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31.
Arctic sea ice extent is now more than two million square kilometres less than it was in the late twentieth century, with important consequences for the climate, the ocean and traditional lifestyles in the Arctic. Although observations show a more or less continuous decline for the past four or five decades, there are few long-term records with which to assess natural sea ice variability. Until now, the question of whether or not current trends are potentially anomalous has therefore remained unanswerable. Here we use a network of high-resolution terrestrial proxies from the circum-Arctic region to reconstruct past extents of summer sea ice, and show that-although extensive uncertainties remain, especially before the sixteenth century-both the duration and magnitude of the current decline in sea ice seem to be unprecedented for the past 1,450 years. Enhanced advection of warm Atlantic water to the Arctic seems to be the main factor driving the decline of sea ice extent on multidecadal timescales, and may result from nonlinear feedbacks between sea ice and the Atlantic meridional overturning circulation. These results reinforce the assertion that sea ice is an active component of Arctic climate variability and that the recent decrease in summer Arctic sea ice is consistent with anthropogenically forced warming. 相似文献
32.
Lorch JM Meteyer CU Behr MJ Boyles JG Cryan PM Hicks AC Ballmann AE Coleman JT Redell DN Reeder DM Blehert DS 《Nature》2011,480(7377):376-378
White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America. The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals. Demonstration of causality is an instrumental step in elucidating the pathogenesis and epidemiology of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease. 相似文献
33.
A. Beqqali W. van Eldik C. Mummery R. Passier 《Cellular and molecular life sciences : CMLS》2009,66(5):800-813
Studies on identification, derivation and characterization of human stem cells in the last decade have led to high expectations
in the field of regenerative medicine. Although it is clear that for successful stem cell-based therapy several obstacles
have to be overcome, other opportunities lay ahead for the use of human stem cells. A more immediate application would be
the development of human models for cell-type specific differentiation and disease in vitro. Cardiomyocytes can be generated from stem cells, which have been shown to follow similar molecular events of cardiac development
in vivo. Furthermore, several monogenic cardiovascular diseases have been described, for which in vitro models in stem cells could be generated. Here, we will discuss the potential of human embryonic stem cells, cardiac stem
cells and the recently described induced pluripotent stem cells as models for cardiac differentiation and disease.
Received 07 August 2008; received after revision 26 September 2008; accepted 03 October 2008 相似文献
34.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
35.
Jana Fischer Gunnar Kleinau Claudia Rutz Denise Zwanziger Noushafarin Khajavi Anne Müller Maren Rehders Klaudia Brix Catherine L. Worth Dagmar Führer Heiko Krude Burkhard Wiesner Ralf Schülein Heike Biebermann 《Cellular and molecular life sciences : CMLS》2018,75(12):2227-2239
G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of Gq/11 by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields. 相似文献
36.
Celso O. Azevedo Simon van Noort David G. Notton 《Journal of Natural History》2018,52(23-24):1537-1549
Holepyris semiruber Kieffer is redescribed and illustrated based on freshly collected specimens. Holepyris semiruber var. striatipleura Kieffer is considered a colour variant of this species and therefore a junior synonym of H. semiruber syn. nov. This species is transferred to Disepyris, D. semiruber (Kieffer) comb. nov., based on the possession of a short 2r-rs&Rs vein in the fore wing and presence of long flat spine-shaped setae on the outer (posterior) surface of the protarsi. The male is described for the first time from new specimens collected in South Africa. This species is recorded for the first time from Namibia and Zimbabwe. All photographs are available on www.waspweb.org. 相似文献
37.
38.
Human skin is permanently exposed to microorganisms, but rarely infected. One reason for this natural resistance might be
the existence of a ‘chemical barrier’ consisting in constitutively and inducibly produced antimicrobial peptides and proteins
(AMPs). Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Apart from being expressed in vivo in inflammatory lesions, some AMPs are also focally expressed in skin in the absence of inflammation. This suggests that
non-inflammatory stimuli of endogenous and/or exogenous origin can also stimulate AMP synthesis without inflammation. Such
mediators might be ideal ‘immune stimulants’ to induce only the innate antimicrobial skin effector molecules without causing
inflammation.
Received 9 August 2005; received after revision 21 October 2005; accepted 16 November 2005 相似文献
39.
40.
Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic
acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place
by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a
general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease,
belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended
our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will
centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human
disease and the way it is produced from phytol.
Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006 相似文献