Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.

Acetogenic bacteria are obligate anaerobes with the ability of converting carbon dioxide and other one‐carbon substrates into acetate through the Wood–Ljungdahl (WL) pathway. These substrates are becoming increasingly important feedstock in industrial microbiology. The main potential industrial application of acetogenic bacteria is the production of metabolites that constitute renewable energy sources (biofuel); such bacteria are of particular interest for this purpose thanks to their low energy requirements for large‐scale cultivation. Here, we report new genome sequences for four species, three of them are reported for the first time, namely Acetobacterium paludosum DSM 8237, Acetobacterium tundrae DSM 917, Acetobacterium bakii DSM 8239, and Alkalibaculum bacchi DSM 221123. We performed a comparative genomic analysis focused on the WL pathway's genes and their encoded proteins, using Acetobacterium woodii as a reference genome. The Average Nucleotide Identity (ANI) values ranged from 70% to 95% over an alignment length of 5.4–6.5 Mbp. The core genome consisted of 363 genes, whereas the number of unique genes in a single genome ranged from 486 in A. tundrae to 2360 in A.bacchi. No significant rearrangements were detected in the gene order for the Wood–Ljungdahl pathway however, two species showed variations in genes involved in formate metabolism: A. paludosum harbor two copies of fhs1, and A. bakii a truncated fdhF1. The analysis of protein networks highlighted the expansion of protein orthologues in A. woodii compared to A. bacchi, whereas protein networks involved in the WL pathway were more conserved. This study has increased our understanding on the evolution of the WL pathway in acetogenic bacteria.

Erwinia amylovora is the etiological agent of fire blight, a devastating disease which is a global threat to commercial apple and pear production. The Erwinia genus includes a wide range of different species belonging to plant pathogens, epiphytes and even opportunistic human pathogens. The aim of the present study is to understand, within the Erwinia genus, the genetic differences between phytopathogenic strains and those strains not reported to be phytopathogenic. The genes related to the hydroxamate siderophores iron uptake have been considered due to their potential druggability. In E. amylovora siderophore-mediated iron acquisition plays a relevant role in the progression of Fire blight. Here we analyzed the taxonomic relations within Erwinia genus and the relevance of the genes related to the siderophore-mediated iron uptake pathway. The results of this study highlight the presence of a well-defined sub-group of Rosaceae infecting species taxonomically and genetically related with a high number of conserved core genes. The analysis of the complete ferrioxamine transport system has led to the identification of two genes exclusively present in the Rosaceae infecting strains.

The avalanche of genomic data generated from the SARS-CoV-2 virus requires the development of tools to detect and monitor its mutations across the world. Here, we present a webtool, coronapp , dedicated to easily processing user-provided SARS-CoV-2 genomic sequences and visualizing current worldwide status of SARS-CoV-2 mutations. The webtool allows users to highlight mutations and categorize them by frequency, country, genomic location and effect on protein sequences, and to monitor their presence in the population over time. The tool is available at http://giorgilab.unibo.it/coronapp/ for the worldwide dataset and at http://giorgilab.unibo.it/coronannotator/ for the annotation of user-provided sequences. The full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronapp Data Availability Statement: The data that support the findings of this study derive from the GISAID consortium and are openly available in Github, in Rdata format for the R environment, in files results.rda and metadata.rda, at the following link: https://github.com/federicogiorgi/giorgilab/tree/master/coronapp/data

Background: Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms with limited therapeutic options and increasing clinical incidence. Focal adhesion kinase (FAK) has been implicated in oncogenic processes across various tumor types; however, its specific role in GI-NET biology remains inadequately characterized. This study investigates the impact of FAK inhibition on GI-NET cell survival, invasive potential, and gene regulation, with the aim of evaluating FAK as a therapeutic target. Methods: Human GI-NET cell lines (GOT1 and COLO320DM) were treated with Y15, a kinase inhibitor, and PROTAC-FAK (BI-0319), a degrader that abrogates both enzymatic and scaffold functions. siRNA-mediated knockdown of FAK was employed for functional validation. Assays assessing viability and apoptosis were performed in both 2D and 3D culture conditions, while invasion and colony formation were assessed in 2D culture. Western blotting, immunofluorescence, and qRT-PCR were used to evaluate molecular effects. Public transcriptomic datasets were analyzed to assess PTK2 expression across NET subtypes. Results: FAK inhibition reduced cell viability, colony formation, and invasive capacity. PROTAC-FAK, but not Y15, decreased H3K9 acetylation, indicating scaffold-dependent epigenetic modulation. On the other hand, both PROTAC-FAK and Y15 decreased H3K4 methylation levels, further supporting the role of FAK in chromatin regulation. Both compounds suppressed ERK1/2 phosphorylation and modulated RB1 expression, which was further validated by FAK knockdown. In silico analysis revealed elevated PTK2 expression in rectal and small intestinal NETs relative to pancreatic NETs. Conclusion: These findings identify FAK as a regulator of oncogenic and epigenetic pathways in GI-NETs and support its therapeutic targeting, particularly through degradation strategies that inhibit its non-catalytic functions. Highlights: