Suchergebnisse

The mid-17th century is characterized by a cluster of explosive volcanic eruptions in the 1630s and 1640s, climatic conditions culminating in the Maunder Minimum as well as political instability and famine in regions of Western and Northern Europe as well as China and Japan. This contribution investigates the sources of the eruptions of the 1630s and 1640s and their possible impact on contemporary climate using ice-core, tree-ring and historical evidence, but will also look into the socio-political context in which they occurred and the human responses they may have triggered. Three distinct sulfur peaks are found in the Greenland ice core record in 1637, 1641-42 and 1646. In Antarctica, only one unambiguous sulfate spike is recorded, peaking in 1642. The resulting bipolar sulfur peak in 1641-1642 can likely be ascribed to the eruption of Mount Parker (6°N, Philippines) on December 26, 1640, but sulfate emitted from Koma-ga-take (42°N, Japan) volcano on July 31, 1641, has potentially also contributed to the sulphate concentrations observed in Greenland at this time. The smaller peaks in 1637 and 1646 can be potentially attributed to the eruptions of Hekla (63°N, Iceland) and Shiveluch (56°N, Russia), respectively. To date, however, none of the candidate volcanoes for the mid-17th century sulphate peaks have been confirmed with tephra preserved in ice cores. Tree-ring and written sources point to cold conditions in the late 1630s and early 1640s in various parts of Europe, and to poor harvests. Yet the early 17th century was also characterized by widespread warfare across Europe – and in particular the Thirty Years' War (1618–1648) – rendering any attribution of socio-economic crisis to volcanism challenging. In China and Japan, historical sources point to extreme droughts and famines starting in 1638 (China) and 1640 (Japan), thereby preceding the eruptions of Koma-ga-take (July 31, 1640) and Mount Parker (January 4, 1641). The case of the eruption cluster between 1637 and 1646 and the climatic and societal ...

The mid-17 th century is characterized by a cluster of explosive volcanic eruptions in the 1630s and 1640s, deteriorating climatic conditions culminating in the Maunder Minimum as well as political instability and famine in regions of Western and Northern Europe as well as China and Japan. This contribution investigates the sources of the eruptions of the 1630s and 1640s and their possible impact on contemporary climate using ice-core, tree-ring and historical evidence, but will also look into the socio-political context in which they occurred and the human responses they may have triggered. Three distinct sulfur peaks are found in the Greenland ice core record in 1637, 1641–42 and 1646. In Antarctica, only one unambiguous sulfate spike is recorded, peaking in 1642. The resulting bipolar sulfur peak in 1641–1642 can likely be ascribed to the eruption of Mount Parker (6° N, Philippines) on December 26, 1640, but sulfate emitted from Koma-ga-take (42° N, Japan) volcano on July 31, 1641, has potentially also contributed to the sulphate concentrations observed in Greenland at this time. The smaller peaks in 1637 and 1646 can be potentially attributed to the eruptions of Hekla (63° N, Iceland) and Shiveluch (56° N, Russia), respectively. To date, however, none of the candidate volcanoes for the mid-17 th century sulphate peaks have been confirmed with tephra preserved in ice cores. Tree-ring and written sources point to severe and cold conditions in the late 1630s and early 1640s in various parts of Europe, and to poor harvests. Yet the early 17 th century was also characterized by widespread warfare across Europe – and in particular the Thirty Years' War (1618–1648), rendering any attribution of socio-economic crisis to volcanism challenging. In China and Japan, historical sources point to extreme droughts and famines starting in the late 1630s, and thus preceding the eruptions by some years. The case of the eruption cluster in the late 1630s and early 1640s and the climatic and societal conditions recorded in its aftermath thus offer a textbook example of difficulties in (i) unambiguously distinguishing volcanically induced cooling, wetting or drying from natural climate variability, and (ii) attributing political instability, harvest failure and famines solely to volcanic climatic impacts. This example shows that the impacts of past volcanism must always be studied within the contemporary socio-economic contexts, but that it is also time to most past reductive framings and sometimes reactionary oppositional stances in which climate (and environment more broadly) either is or is not deemed an important contributor to major historical events.

Objective:b-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. We previouslyshowed that increased miR-7 levels triggerb-cell dedifferentiation and diabetes. We usedb-cell-specific miR-7 overexpressing mice (Tg7) to testthe hypothesis that loss ofb-cell identity triggered by miR-7 overexpression alters islet gene expression and islet microenvironment in diabetes.Methods:We performed bulk and single-cell RNA sequencing (RNA-seq) in islets obtained fromb-cell-specific miR-7 overexpressing mice(Tg7). We carried out loss- and gain-of-function experiments in MIN6 and EndoC-bH1 cell lines. We analysed previously published mouse andhuman T2D data sets.Results:Bulk RNA-seq revealed thatb-cell dedifferentiation is associated with the induction of genes associated with epithelial-to-mesenchymal transition (EMT) in prediabetic (2-week-old) and diabetic (12-week-old) Tg7 mice. Single-cell RNA-seq (scRNA-seq) indicatedthat this EMT signature is enriched specifically inb-cells. These molecular changes are associated with a weakening ofb-cell:b-cell contacts,increased extracellular matrix (ECM) deposition, and TGFb-dependent isletfibrosis. We found that the mesenchymal reprogramming ofb-cells isexplained in part by the downregulation ofPdx1and its inability to regulate a myriad of epithelial-specific genes expressed inb-cells. Notableamong genes transactivated byPdx1isOvol2, which encodes a transcriptional repressor of the EMT transcription factorZeb2. Followingcompromisedb-cell identity, the reduction inPdx1gene expression causes a decrease inOvol2protein, triggering mesenchymal reprogrammingofb-cells through the induction ofZeb2. We provided evidence that EMT signalling associated with the upregulation ofZeb2expression is amolecular feature of islets in T2D subjects.Conclusions:Our study indicates that miR-7-mediatedb-cell dedifferentiation induces EMT signalling and a chronic response to tissue injury,which alters the islet microenvironment and predisposes tofibrosis. This research suggests that regulators of EMT signalling may represent noveltherapeutic targets for treatingb-cell dysfunction andfibrosis in T2D. ; Published version ; This study was supported by core support from the Medical Research Council UK to the London Institute of Medical Sciences grant MC-A654-5QC20. G.A.R. was supported by a Wellcome Trust Senior Investigator Award (WT098424AIA) and Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, and MR/L020149/1), Experimental Challenge Grant (DIVA MR/L02036X/1), MRC (MR/N00275X/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, and BDA 16/0005485), Imperial Confidence in Concept (ICiC) grants, and a Royal Society Wolfson Research Merit Award. This study was also supported by the European Union's Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115881 (RHAPSODY) to G.A.R. and M.S. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. A.T. was supported by Medical Research Council Grant MR/R010676/1.