NERVE 2.0: boosting the new enhanced reverse vaccinology environment via artificial intelligence and a user-friendly web interface.

Background: Vaccines development in this millennium started by the milestone work on Neisseria meningitidis B, reporting the invention of Reverse Vaccinology (RV), which allows to identify vaccine candidates (VCs) by screening bacterial pathogens genome or proteome through computational analyses. When NERVE (New Enhanced RV Environment), the first RV software integrating tools to perform the selection of VCs, was released, it prompted further development in the field. However, the problem-solving potential of most, if not all, RV programs is still largely unexploited by experimental vaccinologists that impaired by somehow difficult interfaces, requiring bioinformatic skills.

Advanced morphological control over Cu nanowires through a design of experiments approach.

Copper nanowires (CuNWs), featuring anisotropic highly conductive crystalline facets, represent an ideal nanostructure to fabricate on-demand materials as transparent electrodes and efficient electrocatalysts. The development of reliable and robust CuNWs requires achieving a full control over their synthesis and morphology growth, a challenge that continues to puzzle materials scientists. In this study, we systematically investigated the correlation between the critical synthetic parameters and the structural properties of nanowires using a design of experiments (DOE) approach.

An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.

The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent transcription remains unknown. We investigated modulation of metazoan MED interaction with RNA polymerase II (RNA Pol II) by antagonistic effects of the MED26 subunit and the CDK8 kinase module (CKM). Biochemical analysis of CKM-MED showed that the CKM blocks binding of the RNA Pol II carboxy-terminal domain (CTD), preventing RNA Pol II interaction.

Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and often fatal neurodegenerative disease characterized by the loss of Motor Neurons (MNs) in spinal cord, motor cortex and brainstem. Despite significant efforts in the field, the exact pathogenetic mechanisms underlying both familial and sporadic forms of ALS have not been fully elucidated, and the therapeutic possibilities are still very limited. Here we investigate the molecular mechanisms of neurodegeneration induced by chronic exposure to the environmental cyanotoxin L-BMAA, which causes a form of ALS/Parkinson's disease (PD) in several populations consuming food and/or water containing high amounts of this compound.

Copper and silver nanowires for CO electroreduction.

Copper and silver nanowires have been extensively investigated as the next generation of transparent conductive electrodes (TCEs) due to their ability to form percolating networks. Recently, they have been exploited as electrocatalysts for CO reduction. In this review, we present the most recent advances in this field summarizing different strategies used for the synthesis and functionalization/activation of copper and silver nanowires, as well as, the state of the art of their electrochemical performance with particular emphasis on the effect of the nanowire morphology.

HIPK2 in cancer biology and therapy: Recent findings and future perspectives.

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates and regulates a plethora of transcriptional regulators and chromatin modifiers. The heterogeneity of its interactome allows HIPK2 to modulate several cellular processes and signaling pathways, ultimately regulating cell fate and proliferation. Because of its p53-dependent pro-apoptotic activity and its downregulation in many tumor types, HIPK2 is traditionally considered a bone fide tumor suppressor gene.

"Stripe" transcription factors provide accessibility to co-binding partners in mammalian genomes.

Regulatory elements activate promoters by recruiting transcription factors (TFs) to specific motifs. Notably, TF-DNA interactions often depend on cooperativity with colocalized partners, suggesting an underlying cis-regulatory syntax. To explore TF cooperativity in mammals, we analyze ∼500 mouse and human primary cells by combining an atlas of TF motifs, footprints, ChIP-seq, transcriptomes, and accessibility.

Phenotypic Effects of Homeodomain-Interacting Protein Kinase 2 Deletion in Mice.

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates various transcriptional and chromatin regulators, thus modulating numerous important cellular processes, such as proliferation, apoptosis, DNA damage response, and oxidative stress. The role of HIPK2 in the pathogenesis of cancer and fibrosis is well established, and evidence of its involvement in the homeostasis of multiple organs has been recently emerging. We have previously demonstrated that -null (-KO) mice present cerebellar alterations associated with psychomotor abnormalities and that the double ablation of HIPK2 and its interactor HMGA1 causes perinatal death due to respiratory failure.

Loop extrusion mediates physiological Igh locus contraction for RAG scanning.

RAG endonuclease initiates Igh V(D)J recombination in progenitor B cells by binding a J-recombination signal sequence (RSS) within a recombination centre (RC) and then linearly scanning upstream chromatin, presented by loop extrusion mediated by cohesin, for convergent D-RSSs. The utilization of convergently oriented RSSs and cryptic RSSs is intrinsic to long-range RAG scanning. Scanning of RAG from the DJ-RC-RSS to upstream convergent V-RSSs is impeded by D-proximal CTCF-binding elements (CBEs).

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice.

The serine-threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted.

A dynamic link between H/ACA snoRNP components and cytoplasmic stress granules.

Many cell stressors block protein translation, inducing formation of cytoplasmic aggregates. These aggregates, named stress granules (SGs), are composed by translationally stalled ribonucleoproteins and their assembly strongly contributes to cell survival. Composition and dynamics of SGs are thus important starting points for identifying critical factors of the stress response.

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs.

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes.

Update on the Regulation of HIPK1, HIPK2 and HIPK3 Protein Kinases by microRNAs.

Unlabelled: The Homeodomain-Interacting Protein Kinases (HIPKs) HIPK1, HIPK2 and HIPK3 are Ser/Thr kinases which interact with homeobox proteins and other transcription factors, acting as transcriptional coactivators or corepressors. HIPKs contribute to regulate several biological processes, such as signal transduction, apoptosis, embryonic development, DNA-damage response, and cellular proliferation, in response to various extracellular stimuli. Recently it has emerged that, in addition to their role in cancer, fibrosis and diabetes, HIPKs may also be involved in other human diseases, including Amyotrophic Lateral Sclerosis (ALS), Rett syndrome, cerebellar diseases, and retinal vascular dysfunction.

High mobility group A1 protein modulates autophagy in cancer cells.

High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions.

Convergent Effects of Resveratrol and PYK2 on Prostate Cells.

Resveratrol, a dietary polyphenol, is under consideration as chemopreventive and chemotherapeutic agent for several diseases, including cancer. However, its mechanisms of action and its effects on non-tumor cells, fundamental to understand its real efficacy as chemopreventive agent, remain largely unknown. Proline-rich tyrosine kinase 2 (PYK2), a non-receptor tyrosine kinase acting as signaling mediator of different stimuli, behaves as tumor-suppressor in prostate.

Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo.

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis.

Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities.

The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas.

Regulation of HIPK Proteins by MicroRNAs.

Introduction: The homeodomain-interacting protein kinase (HIPK) family consists of four evolutionarily conserved and highly related nuclear serine/threonine kinases of recent discovery. They interact with homeobox proteins and other transcription factors, as well as transcriptional coactivators or corepressors depending on the cellular context. HIPK proteins are sensors for various extracellular stimuli, which control key cellular functions such as signal transduction to downstream effectors that regulate apoptosis, embryonic development, DNA-damage response, and cellular proliferation.

Deregulation of HMGA1 expression induces chromosome instability through regulation of spindle assembly checkpoint genes.

The mitotic spindle assembly checkpoint (SAC) is an essential control system of the cell cycle that contributes to mantain the genomic stability of eukaryotic cells. SAC genes expression is often deregulated in cancer cells, leading to checkpoint impairment and chromosome instability. The mechanisms responsible for the transcriptional regulation and deregulation of these genes are still largely unknown.

Streptococcus anginosus group disseminated infection: case report and review of literature.

Streptococcus anginosus group is widely known for its ability to cause invasive pyogenic infections. There are very few reports of disseminated infections sustained by members of this streptococcal group. We report a case of a highly disseminated infection and analyse previous literature reports.