Uninterrupted in vivo cerebral microdialysis measures of the acute neurochemical response to a single or repeated concussion in a rat model combining force and rotation.

Altered extracellular amino acid concentrations following concussion or mild traumatic brain injury can result in delayed neuronal damage through overactivation of NMDA glutamatergic receptors. However, the consequences of repeated concussions prior to complete recovery are not well understood. In this study, we utilized in vivo cerebral microdialysis and a weight-drop model to investigate the acute neurochemical response to single and repeated concussions in adult rats that were fully conscious.

Cancer Cell Biomechanical Properties Accompany Tspan8-Dependent Cutaneous Melanoma Invasion.

The intrinsic biomechanical properties of cancer cells remain poorly understood. To decipher whether cell stiffness modulation could increase melanoma cells' invasive capacity, we performed both in vitro and in vivo experiments exploring cell stiffness by atomic force microscopy (AFM). We correlated stiffness properties with cell morphology adaptation and the molecular mechanisms underlying epithelial-to-mesenchymal (EMT)-like phenotype switching.

Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice.

In Parkinson's disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to be sustained through a diffuse basal tone of DA; but experimental evidence for this is limited. Here we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKO mice) abrogates most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact.

Efficacy of prophylactic versus therapeutic administration of the NMDA receptor antagonist MK-801 on the acute neurochemical response to a concussion in a rat model combining force and rotation.

Objective: Alterations in amino acid concentrations are a major contributor to the persistent neurological and behavioral effects induced by concussions and mild traumatic brain injuries (TBIs). Glutamate, the most abundant excitatory amino acid in the CNS, has a major role in the pathophysiological process of concussion. The indiscriminate liberation of glutamate immediately after a concussion triggers an excitotoxic response that leads to cell death, neuronal damage, and the dysfunction of surviving neurons, largely by overactivation of N-methyl-d-aspartate (NMDA) glutamatergic receptors.

RASGRF2 gene fusions identified in a variety of melanocytic lesions with distinct morphological features.

The WHO classification identifies nine classes of melanocytic proliferations according to location, UV exposure, histological, and genetic features. Only a minority of lesions remain unclassified. We describe five cases that harbored either an ERBIN-RASGRF2 or an ATP2B4-RASGRF2 in-frame fusion transcript.

Biomechanical Properties of Cancer Cells.

Since the crucial role of the microenvironment has been highlighted, many studies have been focused on the role of biomechanics in cancer cell growth and the invasion of the surrounding environment. Despite the search in recent years for molecular biomarkers to try to classify and stratify cancers, much effort needs to be made to take account of morphological and nanomechanical parameters that could provide supplementary information concerning tissue complexity adaptation during cancer development. The biomechanical properties of cancer cells and their surrounding extracellular matrix have actually been proposed as promising biomarkers for cancer diagnosis and prognosis.

Stiffness measurement is a biomarker of skin ageing in vivo.

Human skin is particularly vulnerable to age-related deterioration and undergoes profound structural and functional changes, reflected in the external skin appearance. Skin ageing is characterized by features such as wrinkling or loss of elasticity. Even if research advances have been done concerning the molecular mechanisms that underlie these changes, very few studies have been conducted concerning the structure stiffness of the skin organ as a whole.

Tspan8 Drives Melanoma Dermal Invasion by Promoting ProMMP-9 Activation and Basement Membrane Proteolysis in a Keratinocyte-Dependent Manner.

Melanoma is the most aggressive skin cancer with an extremely challenging therapy. The dermal-epidermal junction (DEJ) degradation and subsequent dermal invasion are the earliest steps of melanoma dissemination, but the mechanisms remain elusive. We previously identified Tspan8 as a key actor in melanoma invasiveness.

Melanocytic tumors with MAP3K8 fusions: report of 33 cases with morphological-genetic correlations.

We report a series of 33 skin tumors harboring a gene fusion of the MAP3K8 gene, which encodes a serine/threonine kinase. The MAP3K8 fusions were identified by RNA sequencing in 28 cases and by break-apart FISH in five cases. Cases in which fusion genes were fully characterized demonstrated a fusion of the 5' part of MAP3K8 comprising exons 1-8 in frame to one of several partner genes at the 3' end.

A Novel and Translational Rat Model of Concussion Combining Force and Rotation with In Vivo Cerebral Microdialysis.

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal.

Tspan8-β-catenin positive feedback loop promotes melanoma invasion.

Due to its high proclivity to metastasize, and despite the recent development of targeted and immune therapy strategies, melanoma is still the deadliest form of skin cancer. Therefore, understanding the molecular mechanisms underlying melanoma invasion remains crucial. We previously characterized Tspan8 for its ability to prompt melanoma cell detachment from their microenvironment and trigger melanoma cell invasiveness, but the signaling events by which Tspan8 regulates the invasion process still remain unknown.

A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion.

This corrects the article DOI: 10.1038/onc.2016.

p53 targets TSPAN8 to prevent invasion in melanoma cells.

Cutaneous melanoma is a very deadly cancer because of its proclivity to metastasize. Despite the recent development of targeted and immune therapies, patient survival remains low. It is therefore crucial to enhance understanding of the molecular mechanisms underlying invasion.

Tetraspanin 8 is a novel regulator of ILK-driven β1 integrin adhesion and signaling in invasive melanoma cells.

Melanoma is well known for its propensity for lethal metastasis and resistance to most current therapies. Tumor progression and drug resistance depend to a large extent on the interplay between tumor cells and the surrounding matrix. We previously identified Tetraspanin 8 (Tspan8) as a critical mediator of melanoma invasion, whose expression is absent in healthy skin.

Asymmetric Direct Reciprocal Connections Between Primary Visual and Somatosensory Cortices of the Mouse.

Several studies show direct connections between primary sensory cortices involved in multisensory integration. The purpose of this study is to understand the microcircuitry of the reciprocal connections between visual and somatosensory cortices. The laminar distribution of retrogradely labeled cell bodies in V1 and in the somatosensory cortex both in (S1BF) and outside (S1) the barrel field was studied to provide layer indices in order to determine whether the connections are of feedforward, feedback or lateral type.

A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion.

Melanoma is the deadliest form of skin cancer owing to its proclivity to metastasise, and recently developed therapies have not yielded the expected results, because almost all patients relapse. Therefore, understanding the molecular mechanisms that underlie early invasion by melanoma cells is crucial to improving patient survival. We have previously shown that, whereas the Tetraspanin 8 protein (Tspan8) is undetectable in normal skin and benign lesions, its expression arises with the progression of melanoma and is sufficient to increase cell invasiveness.

MicroRNA-23b-3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF-ß-SMAD2 signalling pathway.

MicroRNAs (miRNAs) are a class of short non-coding RNAs capable of repressing gene expression at the post-transcriptional level. miRNAs participate in the control of numerous cellular mechanisms, including skin homeostasis and epidermal differentiation. However, few miRNAs involved in these processes have been identified so far in human skin, and the gene networks they control remain largely unknown.

[Tetraspanins in cutaneous physiopathology].

Tetraspanins are transmembrane proteins that interact laterally with each other and with different partners such as integrins, immunoglobulin (Ig)-domain-containing proteins, growth factors and cytokine receptors. Such tetraspanin-partner complexes help to organize dynamic membrane networks called "tetraspanin web", which trigger different signalling pathways. Despite the fact that tetraspanins seem abundantly and widely expressed, their function remained unclear.

Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis.

Introduction: Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors.

Methods: IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively.

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex.

Effects of the PPAR-α agonist fenofibrate on acute and short-term consequences of brain ischemia.

In stroke, there is an imperative need to develop disease-modifying drugs able to (1) induce neuroprotection and vasculoprotection, (2) modulate recovery and brain plasticity, and (3) limit the short-term motor and cognitive consequences. We hypothesized that fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, could exert a beneficial effect on immediate and short-term poststroke consequences related to its pleiotropic mechanisms. Rats or mice were subjected to focal ischemia to determine the effects of acute treatment by fenofibrate on (i) motor and memory impairment, (2) both cerebral and vascular compartments, (3) inflammation, (4) neurogenesis, and (5) amyloid cascade.

GATA3 inhibits proliferation and induces expression of both early and late differentiation markers in keratinocytes of the human epidermis.

GATA3 belongs to the GATA transcription factor family and is a crucial regulator of lymphocyte differentiation. More recently, GATA3 was shown to be involved in skin cell lineage determination, in morphogenesis and maintenance of hair follicle keratinocytes as well as in epidermal barrier formation in mouse. In human, the potential role of GATA3 in the regulation of interfollicular epidermal homeostasis was still poorly explored.

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes.

The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes.