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In situ architecture, function, and evolution of a contractile injection system

Jue, 08/17/2017 - 11:30

Contractile injection systems mediate bacterial cell-cell interactions by a bacteriophage tail–like structure. In contrast to extracellular systems, the type 6 secretion system (T6SS) is defined by intracellular localization and attachment to the cytoplasmic membrane. Here we used cryo-focused ion beam milling, electron cryotomography, and functional assays to study a T6SS in Amoebophilus asiaticus. The in situ architecture revealed three modules, including a contractile sheath-tube, a baseplate, and an anchor. All modules showed conformational changes upon firing. Lateral baseplate interactions coordinated T6SSs in hexagonal arrays. The system mediated interactions with host membranes and may participate in phagosome escape. Evolutionary sequence analyses predicted that T6SSs are more widespread than previously thought. Our insights form the basis for understanding T6SS key concepts and exploring T6SS diversity.

Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice

Jue, 08/17/2017 - 11:30

The sexual differentiation paradigm contends that the female pattern of the reproductive system is established by default because the male reproductive tracts (Wolffian ducts) in the female degenerate owing to a lack of androgen. Here, we discovered that female mouse embryos lacking Coup-tfII (chicken ovalbumin upstream promoter transcription factor II) in the Wolffian duct mesenchyme became intersex—possessing both female and male reproductive tracts. Retention of Wolffian ducts was not caused by ectopic androgen production or action. Instead, enhanced phosphorylated extracellular signal-regulated kinase signaling in Wolffian duct epithelium was responsible for the retention of male structures in an androgen-independent manner. We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance.

New Products

Jue, 08/17/2017 - 11:30

When personal becomes professional

Jue, 08/17/2017 - 11:30

Collaborative environmental governance: Achieving collective action in social-ecological systems

Jue, 08/17/2017 - 11:30

Managing ecosystems is challenging because of the high number of stakeholders, the permeability of man-made political and jurisdictional demarcations in relation to the temporal and spatial extent of biophysical processes, and a limited understanding of complex ecosystem and societal dynamics. Given these conditions, collaborative governance is commonly put forward as the preferred means of addressing environmental problems. Under this paradigm, a deeper understanding of if, when, and how collaboration is effective, and when other means of addressing environmental problems are better suited, is needed. Interdisciplinary research on collaborative networks demonstrates that which actors get involved, with whom they collaborate, and in what ways they are tied to the structures of the ecosystems have profound implications on actors’ abilities to address different types of environmental problems.

A pathology atlas of the human cancer transcriptome

Jue, 08/17/2017 - 11:30

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

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