Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Understanding and predicting animal movements and distributions in the Anthropocene

\ua9 2025 The Author(s). Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society. Predicting animal movements and spatial distributions is crucial for our comprehension of ecological processes and provides key evidence for conserving and managing populations, species and ecosystems. Notwithstanding considerable progress in movement ecology in recent decades, developing robust predictions for rapidly changing environments remains challenging. To accurately predict the effects of anthropogenic change, it is important to first identify the defining features of human-modified environments and their consequences on the drivers of animal movement. We review and discuss these features within the movement ecology framework, describing relationships between external environment, internal state, navigation and motion capacity. Developing robust predictions under novel situations requires models moving beyond purely correlative approaches to a dynamical systems perspective. This requires increased mechanistic modelling, using functional parameters derived from first principles of animal movement and decision-making. Theory and empirical observations should be better integrated by using experimental approaches. Models should be fitted to new and historic data gathered across a wide range of contrasting environmental conditions. We need therefore a targeted and supervised approach to data collection, increasing the range of studied taxa and carefully considering issues of scale and bias, and mechanistic modelling. Thus, we caution against the indiscriminate non-supervised use of citizen science data, AI and machine learning models. We highlight the challenges and opportunities of incorporating movement predictions into management actions and policy. Rewilding and translocation schemes offer exciting opportunities to collect data from novel environments, enabling tests of model predictions across varied contexts and scales. Adaptive management frameworks in particular, based on a stepwise iterative process, including predictions and refinements, provide exciting opportunities of mutual benefit to movement ecology and conservation. In conclusion, movement ecology is on the verge of transforming from a descriptive to a predictive science. This is a timely progression, given that robust predictions under rapidly changing environmental conditions are now more urgently needed than ever for evidence-based management and policy decisions. Our key aim now is not to describe the existing data as well as possible, but rather to understand the underlying mechanisms and develop models with reliable predictive ability in novel situations

Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway

Impact of jet-production data on the next-to-next-to-leading-order determination of HERAPDF2.0 parton distributions

The HERAPDF2.0 ensemble of parton distribution functions (PDFs) was introduced in 2015. The final stage is presented, a next-to-next-to-leading-order (NNLO) analysis of the HERA data on inclusive deep inelastic ep scattering together with jet data as published by the H1 and ZEUS collaborations. A perturbative QCD fit, simultaneously of αs(M2Z) and the PDFs, was performed with the result αs(M2Z)=0.1156±0.0011 (exp) +0.0001−0.0002 (model +parameterisation) ±0.0029 (scale). The PDF sets of HERAPDF2.0Jets NNLO were determined with separate fits using two fixed values of αs(M2Z), αs(M2Z)=0.1155 and 0.118, since the latter value was already chosen for the published HERAPDF2.0 NNLO analysis based on HERA inclusive DIS data only. The different sets of PDFs are presented, evaluated and compared. The consistency of the PDFs determined with and without the jet data demonstrates the consistency of HERA inclusive and jet-production cross-section data. The inclusion of the jet data reduced the uncertainty on the gluon PDF. Predictions based on the PDFs of HERAPDF2.0Jets NNLO give an excellent description of the jet-production data used as input

Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology

Phosphoinositides play a central role in the control of several cellular events including actin cytoskeleton organization. Here we show that, upon infection of epithelial cells with the Gram-negative pathogen Shigella flexneri, the virulence factor IpgD is translocated directly into eukaryotic cells and acts as a potent inositol 4-phosphatase that specifically dephosphorylates phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] into phosphatidylinositol 5-monophosphate [PtdIns(5)P] that then accumulates. Transfection experiments indicate that the transformation of PtdIns(4,5)P(2) into PtdIns(5)P by IpgD is responsible for dramatic morphological changes of the host cell, leading to a decrease in membrane tether force associated with membrane blebbing and actin filament remodelling. These data provide the molecular basis for a new mechanism employed by a pathogenic bacterium to promote membrane ruffling at the entry site

Here or there? Consumer reactions to corporate social responsibility initiatives: Egocentric tendencies and their moderators

Egocentrism, Consumer behavior, Corporate social responsibility, Identity,

Truncated RUNX1 protein generated by a novel t(1;21)(p32;q22) chromosomal translocation impairs the proliferation and differentiation of human hematopoietic progenitors

This work was supported by an INTRASALUD project PI 12-00425 to JCC. We thank all the coworkers in our laboratory for their excellent technical assistance.We have identified a new t(1;21)(p32;q22) chromosomal translocation in a MDS/AML patient that results in expression of an aberrant C-terminally truncated RUNX1 protein lacking several regulatory domains. As similar truncated RUNX1 proteins are generated by genetic aberrations including chromosomal translocations and point mutations, we used the t(1;21)(p32;q22) chromosomal translocation as a model to explore whether C-terminally truncated RUNX1 proteins trigger effects similar to those induced by well-characterized leukemogenic RUNX1 fusion genes. In vitro analysis of transduced human hematopoietic/progenitor stem cells showed that truncated RUNX1 proteins increase proliferation and self-renewal and disrupt the differentiation program by interfering with RUNX1b. These effects are similar to but milder than those induced by the RUNX1/ETO fusion protein. GSEA analysis confirmed similar altered gene expression patterns in the truncated RUNX1 and RUNX1/ETO models, with both models showing alterations in genes involved in self-renewal and leukemogenesis, including homeobox genes, primitive erythroid genes and leukemogenic transcription factors. We propose that C-terminally truncated RUNX1 proteins can contribute to leukemogenesis in a similar way to RUNX1 fusion genes but through a milder phenotype.S