The true story of Yeti, the "abominable" heterochromatic gene of drosophila melanogaster

The Drosophila Yeti gene (CG40218) was originally identified by recessive lethal mutation and subsequently mapped to the deep pericentromeric heterochromatin of chromosome 2. Functional studies have shown that Yeti encodes a 241 amino acid protein called YETI belonging to the evolutionarily conserved family of Bucentaur (BCNT) proteins and exhibiting a widespread distribution in animals and plants. Later studies have demonstrated that YETI protein: (i) is able to bind both subunits of the microtubule-based motor kinesin-I; (ii) is required for proper chromosome organization in both mitosis and meiosis divisions; and more recently (iii) is a new subunit of dTip60 chromatin remodeling complex. To date, other functions of YETI counterparts in chicken (CENtromere Protein 29, CENP-29), mouse (Cranio Protein 27, CP27), zebrafish and human (CranioFacial Development Protein 1, CFDP1) have been reported in literature, but the fully understanding of the multifaceted molecular function of this protein family remains still unclear. In this review we comprehensively highlight recent work and provide a more extensive hypothesis suggesting a broader range of YETI protein functions in different cellular processes

Knockdown of DOM/Tip60 complex subunits impairs male meiosis of Drosophila melanogaster

ATP-dependent chromatin remodeling complexes are involved in nucleosome sliding and eviction and/or the incorporation of histone variants into chromatin to facilitate several cellular and biological processes, including DNA transcription, replication and repair. The DOM/TIP60 chromatin remodeling complex of Drosophila melanogaster contains 18 subunits, including the DOMINO (DOM), an ATPase that catalyzes the exchange of the canonical H2A with its variant (H2A.V), and TIP60, a lysine-acetyltransferase that acetylates H4, H2A and H2A.V histones. In recent decades, experimental evidence has shown that ATP-dependent chromatin remodeling factors, in addition to their role in chromatin organization, have a functional relevance in cell division. In particular, emerging studies suggested the direct roles of ATP-dependent chromatin remodeling complex subunits in controlling mitosis and cytokinesis in both humans and D. melanogaster. However, little is known about their possible involvement during meiosis. The results of this work show that the knockdown of 12 of DOM/TIP60 complex subunits generates cell division defects that, in turn, cause total/partial sterility in Drosophila males, providing new insights into the functions of chromatin remodelers in cell division control during gametogenesis

Targeted protein degradation tools: overview and future perspectives

Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein

Atti del MoodleMoot Italia 2017

Atti del MoodleMoot Italia 2017 - Dipartimento di Chimica e Tecnologie del Farmaco - Facolt\ue0 di Farmacia e Medicina - Sapienza Universit\ue0 di Roma - 28-30 settembre 2017.Intranet di ateneo ed e-learning \u2013 mondi integratiSi descrive un\u2019esperienza di integrazione del generico sistema LMS \u201cMoodle\u201d all\u2019interno del panorama gi\ue0 consolidato e complesso dei sistemi informativi dell\u2019Ateneo di Verona con l\u2019obiettivo di \u201ccondizionare\u201d lo strumento standard Moodle ad utilizzare logiche universitarie. L\u2019obiettivo viene raggiunto lasciando sostanzialmente inalterata la piattaforma Moodle ed utilizzando le possibilit\ue0 che lo strumento nativamente gi\ue0 offre nel campo dell\u2019integrazione. Il risultato ottenuto va nell\u2019ottica dell\u2019armonizzazione dei sistemi e del miglioramento dell\u2019esperienza utente. Dal punto di vista pratico il risultato del progetto \ue8 una \u201cIntranet\u201d a disposizione di studenti, docenti e personale, che costituisce un punto di accesso unico e semplificato a tutti i servizi on-line dedicati. La realizzazione del sistema si basa sull\u2019implementazione di uno strato di integrazione basato su Liferay che media ed orchestra l\u2019interazione tra sistemi

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1 , JAK3 , STAT3 , and SOCS1 . We also identified mutations in KRAS , TP53 , and TERT . Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes

Evaluation of porous asphalt hydrological performances through rainfall-runoff modelling by EPA SWMM

Over the last few decades, the increase in extreme weather events has caused urban floods to become more and more frequent, with increased risks for road users. Among the different types of pavement structures, permeable pavements (PPs) can effectively increase the hydraulic resilience of the cities since they are specifically designed for reducing runoff by allowing water to infiltrate and be discharged into the soil and/or by drains. This study aims at evaluating the hydrological performance of a Porous Asphalt (PA) using numerical simulations for a case study carried out using EPA SWMM (Storm Water Management Model) software. Several simulations have been carried out, considering different rainfall events, covered areas, and spatial layouts of the permeable pavement itself. The results provide useful information on the use of PA