Subcolumnar Dendritic and Axonal Organization of Spiny Stellate and Star Pyramid Neurons within a Barrel in Rat Somatosensory Cortex

Excitatory neurons at the level of cortical layer 4 in the rodent somatosensory barrel field often display a strong eccentricity in comparison with layer 4 neurons in other cortical regions. In rat, dendritic symmetry of the 2 main excitatory neuronal classes, spiny stellate and star pyramid neurons (SSNs and SPNs), was quantified by an asymmetry index, the dendrite-free angle. We carefully measured shrinkage and analyzed its influence on morphological parameters. SSNs had mostly eccentric morphology, whereas SPNs were nearly radially symmetric. Most asymmetric neurons were located near the barrel border. The axonal projections, analyzed at the level of layer 4, were mostly restricted to a single barrel except for those of 3 interbarrel projection neurons. Comparing voxel representations of dendrites and axon collaterals of the same neuron revealed a close overlap of dendritic and axonal fields, more pronounced in SSNs versus SPNs and considerably stronger in spiny L4 neurons versus extragranular pyramidal cells. These observations suggest that within a barrel dendrites and axons of individual excitatory cells are organized in subcolumns that may confer receptive field properties such as directional selectivity to higher layers, whereas the interbarrel projections challenge our view of barrels as completely independent processors of thalamic inpu

A Herschel view of IC 1396 A: Unveiling the different sequences of star formation

The IC1396A globule in the young cluster Tr37, hosting many young stars and protostars, is assumed to be a site of triggered star formation. We mapped IC1396A with Herschel/PACS at 70 and 160 micron. The Herschel maps trace in great detail the very embedded protostellar objects and the structure of the cloud. PACS data reveal a previously unknown Class 0 object (IC1396A-PACS-1) located behind the ionization front. IC1396A-PACS-1 is not detectable with Spitzer, but shows marginal X-ray emission. The data also allowed to study three of the Class I intermediate-mass objects within the cloud. We derived approximate cloud temperatures to study the effect and potential interactions between the protostars and the cloud. The Class 0 object is associated with the densest and colder part of IC1396A. Heating in the cloud is dominated by the winds and radiation of the O6.5 star HD 206267 and, to a lesser extent, by the effects of the Herbig Ae star V 390 Cep. The surroundings of the Class I and Class II objects embedded in the cloud also appear warmer than the sourceless areas, although most of the low-mass objects cannot be individually extracted due to distance and beam dilution. The observations suggest that at least two episodes of star formation have occurred in IC1396A. One would have originated the known, ~1 Myr-old Class I and II objects in the cloud, and a new wave of star formation would have produced the Class 0 source at the tip of the brigth-rimmed cloud. From its location and properties, IC1396A-PACS-1 is consistent with triggering via radiative driven implosion (RDI) induced by HD 206267. The mechanisms behind the formation of the more evolved population of Class I/II/III objects in the cloud are uncertain. Heating of most of the remaining cloud by Class I/Class II objects and by HD 206267 itself may preclude further star formation in the region.Comment: Accepted by A&A, 9 pages, 5 figure

Palynological characterization of the Po delta succession (northern Italy): Holocene vegetation dynamics, stratigraphic patterns and palaeoclimate variability

The 40 m-long core EM2, recovered in the innermost portion of Po delta plain, was sampled for palynological analysis, in order to link coastal-deltaic facies architecture to vegetation dynamics and Holocene climate variability. Pollen data refine facies characterization of the 25 m-thick Holocene succession: freshwater swamp clays alternating with overbank/channel sands document millennial to centennial-scale water table oscillations that invariably peak in correspondence of peaty layers. Pollen signature allows identification of the landward equivalent of the Maximum Flooding Surface atop the 7.6 ka-dated peaty interval and furnishes new insights on the relationship between coastal facies patterns and climate events

Dynamics of a polymerization model on a graph

This work is concerned with the dynamics of a polymerization process coupled with mass transfer and monomers injection, modeled by means of an infinite-dimensional system of Smoluchowski's equations in a finite graph. Under suitable assumptions on the system's aggregation coefficients, we show that, as a consequence of the injection mechanism, a sizable depletion of the pool of available reacting substances  occurs at some finite time, that can be estimated in terms of the parameters of the problem. By analogy with well-known results in chemical engineering, we interpret that result as the onset of a sol-gel phase transition. We suggest that this property might have some interest in the mathematical modeling of neurodegenerative processes, where the polymerization of some soluble proteins and their eventual aggregation into insoluble plaques play a remarkable role, which is not well understood as yet

The role of beta-amyloid and tau proteins in Alzheimer's disease: a mathematical model on graph

In this Note we study a mathematical model for the progression of Alzheimer's Disease in the human brain. The novelty of our approach consists in the representation of the brain as two superposed graphs where toxic proteins diffuse, the connectivity graph which represents the neural network, and the proximity graph which takes into account the extracellular space. Toxic proteins such as beta-amyloid and tau play in fact a crucial role in the development of Alzheimer's disease and, separately, have been targets of medical treatments. Recent biomedical literature stresses the potential impact of the synergetic action of these proteins. We numerically test various modelling hypotheses which confirm the relevance of this synergy

One Protein to Rule them All: Modulation of Cell Surface Receptors and Molecules by HIV Nef

The HIV-1, HIV-2 and SIV Nef protein are known to modulate the expression of several cell surface receptors and molecules to escape the immune system, to alter T cell activation, to enhance viral replication, infectivity and transmission and overall to ensure the optimal environment for infection outcome. Consistent and continuous efforts have been made over the years to characterize the modulation of expression of each of these molecules, in the hope that a better understanding of these processes essential for HIV infection and/or pathogenesis will eventually highlight new therapeutic targets. In this article we provide an extensive review of the knowledge gained so far on this important and evolving topic

Pain in monogenic Parkinson’s disease: a comprehensive review

Pain, a challenging symptom experienced by individuals diagnosed with Parkinson’s disease (PD), still lacks a comprehensive understanding of its underlying pathophysiological mechanisms. A systematic investigation of its prevalence and impact on the quality of life in patients affected by monogenic forms of PD has yet to be undertaken. This comprehensive review aims to provide an overview of the association between pain and monogenic forms of PD, specifically focusing on pathogenic variants in SNCA, PRKN, PINK1, PARK7, LRRK2, GBA1, VPS35, ATP13A2, DNAJC6, FBXO7, and SYNJ1. Sixty-three articles discussing pain associated with monogenic PD were identified and analyzed. The included studies exhibited significant heterogeneity in design, sample size, and pain outcome measures. Nonetheless, the findings of this review suggest that patients with monogenic PD may experience specific types of pain depending on the pathogenic variant present, distinguishing them from non-carriers. For instance, individuals with SNCA pathogenic variants have reported painful dystonia, lower extremity pain, dorsal pain, and upper back pain. However, these observations are primarily based on case reports with unclear prevalence. Painful lower limb dystonia and lower back pain are prominent symptoms in PRKN carriers. A continual correlation has been noted between LRRK2 mutations and the emergence of pain, though the conflicting research outcomes pose challenges in reaching definitive conclusions. Individuals with PINK1 mutation carriers also frequently report experiencing pain. Pain has been frequently reported as an initial symptom and the most troublesome one in GBA1-PD patients compared to those with idiopathic PD. The evidence regarding pain in ATP13A2, PARK7, VPS35, DNAJC6, FBXO7, and SYNJ1pathogenic variants is limited and insufficient. The potential linkage between genetic profiles and pain outcomes holds promising clinical implications, allowing for the potential stratification of patients in clinical trials and the development of personalized treatments for pain in monogenic PD. In conclusion, this review underscores the need for further research to unravel the intricate relationship between pain and monogenic forms of PD. Standardized methodologies, larger sample sizes, and longitudinal studies are essential to elucidate the underlying mechanisms and develop targeted therapeutic interventions for pain management in individuals with monogenic PD

Utilisation des toxines botuliniques pour soulager la douleur réfractaire et d’autres symptômes du parkinsonisme

Background: Parkinson's disease (PD) and other parkinsonian syndromes are chronic, progressive neurodegenerative diseases. With advancing disease, both motor and non-motor symptoms represent a considerable burden and symptom relief and quality of life improvement become the main goal of treatment. Botulinum toxins (BTX) are an effective treatment modality for many neurological conditions. Methods: To understand the potential usefulness of BTX in this population, we performed a retrospective chart review of all patients with a clinical diagnosis of idiopathic PD and atypical parkinsonism who received treatment with BTX injections in our center from 1995 to 2014 for a variety of symptoms. Response to BTX was assessed using a subjective Clinical Global Impression. Results: Records of 160 patients were reviewed. Probable idiopathic PD was the diagnosis in 117 patients (73.1%). The main indication for BTX treatment was pain (50.6% of cases). Other indications were the treatment of functional impairment resulting from dystonia (26.25%), sialorrhea (18.75%), freezing of gait, and camptocormia. Considering pain as indication, 81% of all patients with PD reported benefits after the first BTX injections. This benefit was maintained after the last recorded visit without significant difference in outcome compared with the first injection (p=0.067). Similar results were observed in patients with atypical parkinsonism. Conclusions: Our results confirm the safety and efficacy of different uses of BTX in the symptomatic treatment of patients with parkinsonism even in advanced stages of the disease, and suggest BTX treatment could have a safe and useful role in the treatment of pain in this population.Contexte: La maladie de Parkinson (MP) et les divers syndromes parkinsoniens sont des affections neuro-dégénératives chroniques et évolutives. Avec la progression de la maladie, tant ses symptômes moteurs que ses symptômes non-moteurs finissent par représenter un fardeau considérable. Le soulagement de ces symptômes et l’amélioration de la qualité de vie des patients deviennent alors le principal objectif d’un traitement. À cet égard, les toxines botuliniques (« BTX ») demeurent une modalité de traitement efficace dans le cas de nombreux troubles neurologiques. Méthodes: Afin de comprendre l’utilité potentielle des toxines botuliniques, nous avons procédé à un examen rétrospectif des dossiers de tous les patients qui, après avoir reçu un diagnostic de MP idiopathique et de syndrome parkinsonien atypique, ont bénéficié dans notre centre, de 1995 à 2014, d’un traitement par injection de toxines botuliniques pour toute une gamme de symptômes. La réponse à ces toxines a ensuite été évaluée au moyen de l’échelle Clinical Global Impression. Résultats: Nous avons passé en revue les dossiers de 160 patients. Des cas probables de MP idiopathiques ont été diagnostiqués chez 117 patients (73,1 %). Fait à noter, le soulagement de la douleur était le principal motif justifiant un traitement par injection de toxines botuliniques (50,6 % des cas). D’autres motifs étaient avancés : traiter un handicap fonctionnel résultant de la dystonie (26,25 %), la sialorrhée (18,75 %), des blocages (freezing of gait) et la camptocormie. Si l’on s’en tient à la douleur, 81 % des patients atteints de la MP ont signalé des bienfaits à la suite des premières injections de toxines botuliniques. Ces bienfaits ont perduré après leur dernière visite attestée, et ce, sans qu’on ait observé de différences significatives dans les résultats par rapport à la première injection (p = 0,067). Des résultats identiques ont été constatés chez des patients atteints d’un syndrome parkinsonien atypique. Conclusions: Nos résultats confirment à la fois la sécurité et l’efficacité des différents usages des toxines botuliniques dans le soulagement, même à un stade avancé, des symptômes de patients atteints de parkinsonisme. Ils suggèrent aussi qu’un traitement par injection de toxines botuliniques pourrait, sans danger, jouer un rôle utile dans le traitement de la douleur éprouvée par cette catégorie de patients.Fil: Bruno, Veronica Andrea. University Health Network. Toronto Western Hospital; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fox, Susan H.. University Health Network. Toronto Western Hospital; CanadáFil: Mancini, Deborah. University Health Network. Toronto Western Hospital; CanadáFil: Miyasaki, Janis M.. University of Alberta; Canad

Kinematics Adaptation and Inter-Limb Symmetry during Gait in Obese Adults

The main purpose of this study is to characterize lower limb joint kinematics during gait in obese individuals by analyzing inter-limb symmetry and angular trends of lower limb joints during walking. To this purpose, 26 obese individuals (mean age 28.5 years) and 26 normal-weight age- and sex-matched were tested using 3D gait analysis. Raw kinematic data were processed to derive joint-specific angle trends and angle-angle diagrams (synchronized cyclograms) which were characterized in terms of area, orientation and trend symmetry parameters. The results show that obese individuals exhibit a kinematic pattern which significantly differs from those of normal weight especially in the stance phase. In terms of inter-limb symmetry, higher values were found in obese individuals for all the considered parameters, even though the statistical significance was detected only in the case of trend symmetry index at ankle joint. The described alterations of gait kinematics in the obese individuals and especially the results on gait asymmetry are important, because the cyclic uneven movement repeated for hours daily can involve asymmetrical spine loading and cause lumbar pain and could be dangerous for overweight individuals