Search

Fyn is a tyrosine kinase belonging to the Src family (Src-Family-Kinase, SFK), ubiquitously expressed. Previously, we report that Fyn is important in stress erythropoiesis. Here, we show that in red cells Fyn specifically stimulates G6PD activity, resulting in a 3-fold increase enzyme catalytic activity (kcat) by phosphorylating tyrosine (Tyr)-401. We found Tyr-401 on G6PD as functional target of Fyn in normal human red blood cells (RBC), being undetectable in G6PD deficient RBCs (G6PD-Mediterranean and G6PD-Genova). Indeed, Tyr-401 is located to a region of the G6PD molecule critical for the formation of the enzymatically active dimer. Amino acid replacements in this region are mostly associated with a chronic hemolysis phenotype. Using mutagenesis approach, we demonstrated that the phosphorylation status of Tyr401 modulates the interaction of G6PD with G6P and stabilizes G6PD in a catalytically more efficient conformation. RBCs from Fyn-/−mice are defective in G6PD activity, resulting in increased susceptibility to primaquine-induced intravascular hemolysis. This negatively affected the recycling of reduced Prx2 in response to oxidative stress, indicating that defective G6PD phosphorylation impairs defense against oxidation. In human RBCs, we confirm the involvement of the thioredoxin/Prx2 system in the increase vulnerability of G6PD deficient RBCs to oxidation. In conclusion, our data suggest that Fyn is an oxidative radical sensor, and that Fyn-mediated Tyr-401 phosphorylation, by increasing G6PD activity, plays an important role in the physiology of RBCs. Failure of G6PD activation by this mechanism may be a major limiting factor in the ability of G6PD deficient RBCs to withstand oxidative stress.

Salmonid fish have become ecological and research models of study in the field of conservation genetics and genomics. Over the last decade, brown trout have received a high level of interest in research and publications. The term Salmo trutta complex is used to indicate the large number of geographic forms present in the species Salmo trutta. In Europe, the S. trutta complex consists (based on mitochondrial DNA control region analysis) of seven major evolutionary lineages: Atlantic (AT), Mediterranean (ME), Adriatic (AD), Danubian (DA), Marmoratus (MA), Duero (DU) and Tigris (TI). In several nations, the difficulty of identifying some lineages derives from their wide phenotypic and geographic plasticity and the presence of mixed lineages (due to introgressive hybridization with domestic AT populations). In Italy, the S. trutta complex populations living in the Tyrrhenian area and on the main islands (Sicily, Sardinia and Corsica) showed high genetic diversity. Currently, on the Italian Red List, the protected (near threatened) populations are the AD and ME lineages. Recent studies based on traditional (mitochondrial and nuclear markers) and NGS (next-generation sequencing) analyses have clarified some genetic differences between the populations of the Tyrrhenian region, Sicily, Sardinia and Corsica. Native populations in Sardinia belong to the AD lineage, while those living in Corsica are mainly characterized by the AD, MA and ME haplotypes. In Sicily, in the area of the Iblei mountains, an AT lineage (North African) exists. According to some authors, the term Salmo macrostigma should only be used for populations in North Africa. The use of genotyping methods based on mtDNA and nuclear markers and the latest generation sequencing techniques can improve the study of populations and evolutionary lineages in areas where there are overlaps and hybridization phenomena.

Mutations in neurofibromin, a Ras GTPase-activating protein, lead to the tumor predisposition syndrome neurofibromatosis type 1. Here, we report that cells lacking neurofibromin exhibit enhanced glycolysis and decreased respiration in a Ras/ERK-dependent way. In the mitochondrial matrix of neurofibromin-deficient cells, a fraction of active ERK1/2 associates with succinate dehydrogenase (SDH) and TRAP1, a chaperone that promotes the accumulation of the oncometabolite succinate by inhibiting SDH. ERK1/2 enhances both formation of this multimeric complex and SDH inhibition. ERK1/2 kinase activity is favored by the interaction with TRAP1, and TRAP1 is, in turn, phosphorylated in an ERK1/2-dependent way. TRAP1 silencing or mutagenesis at the serine residues targeted by ERK1/2 abrogates tumorigenicity, a phenotype that is reverted by addition of a cell-permeable succinate analog. Our findings reveal that Ras/ERK signaling controls the metabolic changes orchestrated by TRAP1 that have a key role in tumor growth and are a promising target for anti-neoplastic strategies.

In the present work, we demonstrate how drone surveys coupled with structure-from-motion (SfM) photogrammetry can help to collect huge amounts of very detailed data even in rough terrains where logistics can affect classical field surveys. The area of study is located in the NW part of the Krafla Fissure Swarm (NE Iceland), a volcanotectonic rift composed of eruptive centres, extension fractures, and normal faults. The surveyed sector is characterized by the presence of a hyaloclastite ridge composed of deposits dated, on a stratigraphic basis, to the Weichselian High Glacial (29.1–12.1 ka BP), and a series of lava flows mostly dating back to 11–12 ka BP. The integration of remotely sensed surveys and field inspections enabled us to recognize that this segment of the Krafla rift is made of grabens arranged en-échelon with a left-stepping geometry. A major graben increases in width in correspondence of the hyaloclastite cone; we interpret this geometry as resulting from the mechanical contrast between the stiffer lava succession and the softer hyaloclastites, which favours the development of concentric faults. We also measured a total extension of 16.6 m and 11.2 m along the fractures affecting the lava units, and a total extension in the hyaloclastites of 29.3 m. This produces an extension rate of 1.4 mm/yr in the Holocene lavas and 1.7 ± 0.7 mm/yr in the Weichselian hyaloclastite deposits. The spreading direction we obtained for this area is N97.7° E, resulting from the av. of 568 opening direction values.

Astaxanthin (Asta), a photo-protective red pigment of the carotenoid family, is known for its multiple beneficial properties. In this study, the effects of Asta on isolated human sperm were evaluated. Capacitation involves a series of transformations to let sperm acquire the correct features for potential oocyte fertilization, including the generation of a controlled amount of reactive oxygen species (ROS), cholesterol depletion of the sperm outer membrane, and protein tyrosine phosphorylation (Tyr-P) process in the head region. Volunteers, with normal spermiogram values, were divided in two separate groups on the basis of their ability to generate the correct content of endogenous ROS. Both patient group (PG) and control group (CG) were analysed for Tyr-phosphorylation (Tyr-P) pattern and percentages of acrosome-reacted cells (ARC) and non-viable cells (NVC), in the presence or absence of Asta. In addition, the involvement of ROS on membrane reorganization and the presence of Lyn, a Src family kinase associated with lipid rafts, were investigated. Results show that Lyn is present in the membranes of human sperm, mainly confined in midpiece in resting conditions. Following capacitation, Lyn translocated to the head concomitantly with raft relocation, thus allowing the Tyr-P of head proteins. Asta succeeded to trigger Lyn translocation in PG sperm thus bypassing the impaired ROS-related mechanism for rafts and Lyn translocation. In this study, we showed an interdependence between ROS generation and lipid rafts and Lyn relocation leading the cells to undergo the successive acrosome reaction (AR). Asta, by ameliorating PG sperm functioning, may be utilised to decrease male idiopathic infertility.

Brain plasticity is often restricted to critical periods in early life. Here, we show that a key regulator of this process in the visual cortex, Otx2 homeoprotein, is synthesized and secreted globally from the choroid plexus. Consequently, Otx2 is maintained in selected GABA cells unexpectedly throughout the mature forebrain. Genetic disruption of choroid-expressed Otx2 impacts these distant circuits and in the primary visual cortex reopens binocular plasticity to restore vision in amblyopic mice. The potential to regulate adult cortical plasticity through the choroid plexus underscores the importance of this structure in brain physiology and offers therapeutic approaches to recovery from a broad range of neurodevelopmental disorders.

Astaxanthin (Asta), red pigment of the carotenoid family, is known for its anti-oxidant, anti-cancer, anti-diabetic, and anti-inflammatory properties. In this study, we evaluated the effects of Asta on isolated human sperm in the presence of human papillomavirus (HPV) 16 capsid protein, L1. Sperm, purified by gradient separation, were treated with HPV16-L1 in both a dose and time-dependent manner in the absence or presence of 30 min-Asta pre-incubation. Effects of HPV16-L1 alone after Asta pre-incubation were evaluated by rafts (CTB) and Lyn dislocation, Tyr-phosphorylation (Tyr-P) of the head, percentages of acrosome-reacted cells (ARC) and endogenous reactive oxygen species (ROS) generation. Sperm membranes were also analyzed for the HPV16-L1 content. Results show that HPV16-L1 drastically reduced membrane rearrangement with percentage of sperm showing head CTB and Lyn displacement decreasing from 72% to 15.8%, and from 63.1% to 13.9%, respectively. Accordingly, both Tyr-P of the head and ARC decreased from 68.4% to 10.2%, and from 65.7% to 14.6%, respectively. Asta pre-incubation prevented this drop and restored values of the percentage of ARC up to 40.8%. No alteration was found in either the ROS generation curve or sperm motility. In conclusion, Asta is able to preserve sperm by reducing the amount of HPV16-L1 bound onto membranes.

The ICT scene is dominated by short-range intra-datacenter interconnects and networking, requiring high speed and stable operations at high temperatures. GaAs/AlGaAs vertical-cavity surface-emitting lasers (VCSELs) emitting at 850–980 nm have arisen as the main actors in this framework. Starting from our in-house 3D fully comprehensive VCSEL solver VENUS, in this work we present the possibility of downscaling the dimensionality of the simulation, ending up with a multiphysics 1D solver (D1ANA), which is shown to be capable of reproducing the experimental data very well. D1ANA is then extensively applied to optimize high-temperature operation, by modifying cavity detuning and distributed Bragg’s reflector lengths.

In the present work we highlight the effectiveness of integrating different techniques and tools for better surveying, mapping and collecting data in volcanic areas. We use an Immersive Virtual Reality (IVR) approach for data collection, integrated with Geographic Information System (GIS) analysis in a well-known volcanological site in Santorini (Metaxa mine), a site where volcanic processes influenced the island’s industrial development, especially with regard to pumice mining. Specifically, we have focused on: (i) three-dimensional (3D) high-resolution IVR scenario building, based on Structure from Motion photogrammetry (SfM) modeling; (ii) subsequent geological survey, mapping and data collection using IVR; (iii) data analysis, e.g., calculation of extracted volumes, as well as production of new maps in a GIS environment using input data directly from the IVR survey; and finally, (iv) presentation of new outcomes that highlight the importance of the Metaxa Mine as a key geological and volcanological geosite.