The importance of major mergers in the build up of stellar mass in brightest cluster galaxies at z=1

Recent independent results from numerical simulations and observations have shown that brightest cluster galaxies (BCGs) have increased their stellar mass by a factor of almost two between z~0.9 and z~0.2. The numerical simulations further suggest that more than half this mass is accreted through major mergers. Using a sample of 18 distant galaxy clusters with over 600 spectroscopically confirmed cluster members between them, we search for observational evidence that major mergers do play a significant role. We find a major merger rate of 0.38 +/- 0.14 mergers per Gyr at z~1. While the uncertainties, which stem from the small size of our sample, are relatively large, our rate is consistent with the results that are derived from numerical simulations. If we assume that this rate continues to the present day and that half of the mass of the companion is accreted onto the BCG during these mergers, then we find that this rate can explain the growth in the stellar mass of the BCGs that is observed and predicted by simulations. Major mergers therefore appear to be playing an important role, perhaps even the dominant one, in the build up of stellar mass in these extraordinary galaxies.Comment: 15 pages, 6 figures, accepted for publication in MNRAS. Reduced data will be made available through the ESO archiv

Gemini Observations of Galaxies in Rich Early Environments (GOGREEN) I : survey description.

We describe a new Large Program in progress on the Gemini North and South telescopes: Gemini Observations of Galaxies in Rich Early Environments (GOGREEN). This is an imaging and deep spectroscopic survey of 21 galaxy systems at 1 10 in halo mass. The scientific objectives include measuring the role of environment in the evolution of low-mass galaxies, and measuring the dynamics and stellar contents of their host haloes. The targets are selected from the SpARCS, SPT, COSMOS, and SXDS surveys, to be the evolutionary counterparts of today's clusters and groups. The new red-sensitive Hamamatsu detectors on GMOS, coupled with the nod-and-shuffle sky subtraction, allow simultaneous wavelength coverage over λ ∼ 0.6–1.05 μm, and this enables a homogeneous and statistically complete redshift survey of galaxies of all types. The spectroscopic sample targets galaxies with AB magnitudes z΄ < 24.25 and [3.6] μm < 22.5, and is therefore statistically complete for stellar masses M* ≳ 1010.3 M⊙, for all galaxy types and over the entire redshift range. Deep, multiwavelength imaging has been acquired over larger fields for most systems, spanning u through K, in addition to deep IRAC imaging at 3.6 μm. The spectroscopy is ∼50 per cent complete as of semester 17A, and we anticipate a final sample of ∼500 new cluster members. Combined with existing spectroscopy on the brighter galaxies from GCLASS, SPT, and other sources, GOGREEN will be a large legacy cluster and field galaxy sample at this redshift that spectroscopically covers a wide range in stellar mass, halo mass, and clustercentric radius

Multiple shades of grey: Opening the black box of public sector executives' hybrid role identities

Public sector reforms of recent decades in Europe have promoted managerialism and aimed at introducing private sector thinking and practices. However, with regard to public sector executives' self-understanding, managerial role identities have not replaced bureaucratic ones; rather, components from both paradigms have combined. In this article, we introduce a bi-dimensional approach (attitudes and practices) that allows for different combinations and forms of hybridity. Empirically, we explore the role identities of public sector executives across Europe, building on survey data from over 7,000 top public officials in 19 countries (COCOPS survey). We identify country-level profiles, as well as patterns across countries, and find that administrative traditions can account for these profiles and patterns only to a limited extent. Rather, they have to be complemented by factors such as stability of the institutional environment (indicating lower shares of hybrid combinations) or extent of reform pressures (indicating higher shares of hybrid combinations)

Galaxy pre-processing in substructures around z∼\sim0.4 galaxy clusters

We present a detailed analysis of galaxy colours in two galaxy clusters at \mbox{z $\sim$ 0.4}, \mbox{MACS J0416.1-2403} and \mbox{MACS J1206.2-0847}, drawn from the CLASH-VLT survey, to investigate the role of pre-processing in the quenching of star formation. We estimate the fractions of red and blue galaxies within the main cluster and the detected substructures and study the trends of the colour fractions as a function of the projected distance from the cluster and substructure centres. Our results show that the colours of cluster and substructure members have consistent spatial distributions. In particular, the colour fractions of galaxies inside substructures follow the same spatial trends observed in the main clusters. Additionally, we find that at large cluster-centric distances \mbox{($r \geq r_{200}$)} the fraction of blue galaxies in both the main clusters and in the substructures is always lower than the average fraction of UVJ-selected star-forming galaxies in the field as measured in the COSMOS/UltraVista data set. We finally estimate environmental quenching efficiencies in the clusters and in the substructures and find that at large distances from the cluster centres, the quenching efficiency of substructures becomes comparable to the quenching efficiency of clusters. Our results suggest that pre-processing plays a significant role in the formation and evolution of passive galaxies in clusters at low redshifts.Comment: Accepted for publication in MNRAS. 28 pages, 14 figures, 20 table

RGBM: regularized gradient boosting machines for identification of the transcriptional regulators of discrete glioma subtypes

We propose a generic framework for gene regulatory network (GRN) inference approached as a feature selection problem. GRNs obtained using Machine Learning techniques are often dense, whereas real GRNs are rather sparse. We use a Tikonov regularization inspired optimal L-curve criterion that utilizes the edge weight distribution for a given target gene to determine the optimal set of TFs associated with it. Our proposed framework allows to incorporate a mechanistic active biding network based on cis-regulatory motif analysis. We evaluate our regularization framework in conjunction with two non-linear ML techniques, namely gradient boosting machines (GBM) and random-forests (GENIE), resulting in a regularized feature selection based method specifically called RGBM and RGENIE respectively. RGBM has been used to identify the main transcription factors that are causally involved as master regulators of the gene expression signature activated in the FGFR3-TACC3-positive glioblastoma. Here, we illustrate that RGBM identifies the main regulators of the molecular subtypes of brain tumors. Our analysis reveals the identity and corresponding biological activities of the master regulators characterizing the difference between G-CIMP-high and G-CIMP-low subtypes and between PA-like and LGm6-GBM, thus providing a clue to the yet undetermined nature of the transcriptional events among these subtypes

Altered centriolar cohesion by CEP250 and appendages impact outcome of patients with pancreatic cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cause of cancer death worldwide. PDACs are characterized by centrosome aberrations, but whether centrosome-related genes influence patient outcomes has not been tested. Methods: Publicly available RNA-sequencing data of patients diagnosed with PDAC were interrogated with unsupervised approaches to identify centrosome protein-encoding genes with prognostic rele&#x2;vance. Candidate genes were validated by immunohistochemistry and multiplex immunofluorescence in a set of clinical PDAC and normal pancreatic tissues. Results: Results showed that two genes CEP250 and CEP170, involved in centrosome linker and centriolar subdistal appendages, were expressed at high levels in PDAC tissues and were correlated with prognosis of PDAC patients in independent databases. Large clustered g-tubulin-labelled centrosomes were linked together by aberrant circular and planar&#x2;shaped CEP250 arrangements in CEP250-high expressing PDACs. Furthermore, PDACs displayed prom&#x2;inent centrosome separation and reduced CEP164-centrosomal labelling associated with acetylated&#x2;tubulin staining compared to normal pancreatic tissues. Interestingly, in a small validation cohort, CEP250-high expressing patients had shorter disease free- and overall-survival and almost none of those who received gemcitabine plus nab-paclitaxel first-line therapy achieved a clinical response. In contrast, weak CEP250 expression was associated with long-term survivors or responses to medical treatments. Conclusions: Alteration of the centriolar cohesion and appendages has effect on the survival of patients with PDAC

Robot-Assisted Extravesical Ureteral Reimplantation (REVUR) in Pediatric Patients: A New Standard of Treatment for Patients with VUR—A Narrative Review

Robot-assisted extravesical ureteral reimplantation (REVUR) was described for the first time in 2004. Since then, the surgical approach of vesicoureteral reflux (VUR) has changed dramatically. The benefits of this technique are great when compared to the laparoscopic or traditional open approaches. A literature search of PubMed was performed to identify articles covering any aspect of REVUR in the pediatric population. A total of 108 papers published over the period 2004-2024 were collected. Of these, 40 studies were considered valuable in terms of obtaining a complete overview of the REVUR technique. This review aimed to describe the current state of the art of REVUR and define it as the new standard technique for surgical management of selected patients with VUR

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer

Background: Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. Methods: We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. Results: We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Conclusions: Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC

Loss of Primary Cilia Potentiates BRAF/MAPK Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil (CROCC) Alterations

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target