Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease.

Parkinson's disease (PD) evolves over an extended and variable period in humans; years prior to the onset of classical motor symptoms, sleep and biological rhythm disorders develop, significantly impacting the quality-of-life of patients. Circadian-rhythm disorders are accompanied by mild cognitive deficits that progressively worsen with disease progression and can constitute a severe burden for patients at later stages. The gold-standard 6-methyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) macaque model of PD recapitulates the progression of motor and nonmotor symptoms over contracted periods of time.

Nationwide implementation of the self-management program "Living well with COPD": Process and effectiveness evaluation using a mixed-methods approach.

Objective: To evaluate the nationwide implementation of the "Living well with COPD" program by the Swiss Lung Association in various cantons in Switzerland.

Methods: For the process evaluation, we used qualitative (interview, focus group) and quantitative (questionnaires, documentation analysis) methods to assess the implementation outcomes reach, dose, fidelity and acceptability. For the effectiveness, we performed a pre-post analysis of patient data collected at baseline and program end (after 14 months).

Radial Migration Dynamics Is Modulated in a Laminar and Area-Specific Manner During Primate Corticogenesis.

The orderly radial migration of cortical neurons from their birthplace in the germinal zones to their final destination in the cortical plate is a prerequisite for the functional assembly of microcircuits in the neocortex. Rodent and primate corticogenesis differ both quantitatively and qualitatively, particularly with respect to the generation of neurons of the supragranular layers. Marked area differences in the outer subventricular zone progenitor cell density impact the radial glia scaffold compactness which is likely to induce area differences in radial migration strategy.

Expression of TAM-R in Human Immune Cells and Unique Regulatory Function of MerTK in IL-10 Production by Tolerogenic DC.

Tumor-infiltrating myeloid cells are a key component of the immune infiltrate often correlated with a poor prognosis due to their capacities to sustain an immunosuppressive environment. Among membrane receptors implicated in myeloid cell functions, Tyro3, Axl, and MerTK, which are a family of tyrosine kinase receptors (TAM-R), have been described in the regulation of innate cell functions. Here, we have identified MerTK among TAM-R as the major marker of both human M2 macrophages and tolerogenic dendritic cells (DC).

Unique Features of Subcortical Circuits in a Macaque Model of Congenital Blindness.

There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia.

Refinement of the Primate Corticospinal Pathway During Prenatal Development.

Perturbation of the developmental refinement of the corticospinal (CS) pathway leads to motor disorders. While non-primate developmental refinement is well documented, in primates invasive investigations of the developing CS pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. Here, we investigated the developmental changes in the distribution of CS projection neurons in cynomolgus monkey (Macaca fascicularis).

How Areal Specification Shapes the Local and Interareal Circuits in a Macaque Model of Congenital Blindness.

There is little understanding of the structural underpinnings of the functional reorganization of the cortex in the congenitally blind human. Taking advantage of the extensive characterization of the macaque visual system, we examine in macaque the influence of congenital blindness resulting from the removal of the retina during in utero development. This effectively removes the normal influence of the thalamus on cortical development leading to an induced hybrid cortex (HC) combining features of primary visual and extrastriate cortex.

Risk of Sleepiness-Related Accidents in Switzerland: Results of an Online Sleep Apnea Risk Questionnaire and Awareness Campaigns.

Objectives: Obstructive sleep apnea syndrome (OSAS) is associated with major morbidity and mortality but OSAS is frequently under recognized. To promote awareness of OSAS, the Swiss Lung League launched an online questionnaire combined with annual advertisements in mass media. Characteristics of participants, prevalence of sleep apnea, OSAS-related symptoms, and their association with accidents were investigated.

Non-invasive high-intensity focused ultrasound treatment of the placenta: a preliminary in-vivo study using a simian model.

Objective: To demonstrate the feasibility and efficacy of high-intensity focused ultrasound (HIFU) for the non-invasive creation of placental lesions in a simian model.

Methods: Eight pregnant monkeys were exposed to HIFU treatment after anesthesia, using a toroidal HIFU 2.5-MHz transducer with an integrated ultrasound imaging probe.

Anatomy of hierarchy: feedforward and feedback pathways in macaque visual cortex.

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]).

The role of long-range connections on the specificity of the macaque interareal cortical network.

We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections.

A weighted and directed interareal connectivity matrix for macaque cerebral cortex.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions.

Weight consistency specifies regularities of macaque cortical networks.

To what extent cortical pathways show significant weight differences and whether these differences are consistent across animals (thereby comprising robust connectivity profiles) is an important and unresolved neuroanatomical issue. Here we report a quantitative retrograde tracer analysis in the cynomolgus macaque monkey of the weight consistency of the afferents of cortical areas across brains via calculation of a weight index (fraction of labeled neurons, FLN). Injection in 8 cortical areas (3 occipital plus 5 in the other lobes) revealed a consistent pattern: small subcortical input (1.

Derivation and cloning of a novel rhesus embryonic stem cell line stably expressing tau-green fluorescent protein.

Embryonic stem cells (ESC) have the ability of indefinite self-renewal and multilineage differentiation, and they carry great potential in cell-based therapies. The rhesus macaque is the most relevant preclinical model for assessing the benefit, safety, and efficacy of ESC-based transplantations in the treatment of neurodegenerative diseases. In the case of neural cell grafting, tracing both the neurons and their axonal projections in vivo is essential for studying the integration of the grafted cells in the host brain.

The concerted modulation of proliferation and migration contributes to the specification of the cytoarchitecture and dimensions of cortical areas.

Regionalization of cell cycle kinetics of cortical precursors has been described in nonhuman primates and rodents indicating a fate map of areas as distinct proliferative programs in the germinal zones of the neocortex. It remains to be understood how proliferative gradients during corticogenesis are transcribed into a stepwise function to form adult areal borders. Here we have used the monkey areas 17 and 18, which show striking cytoarchitectonic differences, as a model system for studying how developmental events establish areal boundaries in the adult.

G1 phase regulation, area-specific cell cycle control, and cytoarchitectonics in the primate cortex.

We have investigated the cell cycle-related mechanisms that lead to the emergence of primate areas 17 and 18. These areas are characterized by striking differences in cytoarchitectonics and neuron number. We show in vivo that (1) area 17 precursors of supragranular neurons exhibit a shorter cell cycle duration, a reduced G1 phase, and a higher rate of cell cycle reentry than area 18 precursors; (2) area 17 and area 18 precursors show contrasting and specific levels of expression of cyclin E (high in area 17, low in area 18) and p27Kip1 (low in area 17, high in area 18); (3) ex vivo up- and downmodulation of cyclin E and p27Kip1 show that both regulators influence cell cycle kinetics by modifying rates of cell cycle progression and cell cycle reentry; (4) modeling the areal differences in cell cycle parameters suggests that they contribute to areal differences in numbers of precursors and neuron production.

Early specification of the hierarchical organization of visual cortical areas in the macaque monkey.

The laminar organization of cortico-cortical projection neurons (expressed by the percentage of supragranular projecting neurons - SLN%) characterizes cortical pathways as feedforward (FF) or feedback (FB) and determines the hierarchical ranking of cortical areas. There is evidence of a developmental reduction in SLN% of pathways to area V1. Here, by analyzing pre- and postnatal projections to area V4, we have been able to address whether developmental reductions of SLN% impact on information processing in the immature cortex.

Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey.

We examined the development of the occipital lobe in fetal monkeys between embryonic day 37 (E37) and E108 in Nissl-stained and acetylcholine esterase (AChE)-reacted sections. We paid particular attention to features that distinguish the development of presumptive area 17. At E46 the neuroepithelium consists of a ventricular zone and a monolayer cortical plate sandwiched between a thin marginal zone and a minimal presubplate.

Phenotypic characterisation of respecified visual cortex subsequent to prenatal enucleation in the monkey: development of acetylcholinesterase and cytochrome oxidase patterns.

Prenatal bilateral enucleation induces cortex, which normally would have become striate cortex, to follow a default developmental pathway and to take on the cytoarchitectonic appearance of extrastriate cortex (default extrastriate cortex, Dehay et al. [1996] J. Comp.

Contribution of thalamic input to the specification of cytoarchitectonic cortical fields in the primate: effects of bilateral enucleation in the fetal monkey on the boundaries, dimensions, and gyrification of striate and extrastriate cortex.

Bilateral enucleation was performed at different fetal ages during corticogenesis, and the brains were prepared for histological examination. Early-enucleated fetuses (operated prior to embryonic day 77) showed morphological changes at the level of the thalamus and the cortex. In the thalamus, there was a loss of lamination and a decrease in size of the lateral geniculate nucleus.

Modulation of the cell cycle contributes to the parcellation of the primate visual cortex.

An as-yet unresolved issue in developmental neurobiology is whether the discrete areas that form the mammalian cortex emerge from a uniform cortical plate or whether they are already specified in the germinal zone. A feature of the primate striate cortex is that the number of neurons per unit area is twice that of anywhere else in the cerebral cortex. Here we take advantage of this unique structural feature to investigate whether the extra striate cortical cells are due to increased neuron production during neurogenesis.

Visuomotor properties of neurons of the anterior suprasylvian gyrus in the awake cat.

Single cell activity was recorded from the Anterior Suprasylvian (ASS) gyrus of cats trained to orient their gaze toward visual or auditory stimuli. Sixty-five fixation cells were activated or suppressed as long as the animals were attentive to a particular region of space in the tangential or in the radial direction. Most of these fixation cells were neither light nor sound sensitive.