Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis

A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis

Allelic Variation and Differential Expression of the mSIN3A Histone Deacetylase Complex Gene Arid4b Promote Mammary Tumor Growth and Metastasis

Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT–rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA–mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer

The reductive glycine pathway allows autotrophic growth of Desulfovibrio desulfuricans

Supplementary informationis available for this paper athttps://doi.org/10.1038/s41467-020-18906-7Six CO2 fixation pathways are known to operate in photoautotrophic and chemoautotrophic microorganisms. Here, we describe chemolithoautotrophic growth of the sulphate-reducing bacterium Desulfovibrio desulfuricans (strain G11) with hydrogen and sulphate as energy substrates. Genomic, transcriptomic, proteomic and metabolomic analyses reveal that D. desulfuricans assimilates CO2 via the reductive glycine pathway, a seventh CO2 fixation pathway. In this pathway, CO2 is first reduced to formate, which is reduced and condensed with a second CO2 to generate glycine. Glycine is further reduced in D. desulfuricans by glycine reductase to acetyl-P, and then to acetyl-CoA, which is condensed with another CO2 to form pyruvate. Ammonia is involved in the operation of the pathway, which is reflected in the dependence of the autotrophic growth rate on the ammonia concentration. Our study demonstrates microbial autotrophic growth fully supported by this highly ATP-efficient CO2 fixation pathway.We acknowledge Änne-Michaelis and William Newell for assistance with the LC-MS forthe metabolomics experiments and Daniel Amador-Noguez for access to the LC-MS usedfor13C intracellular metabolomic analysis. We thank Ines Cardoso Pereira and John vander Oost for critically reading the manuscript. This research was funded by the Neth-erlands Organisation for Scientific Research (NWO) through SIAM Gravitation Grant024.002.002 and the Innovation Program Microbiology (WUR), NJC acknowledgesfunding from NWO through a Rubicon Grant (019.163LW.035) and a Veni Grant(VI.Veni.192.156).info:eu-repo/semantics/publishedVersio

Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C