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The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

This scientific report provides an update of the Xylella spp. host plant database, aiming to provide information and scientific support to risk assessors, risk managers and researchers dealing with Xylella spp. Upon a mandate of the European Commission, EFSA created and regularly updates a database of host plant species of Xylella spp. The current mandate covers the period 2021–2026. This report is related to the 10th version of the database published in Zenodo in the EFSA Knowledge Junction community, covering literature published from 1 July 2023 up to 31 December 2023, and recent Europhyt outbreak notifications. Informative data have been extracted from 39 selected publications. Sixteen new host plants, five genera and one family were identified and added to the database. They were naturally infected by X. fastidiosa subsp. fastidiosa or unknown either in Portugal or the United States. No additional data were retrieved for X. taiwanensis, and no additional multilocus sequence types (STs) were identified worldwide. New information on the tolerant/resistant response of plant species to X. fastidiosa infection were added to the database. The Xylella spp. host plant species were listed in different categories based on the number and type of detection methods applied for each finding. The overall number of Xylella spp. host plants determined with at least two different detection methods or positive with one method either by sequencing or pure culture isolation (category A), reaches now 451 plant species, 204 genera and 70 families. Such numbers rise to 712 plant species, 312 genera and 89 families if considered regardless of the detection methods applied (category E). [ABSTRACT FROM AUTHOR]

Spatial-temporal dynamics of spittlebug populations, together with transmission biology, are of major importance to outline the disease epidemiology of Xylella fastidiosa subsp. pauca in Apulian olive groves. The spread rate of X. fastidiosa is mainly influenced by (i) the pathogen colonization of the host plant; (ii) the acquisition of the pathogen by the vector from an infected plant, and its inoculation to healthy plants; (iii) the vector population dynamics and abundance at different spatial scales; and (iv) the dispersal of the vector. In this contribution we summarize the recent advances in research on insect vectors’ traits—points ii, iii, and iv—focusing on those most relevant to X. fastidiosa epidemic in Apulia. Among the vectors’ bioecological traits influencing the X. fastidiosa epidemic in olive trees, we emphasize the following: natural infectivity and transmission efficiency, phenological timing of both nymphal and adult stage, the role of seminatural vegetation as a vector reservoir in the agroecosystem and landscape, and preferential and directional dispersal capabilities. Despite the research on X. fastidiosa vectors carried out in Europe in the last decade, key uncertainties on insect vectors remain, hampering a thorough understanding of pathogen epidemiology and the development of effective and targeted management strategies. Our goal is to provide a structured and contextualized review of knowledge on X. fastidiosa vectors’ key traits in the Apulian epidemic, highlighting information gaps and stimulating novel research pathways on X. fastidiosa pathosystems in Europe. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.06.006 Byline: Vincenzo Cavalieri (a), Maria Di Bernardo (b), Letizia Anello (b), Giovanni Spinelli (a) Keywords: Homeodomain; Aboral ectoderm; cis-Regulatory module; Gene transfer; Otx; Sox; Myb; Sea urchin embryo; Chromatin ImmunoPrecipitation Abstract: Embryonic development is coordinated by networks of evolutionary conserved regulatory genes encoding transcription factors and components of cell signalling pathways. In the sea urchin embryo, a number of genes encoding transcription factors display territorial restricted expression. Among these, the zygotic Hbox12 homeobox gene is transiently transcribed in a limited number of cells of the animal-lateral half of the early Paracentrotus lividus embryo, whose descendants will constitute part of the ectoderm territory. To obtain insights on the regulation of Hbox12 expression, we have explored the cis-regulatory apparatus of the gene. In this paper, we show that the intergenic region of the tandem Hbox12 repeats drives GFP expression in the presumptive aboral ectoderm and that a 234 bp fragment, defined aboral ectoderm (AE) module, accounts for the restricted expression of the transgene. Within this module, a consensus sequence for a Sox factor and the binding of the Otx activator are both required for correct Hbox12 gene expression. Spatial restriction to the aboral ectoderm is achieved by a combination of different repressive sequence elements. Negative sequence elements necessary for repression in the endomesoderm map within the most upstream 60 bp region and nearby the Sox binding site. Strikingly, a Myb-like consensus is necessary for repression in the oral ectoderm, while down-regulation at the gastrula stage depends on a GA-rich region. These results suggest a role for Hbox12 in aboral ectoderm specification and represent our first attempt in the identification of the gene regulatory circuits involved in this process. Author Affiliation: (a) Dipartimento di Biologia Cellulare e dello Sviluppo A. Monroy, Universita di Palermo, Viale delle Scienze Edificio 16, 90128 Palermo, Italy (b) Istituto di Biomedicina e Immunologia Molecolare A. Monroy-CNR, via Ugo La Malfa 153, 90146 Palermo, Italy Article History: Received 25 October 2007; Revised 23 May 2008; Accepted 3 June 2008

In the sea urchin embryo skeletogenesis is the result of a complex series of molecular and cellular events that coordinate the morphogenetic process. Past and recent evidence strongly indicate that skeletal initiation and growth are strictly dependent on signals emanating from the oral ectodermal wall. As previously suggested, Orthopedia (Otp), a homeodomain-containing transcription factor specifically expressed in a small subset of oral ectoderm cells, might be implicated in this signaling pathway. In this study, we utilize three different strategies to address the issue of whether Otp is an upstream regulator of sketelogenesis. We describe the effects of microinjection of Otp morpholino-substituted antisense oligonucleotides and dominant-negative Otp-engrailed mRNA in Paracentrotus lividus embryos. We demonstrate that inhibition of Otp expression completely abolishes skeletal synthesis. By contrast, coinjection of Otp mRNA and the morpholino antisense oligonucleotide specifically rescues the skeletogenic program. In addition, localized ectodermal expression of the Otp-GFP fusion gene construct driven by the hatching enzyme promoter, induces ectopic and abnormal spiculogenesis. We further show that an indirect target of this homeoprotein is the skeletogenic specific gene SM30, whose expression is known to be under the strict control of the oral ectoderm territory. Based on these results, we conclude that Otp triggers the ectoderm-specific signal that promotes skeletogenesis. Keywords: Orthopedia homeobox; Sea urchin embryo; Skeletogenesis; Morpholino oligonucleotides