Stratum corneum nanotexture feature detection using deep learning and spatial analysis: a noninvasive tool for skin barrier assessment.

Background: Corneocyte surface nanoscale topography (nanotexture) has recently emerged as a potential biomarker for inflammatory skin diseases, such as atopic dermatitis (AD). This assessment method involves quantifying circular nano-size objects (CNOs) in corneocyte nanotexture images, enabling noninvasive analysis via stratum corneum (SC) tape stripping. Current approaches for identifying CNOs rely on computer vision techniques with specific geometric criteria, resulting in inaccuracies due to the susceptibility of nano-imaging techniques to environmental noise and structural occlusion on the corneocyte.

LYP regulates SLP76 and other adaptor proteins in T cells.

Background: The LYP tyrosine phosphatase presents a SNP (1858C > T) that increases the risk of developing autoimmune diseases such as type I diabetes and arthritis. It remains unclear how this SNP affects LYP function and promotes the development of these diseases. The scarce information about LYP substrates is in part responsible for the poor understanding of LYP function.

A Cross-Sectional Study to Assess the Knowledge of Pharmacy Students About Drug Pollution in Spain.

Unlabelled: The presence of pharmaceuticals in the environment is an issue of growing concern. The European Commission adopted the "European Union Strategic Approach to Pharmaceuticals in the Environment", which focuses on actions to reduce the risk of pharmaceuticals in the environment, including how environmental aspects can become part of medical training programs.

Objective: Obtain data from pharmacy students about pharmaceutical pollution to provide information about the training needs that may help develop new actions related to the training and dissemination of this issue.

Skin Barrier- and Immune Response-Related Biomarkers of Solar UVR Exposure Comparing Indoor and Outdoor Workers.

Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers.

Aberrant TIMP-1 production in tumor-associated fibroblasts drives the selective benefits of nintedanib in lung adenocarcinoma.

The fibrotic tumor microenvironment is a pivotal therapeutic target. Nintedanib, a clinically approved multikinase antifibrotic inhibitor, is effective against lung adenocarcinoma (ADC) but not squamous cell carcinoma (SCC). Previous studies have implicated the secretome of tumor-associated fibroblasts (TAFs) in the selective effects of nintedanib in ADC, but the driving factor(s) remained unidentified.

miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs.

The Role of Aryl Hydrocarbon Receptor in the Endothelium: A Systematic Review.

Activation of the aryl hydrocarbon receptor (AhR) has been shown to be important in physiological processes other than detoxification, including vascular homeostasis. Although AhR is highly expressed in the endothelium, its function has been poorly studied. This systematic review aims to summarise current knowledge on the AhR role in the endothelium and its cardiovascular implications.

Pathogen-specific structural features of Ras1 activation complex: uncovering new antifungal drug targets.

An important feature associated with pathogenicity is its ability to switch between yeast and hyphal forms, a process in which CaRas1 plays a key role. CaRas1 is activated by the guanine nucleotide exchange factor (GEF) CaCdc25, triggering hyphal growth-related signaling pathways through its conserved GTP-binding (G)-domain. An important function in hyphal growth has also been proposed for the long hypervariable region downstream the G-domain, whose unusual content of polyglutamine stretches and Q/N repeats make CaRas1 unique within Ras proteins.

Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.

Background: C3G is a guanine nucleotide exchange factor (GEF) that activates Rap1 to promote cell adhesion. Resting C3G is autoinhibited and the GEF activity is released by stimuli that signal through tyrosine kinases. C3G is activated by tyrosine phosphorylation and interaction with Crk adaptor proteins, whose expression is elevated in multiple human cancers.

Fetal and neonatal alloimmune thrombocytopenia: Current pathophysiological insights and perspectives for future diagnostics and treatment.

FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on integrin β3. The clinical effects range from no symptoms to fatal intracranial hemorrhage, but underlying pathophysiological determinants are poorly understood. Accumulating evidence suggests that differential antibody-Fc-glycosylation, activation of complement/effector cells, and integrin function-blocking effects contribute to clinical outcome.

Acute Sheehan's Syndrome Presenting with Hyponatremia Followed by a Spontaneous Pregnancy.

Background: Acute Sheehan's syndrome is rare, as well as hyponatremia as its initial manifestation. In addition, spontaneous pregnancy in patients after Sheehan's syndrome is unusual. To our knowledge, no cases of spontaneous pregnancy after acute Sheehan's syndrome have been reported.

Open-source controller for low-cost and high-speed atomic force microscopy imaging of skin corneocyte nanotextures.

High-speed atomic force microscopes (HS-AFMs) with high temporal resolution enable dynamic phenomena to be visualized at nanoscale resolution. However, HS-AFMs are more complex and costlier than conventional AFMs, and particulars of an open-source HS-AFM controller have not been published before. These high entry barriers hinder the popularization of HS-AFMs in both academic and industrial applications.

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play.

Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization, which have an impact on the biomechanical traits of the lung. In this context, the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is lost. Interestingly, several MMPs are overexpressed during PF and exhibit a clear profibrotic role (MMP-2, -3, -8, -11, -12 and -28), but a few are antifibrotic (MMP-19), have both profibrotic and antifibrotic capacity (MMP7), or execute an unclear (MMP-1, -9, -10, -13, -14) or unknown function.

Regulation of hemidesmosome dynamics and cell signaling by integrin α6β4.

Hemidesmosomes (HDs) are specialized multiprotein complexes that connect the keratin cytoskeleton of epithelial cells to the extracellular matrix (ECM). In the skin, these complexes provide stable adhesion of basal keratinocytes to the underlying basement membrane. Integrin α6β4 is a receptor for laminins and plays a vital role in mediating cell adhesion by initiating the assembly of HDs.

Information and Thermodynamics: Fast and Precise Approach to Landauer's Bound in an Underdamped Micromechanical Oscillator.

The Landauer principle states that at least k_{B}Tln2 of energy is required to erase a 1-bit memory, with k_{B}T the thermal energy of the system. We study the effects of inertia on this bound using as one-bit memory an underdamped micromechanical oscillator confined in a double-well potential created by a feedback loop. The potential barrier is precisely tunable in the few k_{B}T range.

EGFR-dependent tyrosine phosphorylation of integrin β4 is not required for downstream signaling events in cancer cell lines.

In epithelial cancers, the epidermal growth factor receptor (EGFR) and integrin α6β4 are frequently overexpressed and found to synergistically activate intracellular signaling pathways that promote cell proliferation and migration. In cancer cells, the β4 subunit is phosphorylated at tyrosine residues not normally recognized as kinase substrates; however, the function of these phosphotyrosine residues in cancer cells is a subject of much debate. In EGFR-overexpressing carcinoma cells, we found that the Src family kinase (SFK) inhibitor PP2 reduces β4 tyrosine phosphorylation following the activation of EGFR.

C3G self-regulatory mechanism revealed: implications for hematopoietic malignancies.

Abnormally increased signaling by the GTPase RAP1 favors progression of diverse tumors. We have characterized the auto-regulation and activation of C3G (RAPGEF1), an activator of RAP1. This led us to discover mutations in non-Hodgkin's lymphomas that activate C3G-RAP1 constitutively, suggesting that deregulation of C3G may favor the dissemination of tumor cells.

Excessive Maternal Weight and Diabetes Are Risk Factors for Macrosomia: A Cross-Sectional Study of 42,663 Pregnancies in Uruguay.

Objective: To evaluate the risk of macrosomia in newborns from women with gestational diabetes, pregestational diabetes, overweight, and obesity in Uruguay in 2012, as well as its association with prolonged pregnancy, maternal age, multiparity, and excessive gestational weight gain (EGWG).

Methods: We performed a cross-sectional study of 42,663 pregnant women. The risk of macrosomia was studied using logistic regression.

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair.

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear.

Experimental characterization and theoretical analysis of cell tip oscillations in directional solidification.

Experiments performed in DECLIC-DSI on board the International Space Station evidenced oscillatory modes during the directional solidification of a bulk sample of succinonitrile-based transparent alloy. The interferometric data acquired during a reference experiment, V_{p}=1 μm/s and G=19 K/cm, allowed us to reconstruct the cell shape and thus measure the cell tip position, radius, and growth velocity evolution, in order to quantify the dynamics of the oscillating cells. This study completes our previous reports [Bergeon et al.

Mechanisms of autoregulation of C3G, activator of the GTPase Rap1, and its catalytic deregulation in lymphomas.

C3G is a guanine nucleotide exchange factor (GEF) that regulates cell adhesion and migration by activating the GTPase Rap1. The GEF activity of C3G is stimulated by the adaptor proteins Crk and CrkL and by tyrosine phosphorylation. Here, we uncovered mechanisms of C3G autoinhibition and activation.

Analysis of gene variants in the GASH/Sal model of epilepsy.

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients.