uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells.

In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells.

Persistent effects of pre-Columbian plant domestication on Amazonian forest composition.

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant.

Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes.

Aims: Calmodulin (CaM) is a small protein, encoded by three genes (CALM1-3), exerting multiple Ca2+-dependent modulatory roles. A mutation (F142L) affecting only one of the six CALM alleles is associated with long QT syndrome (LQTS) characterized by recurrent cardiac arrests. This phenotypic severity is unexpected from the predicted allelic balance.

Late sodium current and intracellular ionic homeostasis in acute ischemia.

Blockade of the late Na current (I ) protects from ischemia/reperfusion damage; nevertheless, information on changes in I during acute ischemia and their effect on intracellular milieu is missing. I , cytosolic Na and Ca activities (Na, Ca) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I blockade. The results indicate that I was enhanced during ISC in spite of changes in action potential (AP) contour; I significantly contributed to Na rise, but only marginally to Ca rise.

Roles of Plasmablasts and B Cells in IgG4-Related Disease: Implications for Therapy and Early Treatment Outcomes.

High serum IgG4 concentrations are a striking feature of many patients with IgG4-related disease (IgG4-RD). Blood levels of IgG4 often reach ten, twenty, and even thirty or more times higher than the upper limit of normal. Under the proper clinical circumstances, the finding of an elevated serum IgG4 concentration serves as a useful biomarker for the diagnosis of this condition.

Identification of prevalent patients with epilepsy using administrative data: the Tuscany experience.

Overall prevalence of epilepsy ranges from 4 to 10 cases per 1000. Italy lacks recent epidemiological studies on large populations. In the present study, prevalence of epilepsy has been assessed in Tuscany, an Italian Region with 3,750,000 habitants, implementing an algorithm based on administrative data from the Regional Information Health System.

Mechanical Thrombectomy in Acute Ischemic Stroke: Initial Single-Center Experience and Comparison with Randomized Controlled Trials.

Background: Until recently, intravenous thrombolysis was the only reperfusion therapy with proven efficacy in patients with acute ischemic stroke. However, this treatment option has low recanalization rates in large-vessel occlusions. The search for additional treatments continued until 5 randomized trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT) revealed the superiority of mechanical thrombectomy for anterior circulation large-vessel occlusion.

Urokinase-type Plasminogen Activator (uPA) Binding to the uPA Receptor (uPAR) Promotes Axonal Regeneration in the Central Nervous System.

Axonal injury is a common cause of neurological dysfunction. Unfortunately, in contrast to axons from the peripheral nervous system, the limited capacity of regeneration of central nervous system (CNS) axons is a major obstacle for functional recovery in patients suffering neurological diseases that involve the subcortical white matter. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to the urokinase-type plasminogen activator receptor (uPAR) catalyzes the conversion of plasminogen into plasmin on the cell surface.

Tissue-type Plasminogen Activator (tPA) Modulates the Postsynaptic Response of Cerebral Cortical Neurons to the Presynaptic Release of Glutamate.

Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al.

Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing.

While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. The main objective of this study was to perform an unbiased, whole transcriptome search for genes that associate with intrinsic skin youthfulness. To accomplish this, healthy women (n = 122) of European descent, ages 18-89 years with Fitzpatrick skin type I/II were examined for facial skin aging parameters and clinical covariates, including smoking and ultraviolet exposure.

Tumor-tropic endothelial colony forming cells (ECFCs) loaded with near-infrared sensitive Au nanoparticles: A "cellular stove" approach to the photoablation of melanoma.

In the photothermal treatments (PTs) of tumor, the localization of a high number of near-infrared (NIR) absorbing gold nanoparticles in the tumor mass is still a challenging issue. Here, we propose a promising strategy to deliver therapeutic chitosan-coated gold nanoparticles to tumor cells as hidden cargo of Endothelial Colony Forming Cells (ECFCs) endowed with an innate tumor-tropism. Remarkably, ECFC gold enrichement doesn't affect cell viability and preserves the endothelial lineage characteristics such as capillary morphogenesis and cell migration.

"How I manage" IgG4-Related Disease.

IgG4-related disease (IgG4-RD) is an immune-mediated disease driven by interactions on several levels between cells of the B and T lineages. A key driver of IgG4-RD is believed to be a novel CD4+ cytotoxic T lymphocyte that bears SLAM-F7 on its surface. This cell is presumed to be sustained by continuous antigen presentation by cells of the B cell lineage, particularly plasmablasts.

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.

Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center.

Juxta-vertebral lesions in granulomatosis with polyangiitis.

Objectives: To describe the clinical, pathological, serological, and radiological characteristics of juxta-vertebral masses occurring in patients with granulomatosis with polyangiitis (GPA).

Methods: We analyzed the clinical records of patients with juxta-vertebral lesions from our GPA study cohort and reviewed the English literature for other cases of GPA with juxta-vertebral localization.

Results: Out of 74 patients in our GPA study cohort, six (8%) had juxta-vertebral lesions.

Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature.

Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD.

Engineered porous scaffolds for periprosthetic infection prevention.

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1week, the engineered construct still inhibits the bacterial growth.

Novel bioceramic-reinforced hydrogel for alveolar bone regeneration.

Unlabelled: The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained.

Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task.

Unlabelled: The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells.

Treatment of Fluorosis Spots Using a Resin Infiltration Technique: 14-month Follow-up.

The aim of this study was to report a clinical case of moderate fluorosis spots treated with infiltration of low-viscosity resin. A commercial resin was applied to the facial surfaces on the anterior teeth in both the maxillary and mandibular arches. The white spots of fluorosis lost their whitish appearance and appeared similar to sound enamel.

Patients with breakthrough reactions to iodinated contrast media have low incidence of positive skin tests.

Background: The term "breakthrough reactions" designates repeated hypersensitivity reactions to iodinated contrast media (ICM) despite premedication with glucocorticoids and antihistamines. We aimed to retrospectively evaluate the rate of positive skin test (STs) in our cohort of patients with previous breakthrough reactions to different ICMs.

Methods: A series of 35 patients, who experienced at least one breakthrough reaction to ICM and who underwent STs within 6 months from the reaction were studied, and results were compared to a control group of patients with a first hypersensitivity reaction occurred without premedication.

ASSET: Analysis of Sequences of Synchronous Events in Massively Parallel Spike Trains.

With the ability to observe the activity from large numbers of neurons simultaneously using modern recording technologies, the chance to identify sub-networks involved in coordinated processing increases. Sequences of synchronous spike events (SSEs) constitute one type of such coordinated spiking that propagates activity in a temporally precise manner. The synfire chain was proposed as one potential model for such network processing.

Defining the identity of mouse embryonic dermal fibroblasts.

Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair.