Loss of Dicer in Newborn Melanocytes Leads to Premature Hair Graying and Changes in Integrin Expression.

Premature hair graying occurs owing to the depletion of melanocyte stem cells in the hair follicle, which can be accelerated by stress caused by genetic or environmental factors. However, the connection between stress and melanocyte stem cell loss is not fully understood. MicroRNAs are molecules that control gene expression by regulating mRNA stability and translation and are produced by the enzyme Dicer, which is repressed under stress.

Guidelines on human factors in critical situations 2023.

Objective: To provide guidelines to define the place of human factors in the management of critical situations in anaesthesia and critical care.

Design: A committee of nineteen experts from the SFAR and GFHS learned societies was set up. A policy of declaration of links of interest was applied and respected throughout the guideline-producing process.

Derivation and Use of Cell Lines from Mouse Models of Melanoma.

The establishment of consistent genetically modified mouse melanoma models and cell lines is of paramount importance for prevention and treatment. In this study, we review the different mouse melanoma cell lines that have been established. After careful molecular characterization of the established mouse melanoma cell lines, modification of the genome, microenvironment, or even the environment using appropriate in cellulo and in vivo assays may reveal novel genetic and nongenetic changes.

Electronic transport through single-molecule oligophenyl-diethynyl junctions with direct gold-carbon bonds formed at low temperature.

We report on the first systematic transport study of alkynyl-ended oligophenyl-diethynyl (OPA) single-molecule junctions with direct Au-C anchoring scheme at low temperature using the mechanically controlled break junction technique. Through quantitative statistical analysis of opening traces, conductance histograms and density functional theory studies, we identified different types of junctions, classified by their conductance and stretching behavior, for OPA molecules between Au electrodes with two to four phenyl rings. We performed inelastic electron tunneling spectroscopy and observed the excitation of Au-C vibrational modes confirming the existence of Au-C bonds at low temperature and compared the stability of molecule junctions upon mechanical stretching.

Activating Silent Glycolysis Bypasses in .

All living organisms share similar reactions within their central metabolism to provide precursors for all essential building blocks and reducing power. To identify whether alternative metabolic routes of glycolysis can operate in , we complementarily employed design, rational engineering, and adaptive laboratory evolution. First, we used a genome-scale model and identified two potential pathways within the metabolic network of this organism replacing canonical Embden-Meyerhof-Parnas (EMP) glycolysis to convert phosphosugars into organic acids.

Genetic and biocatalytic basis of formate dependent growth of Escherichia coli strains evolved in continuous culture.

The reductive glycine pathway was described as the most energetically favorable synthetic route of aerobic formate assimilation. Here we report the successful implementation of formatotrophy in Escherichia coli by means of a stepwise adaptive evolution strategy. Medium swap and turbidostat regimes of continuous culture were applied to force the channeling of carbon flux through the synthetic pathway to pyruvate establishing growth on formate and CO as sole carbon sources.

Impact of Intermolecular Non-Covalent Interactions in a Cu Pd Discrete Assembly: Conformers' Geometries and Stimuli-Sensitive Luminescence Properties.

A new highly solid-state luminescent phase of a previously reported weakly luminescent Cu Pd dicationic assembly is reported revealing the high geometrical versatility of this moiety that importantly alters its luminescent properties. This very minor new species B is based on a different conformer scaffold than the one encountered in the previously reported B form and, essentially differs from B by displaying shorter Cu -Cu intermetallic distances. DFT calculations allow concluding that the predominance in the solid-state of the weakly luminescent and less stable B phase is due to the extra stability induced by a larger number of intermolecular non-covalent π-CH interactions in its crystalline packing and not by the intrinsic stability of the Cu Pd dicationic moiety.

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma.

G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established.

Adipocyte Extracellular Vesicles Decrease p16 in Melanoma: An Additional Link between Obesity and Cancer.

Obesity is a recognized factor for increased risk and poor prognosis of many cancers, including melanoma. In this study, using genetically engineered mouse models of melanoma (Nras transgenic expression, associated or not with Cdkn2a heterozygous deletion), we show that obesity increases melanoma initiation and progression by supporting tumor growth and metastasis, thereby reducing survival. This effect is associated with a decrease in p16 expression in tumors.

Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage.

The canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates transcription of Mitf-M, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, whereas the second wave of melanocytes is derived from Schwann cell precursors (SCPs).

BRN2 is a non-canonical melanoma tumor-suppressor.

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a Braf Pten context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis.

Efficacy of Targeted Radionuclide Therapy Using [I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma.

Purpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance.

Methods: For TRT, we used a melanin radiotracer ([I]ICF01012) currently in phase 1 clinical trial (NCT03784625). TRT alone or combined with MEKi was evaluated in three-dimensional melanoma spheroid models of human BRAF SK-MEL-3, murine NRAS 1007, and WT B16F10 melanomas.

Three-dimensional reconstruction of the upper limb from anatomical slices of the Korean visible human: simulation and educational application.

Purpose: Digital anatomy is a novel emerging discipline. Use of virtual reality brings a revolution in educational anatomy by improving retention and learning outcomes. Indeed, virtual dissection is a new learning tool for students and surgeons.

Genetic Analysis of sp.86 Reveals Involvement of Corrinoids in Chlordecone and Lindane Biotransformations.

Chlordecone (Kepone®) and γ-hexachlorocyclohexane (γ-HCH or lindane) have been used for decades in the French West Indies (FWI) resulting in long-term soil and water pollution. In a previous work, we have identified a new species (sp.86) that is able to transform chlordecone into numerous products under anaerobic conditions.

On the reliability of acquiring molecular junction parameters by Lorentzian fitting of / curves.

Fitting the I/V curves of molecular junctions by simple analytical models is often done to extract relevant molecular parameters such as energy level alignment or interfacial electronic coupling to build up useful property-relationships. However, such models can suffer from severe limitations and hence provide unreliable molecular parameters. This is illustrated here by extracting key molecular parameters by fitting computed voltage-dependent transmission spectra and by comparing them to the values obtained by fitting the calculated I/V curves with a typical Lorentzian model used in the literature.

Descriptive anatomy of the inferior epigastric, subscapular and internal thoracic vascular pedicles in three domestic mammals: A comparative study.

The descriptive anatomy of the inferior epigastric, subscapular and internal thoracic vascular pedicles of domestic animals is not fully known. Improvement of our knowledge in this field could lead to better development of animal models for both pedagogical purposes and surgical experimentation. The objective of this comparative study was to describe the descriptive anatomy of the inferior epigastric, subscapular and internal thoracic pedicles in three domestic mammals commonly used as animal models for experimentation.

Anatomy of the axillary arch: from its incidence in human to an embryologic and a phylogenetic explanation of its origins.

Introduction: Typically, the axillary arch is defined as a fleshy slip running from latissimus dorsi to the anterior aspect of the humerus. Phylogeny seems to give the most relevant and plausible explanation of this anatomical variant as a remnant of the panniculus carnosus. However, authors are not unanimous about its origin.

LKB1 specifies neural crest cell fates through pyruvate-alanine cycling.

Metabolic processes underlying the development of the neural crest, an embryonic population of multipotent migratory cells, are poorly understood. Here, we report that conditional ablation of the tumor suppressor kinase in mouse neural crest stem cells led to intestinal pseudo-obstruction and hind limb paralysis. This phenotype originated from a postnatal degeneration of the enteric nervous ganglia and from a defective differentiation of Schwann cells.

Continuous Culture Adaptation of AM1 and TK 0001 to Very High Methanol Concentrations.

The bio-economy relies on microbial strains optimized for efficient large scale production of chemicals and fuels from inexpensive and renewable feedstocks under industrial conditions. The reduced one carbon compound methanol, whose production does not involve carbohydrates needed for the feed and food sector, can be used as sole carbon and energy source by methylotrophic bacteria like AM1. This strain has already been engineered to produce various commodity and high value chemicals from methanol.

C57BL/6 congenic mouse NRAS melanoma cell lines are highly sensitive to the combination of Mek and Akt inhibitors in vitro and in vivo.

RAS is frequently mutated in various tumors and known to be difficult to target. NRAS are the second most frequent mutations found in human skin melanoma after BRAF . Aside from surgery, various approaches, including targeted therapies, immunotherapies, and combination therapies, are used to treat patients carrying NRAS mutations, but they are inefficient.

Assessing pain in critically ill brain-injured patients: a psychometric comparison of 3 pain scales and videopupillometry.

Three clinical scales (the Nociception Coma Scale adapted for Intubated patients [NCS-I], its Revised version [NCS-R-I], and the Behavioral Pain Scale [BPS]) and videopupillometry were compared for measuring pain in intubated, noncommunicating, critically ill, brain-injured patients. Pain assessment was performed before, during, just after, and 5 minutes after 3 procedures: the reference non-nociceptive procedure (assessment of the Richmond Agitation Sedation Scale) and 2 nociceptive procedures (turning and tracheal suctioning). The primary endpoint was construct validity (discriminant and criterion validation), determined by comparing pain measurements between different times/procedures.

Anatomical variations of the subscapular pedicle and its terminal branches: an anatomical study and a reappraisal in the light of current surgical approaches.

Purpose: While anatomical variations of the subscapular vessels are frequently encountered during axillary dissection, little is found in the literature. The aim of this cadaveric study was to define arterial and venous anatomical variations and frequencies of the subscapular vascular pedicle and its terminal/afferent vessels in women.

Methods: We performed 80 dissections of the axillary region on forty female formalin-embalmed cadavers.

Molecular and cellular basis of depigmentation in vitiligo patients.

Vitiligo is a chronic skin disease characterized by the appearance of zones of depigmentation. It is mostly described as an autoimmune disease in which the immune system destroys the melanocytes. Consistent with this origin, genetic studies have implicated genes encoding proteins mediating the immune response targeting melanocytes in the aetiology of this disease, together with proteins specific to these cells.

Three-Dimensional Modelization of the Female Human Inferior Hypogastric Plexus: Implications for Nerve-Sparing Radical Hysterectomy.

Background/aims: This study aims to describe the autonomic nervous network of the female pelvis with a 3D model and to provide a safe plane of dissection during radical hysterectomy for cervical cancer.

Methods: Pelvises of 3 human female fetuses were studied by using the computer-assisted anatomic dissection.

Results: The superior hypogastric plexus (SHP) was located at the level of the aortic bifurcation in front of the sacral promontory and divided inferiorly and laterally into 2 hypogastric nerves (HN).