression pattern of ECS components in the hippocampus (HPC) of male Ts65Dn mice. Among all the molecules that constitute the ECS, we found that the expression of the CB1 is altered in the HPC of Ts65Dn mice. CB1 distribution is differentially segregated between the dorsal and ventral part of the HPC and within the different cell populations that compose the HPC. CB1 expression is upregulated in GABAergic neurons of Ts65Dn mice whereas it is downregulated in glutamatergic neurons. These results highlight a complex regulation of the CB1 encoding gene (Cnr1) in Ts65Dn mice that could open new therapeutic solutions for this syndrome.

Can Online Teaching of Radiographic Anatomy Replace Conventional On-Site Teaching? A Randomized Controlled Study.

Different modalities such as lectures, dissections, 3D models, and online learning are used for teaching anatomy. To date, online learning has been considered a useful additional didactic tool. This study aimed to compare veterinary students' performance in radiographic anatomy (radio-anatomy) after online or classroom-based teaching to assess the extent to which the two methods were interchangeable. Three strategies were compared in a cohort of 83 learners. Students were committed to online learning only, online learning with the use of specimen equine bones, or learning on conventional radiographs with specimen equine bones. At baseline (pre-test), scores from a mental rotation test and radio-anatomy knowledge test were similar between groups. After training (post-test), scores in mental rotation and radio-anatomy significantly increased by 6.7/40 units (95% CI: 5.2-8.2; p < .001) and 5.1/20 units (95% CI: 4.3-5.9; p < .001), respectively. There was no difference in scores for mental rotation and radio-anatomy knowledge between groups at post-test. Gender influenced the mental rotation, with men scoring significantly higher than women at pre-test (M = 23.0, SD = 8.8 vs. M = 16.5, SD = 6.9; p = .001) and post-test (M = 32.1, SD = 5.5 vs. M = 22.7, SD = 8.6; p < .001). However, radio-anatomy knowledge was not influenced by gender. These results suggest radio-anatomy teaching can be safely achieved with either conventional radiographs or online resources. This is of interest since, due to the COVID-19 outbreak, rapidly changing from on-site to online methods for teaching veterinary medical education proved necessary.

REM1.3's phospho-status defines its plasma membrane nanodomain organization and activity in restricting PVX cell-to-cell movement.

Plants respond to pathogens through dynamic regulation of plasma membrane-bound signaling pathways. To date, how the plant plasma membrane is involved in responses to viruses is mostly unknown. Here, we show that plant cells sense the Potato virus X (PVX) COAT PROTEIN and TRIPLE GENE BLOCK 1 proteins and subsequently trigger the activation of a membrane-bound calcium-dependent kinase. We show that the Arabidopsis thaliana CALCIUM-DEPENDENT PROTEIN KINASE 3-interacts with group 1 REMORINs in vivo, phosphorylates the intrinsically disordered N-terminal domain of the Group 1 REMORIN REM1.3, and restricts PVX cell-to-cell movement. REM1.3's phospho-status defines its plasma membrane nanodomain organization and is crucial for REM1.3-dependent restriction of PVX cell-to-cell movement by regulation of callose deposition at plasmodesmata. This study unveils plasma membrane nanodomain-associated molecular events underlying the plant immune response to viruses.

Estimating virus effective population size and selection without neutral markers.

By combining high-throughput sequencing (HTS) with experimental evolution, we can observe the within-host dynamics of pathogen variants of biomedical or ecological interest. We studied the evolutionary dynamics of five variants of Potato virus Y (PVY) in 15 doubled-haploid lines of pepper. All plants were inoculated with the same mixture of virus variants and variant frequencies were determined by HTS in eight plants of each pepper line at each of six sampling dates. We developed a method for estimating the intensities of selection and genetic drift in a multi-allelic Wright-Fisher model, applicable whether these forces are strong or weak, and in the absence of neutral markers. This method requires variant frequency determination at several time points, in independent hosts. The parameters are the selection coefficients for each PVY variant and four effective population sizes Ne at different time-points of the experiment. Numerical simulations of asexual haploid Wright-Fisher populations subjected to contrasting genetic drift (Ne ∈ [10, 2000]) and selection (|s| ∈ [0, 0.15]) regimes were used to validate the method proposed. The experiment in closely related pepper host genotypes revealed that viruses experienced a considerable diversity of selection and genetic drift regimes. The resulting variant dynamics were accurately described by Wright-Fisher models. The fitness ranks of the variants were almost identical between host genotypes. By contrast, the dynamics of Ne were highly variable, although a bottleneck was often identified during the systemic movement of the virus. We demonstrated that, for a fixed initial PVY population, virus effective population size is a heritable trait in plants. These findings pave the way for the breeding of plant varieties exposing viruses to stronger genetic drift, thereby slowing virus adaptation.

Apprendre l'anatomie radiographique en présentiel ou en ligne ? Une étude randomisée contrôlée.

Résumé L'enseignement de l'anatomie repose sur diverses techniques: les cours, les dissections, les modèles 3D ou encore les supports en ligne. Ces derniers sont généralement considérés comme des moyens d'apprentissage complémentaires. Cette étude vise à comparer les performances des étudiants vétérinaires (N=83) en anatomie radiographique (radioanatomie) après un apprentissage en ligne ou conventionnel, et de voir dans quelle mesure ces méthodes sont interchangeables. Trois stratégies sont comparées : apprentissage en ligne exclusif, apprentissage en ligne avec des os de chevaux, apprentissage sur radiographies conventionnelles avec des os de chevaux. Les performances au test de rotation mentale et au test de connaissance en radioanatomie sont similaires entre les 3 groupes à la base, lors du test préliminaire. Après l'apprentissage (test final), les scores de rotation mentale et de radioanatomie augment significativement de 6.7/40 points (CI : 5.2­8.2; p < .001) et de 5.1/20 points (CI: 4.3­5.9; p< .001). Il n'y a pas de différence entre les groupes pour les scores de rotation mentale et de radioanatomie après l'apprentissage. Le score de rotation mentale est influencé par le genre, et significativement plus élevé chez les hommes que chez les femmes au test préliminaire (M= 23.0, SD = 8.8 vs. M= 16.5, SD= 6.9; p= .001) et au test final (M= 32.1, SD= 5.5 vs. M= 22.7, SD= 8.6; p< .001). Les performances en radioanatomie ne sont pas influencées par le genre. Ces résultats suggèrent que l'enseignement de la radioanatomie peut être réalisé en présentiel avec des radiographies conventionnelles ou en ligne. Cette interchangeabilité entre apprentissage en présentiel et en distanciel est intéressante au regard des impératifs liés aux crises sanitaires, et des besoins d'adaptation rapide en distanciel. This translation was provided by the authors. To view the original article visit: https://doi.org/10.3138/jvme-2021-0153.

Genetic Determinism and Evolutionary Reconstruction of a Host Jump in a Plant Virus.

In spite of their widespread occurrence, only few host jumps by plant viruses have been evidenced and the molecular bases of even fewer have been determined. A combination of three independent approaches, 1) experimental evolution followed by reverse genetics analysis, 2) positive selection analysis, and 3) locus-by-locus analysis of molecular variance (AMOVA) allowed reconstructing the Potato virus Y (PVY; genus Potyvirus, family Potyviridae) jump to pepper (Capsicum annuum), probably from other solanaceous plants. Synthetic chimeras between infectious cDNA clones of two PVY isolates with contrasted levels of adaptation to C. annuum showed that the P3 and, to a lower extent, the CI cistron played important roles in infectivity toward C. annuum. The three analytical approaches pinpointed a single nonsynonymous substitution in the P3 and P3N-PIPO cistrons that evolved several times independently and conferred adaptation to C. annuum. In addition to increasing our knowledge of host jumps in plant viruses, this study illustrates also the efficiency of locus-by-locus AMOVA and combined approaches to identify adaptive mutations in the genome of RNA viruses.

Accuracy of computed tomographic arthrography for assessment of articular cartilage defects in the ovine stifle.

Articular cartilage defects are one of the features of osteoarthritis in animals and humans. Early detection of cartilage defects is a challenge in clinical veterinary practice and also in translational research studies. An accurate, diagnostic imaging method would be desirable for detecting and following up lesions in specific anatomical regions of the articular surface. The current prospective experimental study aimed to describe the accuracy of computed tomographic arthrography (CTA) for detecting cartilage defects in a common animal model used for osteoarthritis research, the ovine stifle (knee, femoropatellar/femorotibial) joint. Joints in cadaver limbs (n = 42) and in living animals under anesthesia (n = 13) were injected with a contrast medium and imaged using a standardized CT protocol. Gross anatomy and histological assessment of specific anatomic regions were used as a gold standard for the evaluation of sensitivity, specificity, negative predictive value, and positive predictive value for CTA identification of articular cartilage defects in those regions. Pooled estimated sensitivity and specificity were 90.32% and 97.30%, respectively, in cadaver limbs, and 81.82% and 95.24%, respectively, in living animals. Pooled estimated positive predictive value and negative predictive values were 98.25% and 85.71%, respectively, in cadaver limbs, and 81.82% and 95.24%, respectively, in living animals. The delineation of cartilage surface was good for anatomical regions most frequently affected by cartilage defects in the ovine stifle: medial femoral condyle, medial tibial condyle, and patella. This study supported the use of CTA as an imaging technique for detecting and monitoring articular cartilage defects in the ovine stifle joint.

Narrow bottlenecks affect Pea seedborne mosaic virus populations during vertical seed transmission but not during leaf colonization.

The effective size of populations (Ne) determines whether selection or genetic drift is the predominant force shaping their genetic structure and evolution. Populations having high Ne adapt faster, as selection acts more intensely, than populations having low Ne, where random effects of genetic drift dominate. Estimating Ne for various steps of plant virus life cycle has been the focus of several studies in the last decade, but no estimates are available for the vertical transmission of plant viruses, although virus seed transmission is economically significant in at least 18% of plant viruses in at least one plant species. Here we study the co-dynamics of two variants of Pea seedborne mosaic virus (PSbMV) colonizing leaves of pea plants (Pisum sativum L.) during the whole flowering period, and their subsequent transmission to plant progeny through seeds. Whereas classical estimators of Ne could be used for leaf infection at the systemic level, as virus variants were equally competitive, dedicated stochastic models were needed to estimate Ne during vertical transmission. Very little genetic drift was observed during the infection of apical leaves, with Ne values ranging from 59 to 216. In contrast, a very drastic genetic drift was observed during vertical transmission, with an average number of infectious virus particles contributing to the infection of a seedling from an infected mother plant close to one. A simple model of vertical transmission, assuming a cumulative action of virus infectious particles and a virus density threshold required for vertical transmission to occur fitted the experimental data very satisfactorily. This study reveals that vertically-transmitted viruses endure bottlenecks as narrow as those imposed by horizontal transmission. These bottlenecks are likely to slow down virus adaptation and could decrease virus fitness and virulence.

Interaction patterns between potato virus Y and eIF4E-mediated recessive resistance in the Solanaceae.

UNLABELLED: The structural pattern of infectivity matrices, which contains infection data resulting from inoculations of a set of hosts by a set of parasites, is a key parameter for our understanding of biological interactions and their evolution. This pattern determines the evolution of parasite pathogenicity and host resistance, the spatiotemporal distribution of host and parasite genotypes, and the efficiency of disease control strategies. Two major patterns have been proposed for plant-virus genotype infectivity matrices. In the gene-for-gene model, infectivity matrices show a nested pattern, where the host ranges of specialist virus genotypes are subsets of the host ranges of less specialized viruses. In contrast, in the matching-allele (MA) model, each virus genotype is specialized to infect one (or a small set of) host genotype(s). The corresponding infectivity matrix shows a modular pattern where infection is frequent for plants and viruses belonging to the same module but rare for those belonging to different modules. We analyzed the structure of infectivity matrices between Potato virus Y (PVY) and plant genotypes in the family Solanaceae carrying different eukaryotic initiation factor 4E (eIF4E)-coding alleles conferring recessive resistance. Whereas this system corresponds mechanistically to an MA model, the expected modular pattern was rejected based on our experimental data. This was mostly because PVY mutations involved in adaptation to a particular plant genotype displayed frequent pleiotropic effects, conferring simultaneously an adaptation to additional plant genotypes with different eIF4E alleles. Such effects should be taken into account for the design of strategies of sustainable control of PVY through plant varietal mixtures or rotations. IMPORTANCE: The interaction pattern between host and virus genotypes has important consequences on their respective evolution and on issues regarding the application of disease control strategies. We found that the structure of the interaction between Potato virus Y (PVY) variants and host plants in the family Solanaceae departs significantly from the current model of interaction considered for these organisms because of frequent pleiotropic effects of virus mutations. These mutational effects allow the virus to expand rapidly its range of host plant genotypes, make it very difficult to predict the effects of mutations in PVY infectivity factors, and raise concerns about strategies of sustainable management of plant genetic resistance to viruses.

Modelling the evolutionary dynamics of viruses within their hosts: a case study using high-throughput sequencing.

Uncovering how natural selection and genetic drift shape the evolutionary dynamics of virus populations within their hosts can pave the way to a better understanding of virus emergence. Mathematical models already play a leading role in these studies and are intended to predict future emergences. Here, using high-throughput sequencing, we analyzed the within-host population dynamics of four Potato virus Y (PVY) variants differing at most by two substitutions involved in pathogenicity properties. Model selection procedures were used to compare experimental results to six hypotheses regarding competitiveness and intensity of genetic drift experienced by viruses during host plant colonization. Results indicated that the frequencies of variants were well described using Lotka-Volterra models where the competition coefficients ß(ij) exerted by variant j on variant i are equal to their fitness ratio, r(j)/r(i). Statistical inference allowed the estimation of the effect of each mutation on fitness, revealing slight (s = -0.45%) and high (s = -13.2%) fitness costs and a negative epistasis between them. Results also indicated that only 1 to 4 infectious units initiated the population of one apical leaf. The between-host variances of the variant frequencies were described using Dirichlet-multinomial distributions whose scale parameters, closely related to the fixation index F(ST), were shown to vary with time. The genetic differentiation of virus populations among plants increased from 0 to 10 days post-inoculation and then decreased until 35 days. Overall, this study showed that mathematical models can accurately describe both selection and genetic drift processes shaping the evolutionary dynamics of viruses within their hosts.

AtHVA22a, a plant-specific homologue of Reep/DP1/Yop1 family proteins is involved in turnip mosaic virus propagation.

The movement of potyviruses, the largest genus of single-stranded, positive-sense RNA viruses responsible for serious diseases in crops, is very complex. As potyviruses developed strategies to hijack the host secretory pathway and plasmodesmata (PD) for their transport, the goal of this study was to identify membrane and/or PD-proteins that interact with the 6K2 protein, a potyviral protein involved in replication and cell-to-cell movement of turnip mosaic virus (TuMV). Using split-ubiquitin membrane yeast two-hybrid assays, we screened an Arabidopsis cDNA library for interactors of TuMV6K2. We isolated AtHVA22a (Hordeum vulgare abscisic acid responsive gene 22), which belongs to a multigenic family of transmembrane proteins, homologous to Receptor expression-enhancing protein (Reep)/Deleted in polyposis (DP1)/Yop1 family proteins in animal and yeast. HVA22/DP1/Yop1 family genes are widely distributed in eukaryotes, but the role of HVA22 proteins in plants is still not well known, although proteomics analysis of PD fractions purified from Arabidopsis suspension cells showed that AtHVA22a is highly enriched in a PD proteome. We confirmed the interaction between TuMV6K2 and AtHVA22a in yeast, as well as in planta by using bimolecular fluorescence complementation and showed that TuMV6K2/AtHVA22a interaction occurs at the level of the viral replication compartment during TuMV infection. Finally, we showed that the propagation of TuMV is increased when AtHVA22a is overexpressed in planta but slowed down upon mutagenesis of AtHVA22a by CRISPR-Cas9. Altogether, our results indicate that AtHVA22a plays an agonistic effect on TuMV propagation and that the C-terminal tail of the protein is important in this process.

Single cell tracing of Pomc neurons reveals recruitment of 'Ghost' subtypes with atypical identity in a mouse model of obesity.

The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of 'Ghost' neurons endowed with atypical molecular and functional identity. Compared to 'classical' Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are 'invisible' to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.

High prevalence of poleroviruses in field-grown pepper in Turkey and Tunisia.

Open-field pepper crops were sampled in 2011 in Turkey and Tunisia and surveyed for the major pepper-infecting viruses. As expected, potato virus Y and cucumber mosaic virus (in both countries), and tobacco etch virus (in Turkey only) were quite frequent. However, poleroviruses were the most common viruses, with prevalences above 70 %. Partial sequence analyses revealed the occurrence of poleroviruses resembling either beet western yellows virus (BWYV) or pepper vein yellows virus in the sampled areas, with BWYV being predominant in Turkey but in the minority in Tunisia. Poleroviruses should therefore be taken into account in disease control of pepper crops in the Mediterranean area.

A Single Nonsynonymous Substitution in the RNA-Dependent RNA Polymerase of Potato virus Y Allows the Simultaneous Breakdown of Two Different Forms of Antiviral Resistance in Capsicum annuum.

The dominant Pvr4 gene in pepper (Capsicum annuum) confers resistance to members of six potyvirus species, all of which belong to the Potato virus Y (PVY) phylogenetic group. The corresponding avirulence factor in the PVY genome is the NIb cistron (i.e., RNA-dependent RNA polymerase). Here, we describe a new source of potyvirus resistance in the Guatemalan accession C. annuum cv. PM949. PM949 is resistant to members of at least three potyvirus species, a subset of those controlled by Pvr4. The F1 progeny between PM949 and the susceptible cultivar Yolo Wonder was susceptible to PVY, indicating that the resistance is recessive. The segregation ratio between resistant and susceptible plants observed in the F2 progeny matched preferably with resistance being determined by two unlinked recessive genes independently conferring resistance to PVY. Inoculations by grafting resulted in the selection of PVY mutants breaking PM949 resistance and, less efficiently, Pvr4-mediated resistance. The codon substitution E472K in the NIb cistron of PVY, which was shown previously to be sufficient to break Pvr4 resistance, was also sufficient to break PM949 resistance, a rare example of cross-pathogenicity effect. In contrast, the other selected NIb mutants showed specific infectivity in PM949 or Pvr4 plants. Comparison of Pvr4 and PM949 resistance, which share the same target in PVY, provides interesting insights into the determinants of resistance durability.

An Ex Vivo Pilot Study to Assess the Feasibility of 3D Printing of Orbital Implants in Horses.

Severe ophthalmic conditions such as trauma, uveitis, corneal damage, or neoplasia can lead to eye removal surgery. Poor cosmetic appearance resulting from the sunken orbit ensues. The aim of this study was to demonstrate the feasibility of manufacturing a custom-made 3D-printed orbital implant made of biocompatible material for the enucleated horse and usable in conjunction to a corneoscleral shell. Blender, a 3D-image software, was used for prototype design. Twelve cadaver heads of adult Warmbloods were collected from the slaughterhouse. On each head, one eye was removed via a modified transconjunctival enucleation while the contralateral eye was kept intact as control. Ocular measurements were collected on each enucleated eye with the help of a caliper and used for prototype sizing. Twelve custom-made biocompatible porous prototypes were 3D-printed in BioMed Clear resin using the stereolithography technique. Each implant was fixated into the corresponding orbit, within the Tenon capsule and conjunctiva. Heads were frozen and thin slices were then cut in the transverse plane. A scoring system based on four criteria (space for ocular prosthesis, soft-tissue-coverage, symmetry to the septum, and horizontal symmetry), ranging from A (proper fixation) to C (poor fixation), was developed to evaluate implantation. The prototypes reached our expectations: 75% of the heads received an A score, and 25% a B score. Each implant cost approximately 7.30€ and took 5 hours for 3D-printing. The production of an economically accessible orbital implant made of biocompatible porous material was successful. Further studies will help determine if the present prototype is usable in vivo.

dN/dS-based methods detect positive selection linked to trade-offs between different fitness traits in the coat protein of potato virus Y.

The dN/dS ratio between nonsynonymous and synonymous substitution rates has been used extensively to identify codon positions involved in adaptive processes. However, the accuracy of this approach has been questioned, and very few studies have attempted to validate experimentally its predictions. Using the coat protein (CP) of Potato virus Y (PVY; genus Potyvirus, family Potyviridae) as a case study, we identified several candidate positively selected codon positions that differed between clades. In the CP of the N clade of PVY, positive selection was detected at codon positions 25 and 68 by both the softwares PAML and HyPhy. We introduced nonsynonymous substitutions at these positions in an infectious cDNA clone of PVY and measured the effect of these mutations on virus accumulation in its two major cultivated hosts, tobacco and potato, and on its efficiency of transmission from plant to plant by aphid vectors. The mutation at codon position 25 significantly modified the virus accumulation in the two hosts, whereas the mutation at codon position 68 significantly modified the virus accumulation in one of its hosts and its transmissibility by aphids. Both mutations were involved in adaptive trade-offs. We suggest that our study was particularly favorable to the detection of adaptive mutations using dN/dS estimates because, as obligate parasites, viruses undergo a continuous and dynamic interaction with their hosts that favors the recurrent selection of adaptive mutations and because trade-offs between different fitness traits impede (or at least slow down) the fixation of these mutations and maintain polymorphism within populations.

StREM1.3 REMORIN Protein Plays an Agonistic Role in Potyvirus Cell-to-Cell Movement in N. benthamiana.

REMORIN proteins belong to a plant-specific multigene family that localise in plasma membrane nanodomains and in plasmodesmata. We previously showed that in Nicotiana benthamiana, group 1 StREM1.3 limits the cell-to-cell spread of a potexvirus without affecting viral replication. This prompted us to check whether an effect on viral propagation could apply to potyvirus species Turnip mosaic virus (TuMV) and Potato virus A (PVA). Our results show that StREM1.3 transient or stable overexpression in transgenic lines increases potyvirus propagation, while it is slowed down in transgenic lines underexpressing endogenous NbREMs, without affecting viral replication. TuMV and PVA infection do not alter the membranous localisation of StREM1.3. Furthermore, StREM1.3-membrane anchoring is necessary for its agonist effect on potyvirus propagation. StREM1.3 phosphocode seems to lead to distinct plant responses against potexvirus and potyvirus. We also showed that StREM1.3 interacts in yeast and in planta with the key potyviral movement protein CI (cylindrical inclusion) at the level of the plasma membrane but only partially at plasmodesmata pit fields. TuMV infection also counteracts StREM1.3-induced plasmodesmata callose accumulation at plasmodesmata. Altogether, these results showed that StREM1.3 plays an agonistic role in potyvirus cell-to-cell movement in N. benthamiana.

Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer's disease.

Increasing evidence shows that hypothalamic dysfunction, insulin resistance, and weight loss precede and progress along with the cognitive decline in sporadic Alzheimer's Disease (AD) with sex differences. This study aimed to determine the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance associated with polycystic ovary, on the occurrence of metabolic disorders in the transgenic 5xFAD mouse model of AD (FAD: Family Alzheimer's Disease). DCI was administered from 6 to 10 months of age to male and female 5xFAD mice and control (non-Tg) littermates. Energy balance and multiple metabolic and inflammatory parameters in the hypothalamus, liver and plasma were evaluated to assess the central and peripheral effects of DCI. Results indicated that weight loss and reduced food intake in 5xFAD mice were associated with decreased neuropeptides controlling food intake and the appearance of a pro-inflammatory state in the hypothalamus. Oral administration of DCI partially restored energy balance and hypothalamic parameters, highlighting an increased expression of Npy and Agrp and female-specific downregulation of Gfap and Igf1. DCI also partially normalized impaired insulin signaling and circulating insulin, GLP-1, and GIP deficiencies in 5xFAD mice. Principal component analysis of metabolic parameters indicated the presence of a female-specific fatty liver in 5xFAD mice: DCI administration reversed hepatic fat accumulation, ß-oxidation, inflammation and increased GOT and GPT levels. Our study depicts that metabolic impairment along with the cognitive decline in a mouse model of AD, which is exacerbated in females, can be ameliorated by oral supplementation with insulin-sensitizing DCI.

The helper component proteinase cistron of Potato virus Y induces hypersensitivity and resistance in Potato genotypes carrying dominant resistance genes on chromosome IV.

The Nc(tbr) and Ny(tbr) genes in Solanum tuberosum determine hypersensitive reactions, characterized by necrotic reactions and restriction of the virus systemic movement, toward isolates belonging to clade C and clade O of Potato virus Y (PVY), respectively. We describe a new resistance from S. sparsipilum which possesses the same phenotype and specificity as Nc(tbr) and is controlled by a dominant gene designated Nc(spl). Nc(spl) maps on potato chromosome IV close or allelic to Ny(tbr). The helper component proteinase (HC-Pro) cistron of PVY was shown to control necrotic reactions and resistance elicitation in plants carrying Nc(spl), Nc(tbr), and Ny(tbr). However, inductions of necrosis and of resistance to the systemic virus movement in plants carrying Nc(spl) reside in different regions of the HC-Pro cistron. Also, genomic determinants outside the HC-Pro cistron are involved in the systemic movement of PVY after induction of necroses on inoculated leaves of plants carrying Ny(tbr). These results suggest that the Ny(tbr) resistance may have been involved in the recent emergence of PVY isolates with a recombination breakpoint near the junction of HC-Pro and P3 cistrons in potato crops. Therefore, this emergence could constitute one of the rare examples of resistance breakdown by a virus which was caused by recombination instead of by successive accumulation of nucleotide substitutions.