A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours

Enhancement of cellular senescence in tumours triggers a stable cell growth arrest and activation of an antitumour immune response that can be exploited for cancer therapy. Currently, there are only a limited number of targeted therapies that act by increasing senescence in cancers, but the majority of them are not selective and also target healthy cells. Here we developed a chemogenomic screening to identify compounds that enhance senescence in PTEN-deficient cells without affecting normal cells. By using this approach, we identified casein kinase 2 (CK2) as a pro-senescent target. Mechanistically, we show that Pten loss increases CK2 levels by activating STAT3. CK2 upregulation in Pten null tumours affects the stability of Pml, an essential regulator of senescence. However, CK2 inhibition stabilizes Pml levels enhancing senescence in Pten null tumours. Taken together, our screening strategy has identified a novel STAT3-CK2-PML network that can be targeted for pro-senescence therapy for cancer

Genome of Herbaspirillum seropedicae Strain SmR1, a Specialized Diazotrophic Endophyte of Tropical Grasses

The molecular mechanisms of plant recognition, colonization, and nutrient exchange between diazotrophic endophytes and plants are scarcely known. Herbaspirillum seropedicae is an endophytic bacterium capable of colonizing intercellular spaces of grasses such as rice and sugar cane. The genome of H. seropedicae strain SmR1 was sequenced and annotated by The Paraná State Genome Programme—GENOPAR. The genome is composed of a circular chromosome of 5,513,887 bp and contains a total of 4,804 genes. The genome sequence revealed that H. seropedicae is a highly versatile microorganism with capacity to metabolize a wide range of carbon and nitrogen sources and with possession of four distinct terminal oxidases. The genome contains a multitude of protein secretion systems, including type I, type II, type III, type V, and type VI secretion systems, and type IV pili, suggesting a high potential to interact with host plants. H. seropedicae is able to synthesize indole acetic acid as reflected by the four IAA biosynthetic pathways present. A gene coding for ACC deaminase, which may be involved in modulating the associated plant ethylene-signaling pathway, is also present. Genes for hemagglutinins/hemolysins/adhesins were found and may play a role in plant cell surface adhesion. These features may endow H. seropedicae with the ability to establish an endophytic life-style in a large number of plant species

Exact Distributed Load Centrality Computation: Algorithms, Convergence, and Applications to Distance Vector Routing

Many optimization techniques for networking protocols take advantage of topological information to improve performance. Often, the topological information at the core of these techniques is a centrality metric such as the Betweenness Centrality (BC) index. BC is, in fact, a centrality metric with many well-known successful applications documented in the literature, from resource allocation to routing. To compute BC, however, each node must run a centralized algorithm and needs to have the global topological knowledge; such requirements limit the feasibility of optimization procedures based on BC. To overcome restrictions of this kind, we present a novel distributed algorithm that requires only local information to compute an alternative similar metric, called Load Centrality (LC). We present the new algorithm together with a proof of its convergence and the analysis of its time complexity. The proposed algorithm is general enough to be integrated with any distance vector (DV) routing protocol. In support of this claim, we provide an implementation on top of Babel, a real-world DV protocol. We use this implementation in an emulation framework to show how LC can be exploited to reduce Babel's convergence time upon node failure, without increasing control overhead. As a key step towards the adoption of centrality-based optimization for routing, we study how the algorithm can be incrementally introduced in a network running a DV routing protocol. We show that even when only a small fraction of nodes participate in the protocol, the algorithm accurately ranks nodes according to their centrality

Are artificial intelligence large language models a reliable tool for difficult differential diagnosis? An a posteriori analysis of a peculiar case of necrotizing otitis externa

Key Clinical Message Large language models have made artificial intelligence readily available to the general public and potentially have a role in healthcare; however, their use in difficult differential diagnosis is still limited, as demonstrated by a case of necrotizing otitis externa. Abstract This case report presents a peculiar case of necrotizing otitis externa (NOE) with skull base involvement which proved diagnostically challenging. The initial patient presentation and the imaging performed on the 78‐year‐old patient suggested a neoplastic rhinopharyngeal lesion and only after several unsuccessful biopsies the patient was transferred to our unit. Upon re‐evaluation of the clinical picture, a clinical hypothesis of NOE with skull base erosion was made and confirmed by identifying Pseudomonas aeruginosa in biopsy specimens of skull base bone and external auditory canal skin. Upon diagnosis confirmation, the patient was treated with culture‐oriented long‐term antibiotics with complete resolution of the disease. Given the complex clinical presentation, we chose to submit a posteriori this NOE case to two large language models (LLM) to test their ability to handle difficult differential diagnoses. LLMs are easily approachable artificial intelligence tools that enable human‐like interaction with the user relying upon large information databases for analyzing queries. The LLMs of choice were ChatGPT‐3 and ChatGPT‐4 and they were requested to analyze the case being provided with only objective clinical and imaging data

GESTÃO DE PROJETOS DE TI EM UM GRANDE BANCO BRASILEIRO DOI:10.7444/fsrj.v1i1.7

The world financial segment is that which has most invested in products and services ground on Information Technology (IT). Brazilian banks follow this standard and have resorted to IT in an intense manner so as to foster competitiveness. Within this context, IT project management has become fundamental.In this study, the objective is to identify the impairments IT project management faces at a large Brazilian bank as of the perception of managers from both the IT and business-related areas. To this extent, a case study was undertaken and a semi-structured questionnaire was applied to 10 individuals that occupy leadership positions in the mentioned fields.Results indicate a lack of project management culture giving rise to: issues concerning IT project scope definition; communication setbacks between and within areas; absence of strategic alignment amongst involved areas; difficulty in perceiving an overall picture of projects; mismatch between project prioritization and delivery deadlines.Key-words: Project Management. Information Technology. Banking.O setor financeiro mundial é o que mais tem investido em produtos e serviços apoiado fundamentalmente pela Tecnologia da Informação (TI). Os bancos brasileiros seguem este padrão e têm utilizado a TI de forma intensa, visando aumentar a competitividade. Neste contexto, a gestão de projetos de TI tornou-se fundamental. Neste estudo, objetiva-se identificar as dificuldades da gestão de projetos de TI em um grande banco brasileiro a partir da percepção dos gestores da área de TI e de Negócio. Para tanto, realizou-se um estudo de caso e aplicou-se um questionário semi-estruturado a 10 indivíduos que ocupam cargo de chefia nas áreas mencionadas. Os resultados apontam para a falta de uma cultura de gestão de projetos, que ocasiona: problemas na definição do escopo do projeto de TI; falhas comunicação inter e intra áreas; falta de alinhamento estratégico entre as áreas envolvidas; dificuldade de se ter uma visão global dos projetos; e descasamento entre priorização dos projetos e prazos de entrega.Palavras-chave: Gestão de Projetos. Tecnologia da Informação. Bancos.