Hodge theory and deformations of affine cones of subcanonical projective varieties:

We investigate the relation between the Hodge theory of a smooth subcanonical n-dimensional projective variety X and the deformation theory of the affine cone A_X over X. We start by identifying H^{n−1,1}_prim(X) as a distinguished graded component of the module of first order deformations of A_X, and later on we show how to identify the whole primitive cohomology of X as a distinguished graded component of the Hochschild cohomology module of the punctured affine cone over X. In the particular case of a projective smooth hypersurface X we recover Griffiths' isomorphism between the primitive cohomology of X and certain distinguished graded components of the Milnor algebra of a polynomial defining X. The main result of the article can be effectively exploited to compute Hodge numbers of smooth subcanonical projective varieties. We provide a few example computation, as well a SINGULAR code, for Fano and Calabi-Yau threefolds

Hospital monitoring, setting and training for home non invasive ventilation.

Although in recent years guidelines have been published in order to define indications, applications and delivery of long-term home non invasive mechanical ventilation (HNMV), there is lack of information with regards to in-hospital assessment, planning and training to initiate and prescribe it. Discontinuation and lack of compliance versus HNMV may affect the follow-up of these patients adding a costly burden for care. The present review proposes an operative flow chart for optimisation of HNMV prescription from initial patient's selection to post discharge follow up including; 1. assessment of the correct choice of ventilator, interfaces, ventilation setting. 2. Timing for different physiological monitoring (arterial gases, mechanics, sleep) 3. Timing for clinical evaluation, machine adaptation, carer training and long term follow-up

Ferroptosis in Friedreich’s ataxia: a metal-induced neurodegenerative disease

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich’s Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress

Public Engagement Provides First Insights on Po Plain Ant Communities and Reveals the Ubiquity of the Cryptic Species Tetramorium immigrans (Hymenoptera, Formicidae)

Ants are considered a useful model for biodiversity monitoring and several of their characteristics make them promising for citizen science (CS) projects. Involving a wide range of public figures into collecting valuable data on the effect of human impact on ant biodiversity, the School of Ants (SoA) project represents one of the very few attempts to explore the potential of these insects in CS. Through the collaboration with the "BioBlitz Lombardia" project, we tested the SoA protocol on 12 Northern Italy parks, ranging from urban green to subalpine protected sites. As a result, we obtained some of the very first quantitative data characterizing the ants of this region, recording 30 species and highlighting some interesting ecological patterns. These data revealed the ubiquitous presence of the recently taxonomically defined cryptic species Tetramorium immigrans, which appears to be probably introduced in the region. We also discuss advantages and criticisms encountered applying the SoA protocol, originally intended for schools, to new categories of volunteers, from BioBlitz participants to park operators, suggesting best practices based on our experience

The Inorganic Side of NGF: Copper(II) And Zinc(II) Affect the NGF Mimicking Signalling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

The nerve growth factor (NGF) N-terminus peptide, NGF(1-14), and its acetylated form, Ac-NGF(1-14), were investigated to scrutinise the ability of this neurotrophin domain to mimic the whole protein. Theoretical calculations demonstrated that non-covalent forces assist the molecular recognition of TrkA receptor for both peptides. Combined parallel tempering/docking simulations discriminated the effect of the N-terminal acetylation on the recognition of NGF(1-14) towards the domain 5 of TrkA (TrkA-D5). Experimental findings demonstrated that both NGF(1-14) and Ac-NGF(1-14) activate TrkA signaling pathways essential for neuronal survival. The NGF-induced TrkA internalization was slightly inhibited in the presence of Cu2+ and Zn2+ ions, whereas the metal ions elicited the NGF(1-14)-induced internalization of TrkA and no significant differences were found in the weak Ac-NGF(1-14)-induced receptor internalization. The crucial role of the metals was confirmed by experiments with the metal-chelator bathocuproine disulfonic acid, which discriminated different levels of inhibitory effects in the signalling cascade, due to different metal affinity of NGF, the free amino and the acetylated peptides. The NGF signaling cascade, activated by NGF (1−14) and Ac-NGF(1-14), induced CREB phosphorylation, but the copper addition further stimulated the Akt, ERK and CREB phosphorylation only for NGF and NGF(1-14). A dynamic and quick influx of both peptides into PC12 cells was tracked by live cell imaging with confocal microscopy. A significant role of copper ions was found in the modulation of peptide sub-cellular localization, especially at the nuclear level. Furthermore, a strong copper ionophoric ability of NGF(1-14) was measured. The Ac-NGF(1-14) peptide, which binds copper ions with a lower stability constant than NGF(1-14), exhibited a lower nuclear localization with respect to the total cellular uptake. These findings were correlated to the metal-induced increase of CREB and BDNF expression upon NGF(1-14) stimulation. In summary, we here validate NGF(1-14) and Ac-NGF(1-14) as first examples of monomer and linear peptides able to activate the NGF-TrkA signaling cascade. Metal ions modulate the activity of both NGF protein and the NGF-mimicking peptides. Such findings demonstrate that NGF(1-14) sequence can reproduce the signal transduction of whole protein, therefore represent a very promising drug candidate for further preclinical studies

Ergatandromorphism in the Ant Myrmica lobulicornis Nylander, 1857 (Formicidae: Myrmicinae)

Ergatandromorphism is the result of an aberrant development in which part of the body of a social insect shows the traits of the worker caste, while the other resembles a male. It is considered a specific case of gynandromorphism. Specimens with these characteristics have rarely been collected in different ant lineages across the world. Here, we provide the first description of ergatandromorphism in the ant Myrmica lobulicornis Nylander, 1857: an ergatandromorphous specimen was recovered during an arthropod sampling campaign across altitudinal and ecological gradients on the Italian Alps (Stelvio National Park), together with 480 workers and 4 queens of the same species, which expressed the normal phenotype

NF-YA splice variants have different roles on muscle differentiation

The heterotrimeric CCAAT-binding factor NF-Y controls the expression of a multitude of genes involved in cell cycle progression. NF-YA is present in two alternatively spliced isoforms, NF-YAs and NF-YAl, differing in 28 aminoacids in the N-terminal Q-rich activation domain. NF-YAs has been identified as a regulator of stemness and proliferation in mouse embryonic cells (mESCs) and human hematopoietic stem cells (hHSCs), whereas the role of NF-YAl is not clear. In the muscle system, NF-YA expression is observed in proliferating cells, but barely detectable in terminally differentiated cells in vitro and adult skeletal muscle in vivo. Here, we show that NF-YA inactivation in mouse myoblasts impairs both proliferation and differentiation. The overexpression of the two NF-YA isoforms differentially affects myoblasts fate: NF-YAs enhance cell proliferation, while NF-YAl boosts differentiation. The molecular mechanisms were investigated by expression profilings, detailing the opposite programs of the two isoforms. Bioinformatic analysis of the regulated promoters failed to detect a significant presence of CCAAT boxes in the regulated genes. NF-YAl activates directly Mef2D, Six genes, and p57kip2 (Cdkn1c), and indirectly the myogenic regulatory factors (MRFs). Specifically, Cdkn1c activation is induced by NF-Y binding to its CCAAT promoter and by reducing the expression of the lncRNA Kcnq1ot1, a negative regulator of Cdkn1c transcription. Overall, our results indicate that NF-YA alternative splicing is an influential muscle cell determinant, through direct regulation of selected cell cycle blocking genes, and, directly and indirectly, of muscle-specific transcription factors

Social Parasite Ants in the Alps: a New Site of the Vulnerable Myrmica myrmicoxena and New Uppermost Altitudinal Limit for M. microrubra

We conducted a survey on the Alpine fauna of one of the largest Natural Park of the Italian Alps (Stelvio National Park) in the framework of a broad ecological monitoring of Alpine biodiversity. A two-years standardized sampling employing pitfall traps along a 1200 m altitudinal gradient led to the discovery of two interesting inquiline social parasite ants of the genus Myrmica: M. myrmicoxena Forel, 1895 and M. microrubra Seifert, 1993. Myrmica myrmicoxena, which is classified as Vulnerable according to the IUCN Red List, was so far known from only three sites across a narrow geographic range between Italy and Switzerland. Our data support the previous hypothesis over its ecology and host association. Myrmica microrubra is considered an incipient species of high evolutionary interest, sometimes regarded as an intraspecific form of M. rubra. While having a wide distribution in Europe, its presence in Italy was hitherto known only from a single site, and our record extends its altitudinal distribution limit in Europe upwards by about 600 m