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An acute immune response underlies the benefit of cardiac stem cell therapy 期刊论文
NATURE, 2020, 577 (7790) : 405-+
作者:  Schmacke, Niklas A.;  Hornung, Veit
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day(1,2), despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biological effect(3). The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischaemic injury(4,5). Here we examine the mechanistic basis for cell therapy in mice after ischaemia-reperfusion injury, and find that-although heart function is enhanced-it is not associated with the production of new cardiomyocytes. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2(+) and CX3CR1(+) macrophages. Intracardiac injection of two distinct types of adult stem cells, cells killed by freezing and thawing or a chemical inducer of the innate immune response all induced a similar regional accumulation of CCR2(+) and CX3CR1(+) macrophages, and provided functional rejuvenation to the heart after ischaemia-reperfusion injury. This selective macrophage response altered the activity of cardiac fibroblasts, reduced the extracellular matrix content in the border zone and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound-healing response that rejuvenates the infarcted area of the heart.


  
Zucchini consensus motifs determine the mechanism of pre-piRNA production 期刊论文
NATURE, 2020, 578 (7794) : 311-+
作者:  Clark, Timothy D.;  Raby, Graham D.;  Roche, Dominique G.;  Binning, Sandra A.;  Speers-Roesch, Ben;  Jutfelt, Fredrik;  Sundin, Josefin
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

PIWI-interacting RNAs (piRNAs) of between approximately 24 and 31 nucleotides in length guide PIWI proteins to silence transposons in animal gonads, thereby ensuring fertility(1). In the biogenesis of piRNAs, PIWI proteins are first loaded with 5 '  -monophosphorylated RNA fragments called pre-pre-piRNAs, which then undergo endonucleolytic cleavage to produce pre-piRNAs(1,2). Subsequently, the 3 '  -ends of pre-piRNAs are trimmed by the exonuclease Trimmer (PNLDC1 in mouse)(3-6) and 2 '  -O-methylated by the methyltransferase Hen1 (HENMT1 in mouse)(7-9), generating mature piRNAs. It is assumed that the endonuclease Zucchini (MitoPLD in mouse) is a major enzyme catalysing the cleavage of pre-pre-piRNAs into pre-piRNAs(10-13). However, direct evidence for this model is lacking, and how pre-piRNAs are generated remains unclear. Here, to analyse pre-piRNA production, we established a Trimmer-knockout silkworm cell line and derived a cell-free system that faithfully recapitulates Zucchini-mediated cleavage of PIWI-loaded pre-pre-piRNAs. We found that pre-piRNAs are generated by parallel Zucchini-dependent and -independent mechanisms. Cleavage by Zucchini occurs at previously unrecognized consensus motifs on pre-pre-piRNAs, requires the RNA helicase Armitage, and is accompanied by 2 '  -O-methylation of pre-piRNAs. By contrast, slicing of pre-pre-piRNAs with weak Zucchini motifs is achieved by downstream complementary piRNAs, producing pre-piRNAs without 2 '  -O-methylation. Regardless of the endonucleolytic mechanism, pre-piRNAs are matured by Trimmer and Hen1. Our findings highlight multiplexed processing of piRNA precursors that supports robust and flexible piRNA biogenesis.


A silkworm model recapitulates key steps of Zucchini-mediated cleavage of pre-pre-piRNA and provides insights into Zucchini-mediated and -independent pathways that generate pre-piRNAs, which converge to a common piRNA maturation step.


  
Feed conversion efficiency in aquaculture: do we measure it correctly? 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2018, 13 (2)
作者:  Fry, Jillian P.;  Mailloux, Nicholas A.;  Love, David C.;  Milli, Michael C.;  Cao, Ling
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
aquaculture  agriculture  food security  animal production efficiency  
Land use for animal production in global change studies: Defining and characterizing a framework 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (11)
作者:  Phelps, Leanne N.;  Kaplan, Jed O.
收藏  |  浏览/下载:22/0  |  提交时间:2019/04/09
animal production  browsing  global change studies  grazing  land cover  land use  livestock  modeling  pasture  rangeland