Identification of miR-141 as a Regulator of Epidermal Homeostasis.

MicroRNAs, small endogenous noncoding RNAs, are involved in the regulation of epidermal homeostasis. Among them, miR-203 was the most described and expressed in human epidermis, promoting keratinocyte (KC) differentiation by repressing genes involved in proliferation. To identify other microRNAs involved in this process, the miRNomes of normal human KCs cultured in monolayer (2-dimensional) or in 3-dimensional reconstructed skin were compared.

A Computational Framework for Memory Engrams.

Memory engrams in mice brains are potentially related to groups of concept cells in human brains. A single concept cell in human hippocampus responds, for example, not only to different images of the same object or person but also to its name written down in characters. Importantly, a single mental concept (object or person) is represented by several concept cells and each concept cell can respond to more than one concept.

A dynamic attractor network model of memory formation, reinforcement and forgetting.

Empirical evidence shows that memories that are frequently revisited are easy to recall, and that familiar items involve larger hippocampal representations than less familiar ones. In line with these observations, here we develop a modelling approach to provide a mechanistic understanding of how hippocampal neural assemblies evolve differently, depending on the frequency of presentation of the stimuli. For this, we added an online Hebbian learning rule, background firing activity, neural adaptation and heterosynaptic plasticity to a rate attractor network model, thus creating dynamic memory representations that can persist, increase or fade according to the frequency of presentation of the corresponding memory patterns.

Identification and functional validation of SRC and RAPGEF1 as new direct targets of miR-203, involved in regulation of epidermal homeostasis.

The epidermis is mostly composed of keratinocytes and forms a protecting barrier against external aggressions and dehydration. Epidermal homeostasis is maintained by a fine-tuned balance between keratinocyte proliferation and differentiation. In the regulation of this process, the keratinocyte-specific miR-203 microRNA is of the outmost importance as it promotes differentiation, notably by directly targeting and down-regulating mRNA expression of genes involved in keratinocyte proliferation, such as ΔNp63, Skp2 and Msi2.

Oligonucleotide Enhancing Compound Increases Tricyclo-DNA Mediated Exon-Skipping Efficacy in the Mdx Mouse Model.

Nucleic acid-based therapeutics hold great promise for the treatment of numerous diseases, including neuromuscular disorders, such as Duchenne muscular dystrophy (DMD). Some antisense oligonucleotide (ASO) drugs have already been approved by the US FDA for DMD, but the potential of this therapy is still limited by several challenges, including the poor distribution of ASOs to target tissues, but also the entrapment of ASO in the endosomal compartment. Endosomal escape is a well recognized limitation that prevents ASO from reaching their target pre-mRNA in the nucleus.

Reliability of Morphological and PCR Methods for the Official Diagnosis of (Coleoptera: Nitidulidae): A European Inter-Laboratory Comparison.

The Small Hive Beetle ( Murray, 1867) is an invasive scavenger of honeybees. Originally endemic in sub-Saharan Africa, it is regulated internationally in order to preserve the areas still free from this species. To ensure the reliability of official diagnoses in case of introduction, an inter-laboratory comparison was organised on the identification of by morphology and real-time PCR.

When shared concept cells support associations: Theory of overlapping memory engrams.

Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks.

Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides.

Tricyclo-DNA (tcDNA) is a conformationally constrained oligonucleotide analog that has demonstrated great therapeutic potential as antisense oligonucleotide (ASO) for several diseases. Like most ASOs in clinical development, tcDNA were modified with phosphorothioate (PS) backbone for therapeutic purposes in order to improve their biodistribution by enhancing association with plasma and cell protein. Despite the advantageous protein binding properties, systemic delivery of PS-ASO remains limited and PS modifications can result in dose limiting toxicities in the clinic.

Evaluation of drug deliveries and refunds for obstructive airway diseases in France between 2012 and 2017.

Background: The aim of this survey was to investigate variations of drugs for obstructive airway diseases delivery rates and refunds at a national level which are rarely reported.

Methods: The French national health data system (56 million, 87% of the population) was used to identify insurance beneficiaries with at least one drug delivery (Anatomical Therapeutic Classification R03) per year between 2012 and 2017.

Results: At least one drug delivery in 2017 was identified for 7.

Characteristics of people with severe hypertension in France and determinants of medication persistence after 6 years.

Background: Low medication persistence is reported in patients with severe hypertension but few data are available according to drug classes.

Method: Adults without cardiovascular disease who started treatment, in a semester between 2010 and 2012, with two concurrent dispensings of at least three classes were identified in the French national health data system. High persistence after 12 semesters of follow-up was defined by a 6-monthly mean of number of drug classes equal to or greater than 80%.

An international inter-laboratory study on Nosema spp. spore detection and quantification through microscopic examination of crushed honey bee abdomens.

Nosemosis is a microsporidian disease causing mortality and weakening of honey bee colonies, especially in the event of co-exposure to other sources of stress. As a result, the disease is regulated in some countries. Reliable and harmonised diagnosis is crucial to ensure the quality of surveillance and research results.

Long-Term Efficacy of AAV9-U7snRNA-Mediated Exon 51 Skipping in Mice.

Gene therapy and antisense approaches hold promise for the treatment of Duchenne muscular dystrophy (DMD). The advantages of both therapeutic strategies can be combined by vectorizing antisense sequences into an adeno-associated virus (AAV) vector. We previously reported the efficacy of AAV-U7 small nuclear RNA (U7snRNA)-mediated exon skipping in the mouse, the mouse, and the golden retriever muscular dystrophy (GRMD) dog model.

Thulium-laser retrograde intra renal ablation of upper urinary tract transitional cell carcinoma: an ESUT Study.

Background: Radical nephroureterectomy (RNU) is the gold standard treatment for upper urinary tract urothelial carcinoma (UTUC); however, patients presenting with small low-grade UTUC have been treated by flexible ureteroscopic laser ablation with good outcomes. Different types of laser have been discussed in the literature including Holmium and Neodymium lasers. We aimed to assess the safety and efficacy of Thulium laser (Tm:YAG) in the ureteroscopic ablation of UTUC.

Optimal Stimulation Protocol in a Bistable Synaptic Consolidation Model.

Synaptic changes induced by neural activity need to be consolidated to maintain memory over a timescale of hours. In experiments, synaptic consolidation can be induced by repeating a stimulation protocol several times and the effectiveness of consolidation depends crucially on the repetition frequency of the stimulations. We address the question: is there an understandable reason why induction protocols with repetitions at some frequency work better than sustained protocols-even though the accumulated stimulation strength might be exactly the same in both cases? In real synapses, plasticity occurs on multiple time scales from seconds (induction), to several minutes (early phase of long-term potentiation) to hours and days (late phase of synaptic consolidation).

miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma.

Incidence of cutaneous squamous cell carcinomas (cSCCs) constantly increases in the Caucasian population. Developing preferentially on precancerous lesions such as actinic keratoses due to chronic sunlight exposure, cSCCs result from the malignant transformation of keratinocytes. Although a resection of the primary tumor is usually curative, a subset of aggressive cSCCs shows a high risk of recurrence and metastases.

CDC25A targeting by miR-483-3p decreases CCND-CDK4/6 assembly and contributes to cell cycle arrest.

Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle, which then stops when confluence is reached again. Although the events involved in cell cycle entry have been widely documented, those managing cell cycle exit have remained so far ill defined. We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p, which acts as a mandatory signal triggering cell cycle arrest when confluence is reached.

The role of the elastography in the diagnosis of prostate cancer: a retrospective study on 460 patients.

Objective: Prostate cancer is one of the most common cancer among men in industrialized total Prostatic Specific Antigen (PSA) and PSA ratio, Trans Rectal Ultrasound Scan (TRUS) and prostate biopsy, which is the gold standard for tumoral diagnosis. The poor sensibility of TRUS, when DRE and/or PSA are abnormal, requires prostate biopsy for diagnostic confirmation. The aim of this study was to evaluate the sensibility and the specificity of real time elastography (SE) with and without the association of TRUS for cancer diagnosis.

The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death.

Bcl-2 family members are key modulators of apoptosis that have recently been shown to also regulate autophagy. It has been previously reported that Bcl-2 and Bcl-X(L) bind and inhibit BECN1, an essential mediator of autophagy. Bcl-B is an anti-apoptotic member of the Bcl-2 family that possesses the four BH (Bcl-2 homology) domains (BH1, BH2, BH3 and BH4) and a predicted C-terminal trans-membrane domain.

miR-483-3p controls proliferation in wounded epithelial cells.

The mechanisms that regulate keratinocyte migration and proliferation in wound healing remain largely unraveled, notably regarding possible involvements of microRNAs (miRNAs). Here we disclose up-regulation of miR-483-3p in 2 distinct models of wound healing: scratch-injured cultures of human keratinocytes and wounded skin in mice. miR-483-3p accumulation peaks at the final stage of the wound closure process, consistent with a role in the arrest of "healing" progression.

[Real-time elastography in the diagnosis of prostate cancer: personal experience].

Introduction: Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. The indication to perform a prostate biopsy is digital rectal examination suspicious for prostate cancer, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity, and an evidence of hypoechoic area at transrectal ultrasound scan.

Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus.

Bluetongue virus causes an emerging disease of ruminants, principally affecting sheep and cattle. Since 1998, there have been multiple separate outbreaks of bluetongue disease in Europe that have highlighted the need for a safe, efficacious, DIVA compliant vaccine. We report here a new baculovirus expression strategy which allowed pre-integration of the genes encoding the BTV inner capsid proteins at one baculovirus locus and those encoding the outer capsid proteins at a different locus.

Primary malignant melanoma of the bladder.

Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder.

Nurses' observational study on the practice of secondary prevention in a cardiovascular department.

Background: Although interventional studies have established the prognostic importance of the control of risk factors in patients with cardiovascular disease, reviews invariably show that the implementation of secondary prevention in patients with cardiovascular disease during hospitalization for acute manifestations or interventions is unsatisfactory. The aim of this study was to observe secondary prevention practice in a cardiovascular department, as part of a quality assurance program.

Methods: Two hundred and twenty patients discharged from the intensive coronary care unit, cardiac surgery unit and vascular surgery unit were prospectively included.