It is well established that multinucleation is central for osteoclastic bone resorption. However, our knowledge on the mechanisms regulating how many nuclei an osteoclast will have is limited. The ...objective of this study was to investigate donor-related variations in the fusion potential of in vitro-generated osteoclasts. Therefore, CD14
monocytes were isolated from 49 healthy female donors. Donor demographics were compared to the in vivo bone biomarker levels and their monocytes' ability to differentiate into osteoclasts, showing that: (1) C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels increase with age, (2) the number of nuclei per osteoclast in vitro increases with age, and (3) there is a positive correlation between the number of nuclei per osteoclast in vitro and CTX levels in vivo. Furthermore, the expression levels of the gene encoding dendritic cell-specific transmembrane protein (
) of osteoclasts in vitro correlated positively with the number of nuclei per osteoclast, CTX levels in vivo, and donor age. Our results furthermore suggest that these changes in gene expression may be mediated through age-related changes in DNA methylation levels. We conclude that both intrinsic factors and age-induced increase in fusion potential of osteoclasts could be contributing factors for the enhanced bone resorption in vivo, possibly caused by increased expression levels of
.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The last glacial period exhibited abrupt Dansgaard-Oeschger climatic oscillations, evidence of which is preserved in a variety of Northern Hemisphere palaeoclimate archives. Ice cores show that ...Antarctica cooled during the warm phases of the Greenland Dansgaard-Oeschger cycle and vice versa, suggesting an interhemispheric redistribution of heat through a mechanism called the bipolar seesaw. Variations in the Atlantic meridional overturning circulation (AMOC) strength are thought to have been important, but much uncertainty remains regarding the dynamics and trigger of these abrupt events. Key information is contained in the relative phasing of hemispheric climate variations, yet the large, poorly constrained difference between gas age and ice age and the relatively low resolution of methane records from Antarctic ice cores have so far precluded methane-based synchronization at the required sub-centennial precision. Here we use a recently drilled high-accumulation Antarctic ice core to show that, on average, abrupt Greenland warming leads the corresponding Antarctic cooling onset by 218 ± 92 years (2σ) for Dansgaard-Oeschger events, including the Bølling event; Greenland cooling leads the corresponding onset of Antarctic warming by 208 ± 96 years. Our results demonstrate a north-to-south directionality of the abrupt climatic signal, which is propagated to the Southern Hemisphere high latitudes by oceanic rather than atmospheric processes. The similar interpolar phasing of warming and cooling transitions suggests that the transfer time of the climatic signal is independent of the AMOC background state. Our findings confirm a central role for ocean circulation in the bipolar seesaw and provide clear criteria for assessing hypotheses and model simulations of Dansgaard-Oeschger dynamics.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Reconstruction of the long‐term surface temperature history in Antarctica is important for a better understanding of human‐induced climate changes, especially since the Industrial Revolution. We ...present here a surface temperature history spanning the last century at Styx Glacier, located on the eastern coast of northern Victoria Land, which is reconstructed using borehole logging data. Our results indicate that surface temperatures in the 20th century were 1.7 ± 0.4 °C higher than the long term averages over 1600–1900 Common Era, indicating regional warming over the eastern coast of northern Victoria Land. However, we found no evidence for significant warming across the northern Victoria Land since the mid‐20th century. A global reanalysis as well as the reconstruction of proxy records demonstrate that the climate in this region was more affected by changes in the Southern Hemisphere Annular Mode than in the Amundsen‐Bellingshausen Sea Low.
Plain Language Summary
The western coast of the Ross Sea, northern Victoria Land, is one of several regions around the world where the temperature history is highly uncertain. Here we provide a temperature reconstruction using borehole logging data from Styx Glacier. The reconstructed temperature history indicates that the surface temperature at Styx Glacier in the 20th century is higher than in previous centuries, although there is no significant trend since ~1950s. The lack of recent warming trend off the western Ross Sea is in contrast to the warming in the Antarctic Peninsula and West Antarctica.
Key Points
The surface temperature in the 20th century at Styx Glacier (western coast of the Ross Sea) is higher by 1.7 +/− 0.4 degrees than before 1900 CE
No clear warming trend since the mid‐20th century was found in northern Victoria Land, Antarctica
The climate over the western coast of the Ross Sea might be affected by the Southern Hemisphere Annular Mode
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Antarctica, the coldest and driest continent, is home to the largest ice sheet, whose mass is predominantly recharged by snowfall. A common feature of polar regions is the warming associated with ...snowfall, as moist oceanic air and cloud cover increase the surface temperature. Consequently, snow that accumulates on the ice sheet is deposited under unusually warm conditions. Here we use a polar-oriented regional atmospheric model to study the statistical difference between average and snowfall-weighted temperatures. During snowfall, the warm anomaly scales with snowfall amount, with the strongest sensitivity occurring at low-accumulation sites. Heavier snowfall in winter helps to decrease the annual snowfall-weighted temperature, but this effect is overwritten by the event-scale warming associated with precipitating atmospheric systems, which particularly contrast with the extremely cold conditions that occur in winter. Consequently, the seasonal range of snowfall-weighted temperature is reduced by 20 %. On the other hand, the annual snowfall-weighted temperature shows 80 % more interannual variability than the annual temperature due to the irregularity of snowfall occurrence and its associated temperature anomaly. Disturbances of the apparent annual temperature cycle and interannual variability have important consequences for the interpretation of water isotopes in precipitation, which are deposited with snowfall and commonly used for paleotemperature reconstructions from ice cores.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We studied different methods of preparing α-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. ...Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500-700 nm). Increasing ATA concentration (1-7 mg mL) induced a decrease in the association rate (97-93%) and in the adsorbed ATA rate (7-4.5%), which was associated with variations of Zeta potentials (−27.5 to −24.3 mV) and decrease in polymeric wall thickness and density.
Full text
Available for:
IJS, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the ...chronic mild stress model, some rats develop depression-like symptoms (including "anhedonia"), whereas others are stress resilient.
After 8 weeks of chronic mild stress, anhedonic rats reduced their sucrose intake by 55% (7%), whereas resilient rats did not. Acetylcholine-induced endothelium-dependent relaxation of norepinephrine-preconstricted mesenteric arteries was analyzed in nonstressed, anhedonic, and resilient rat groups.
Small resistance arteries from anhedonic rats were less sensitive to acetylcholine than those of the nonstressed and resilient groups (p = .029). Pathways of endothelium-dependent relaxation were altered in arteries from anhedonic rats. Nitric oxide (NO)-dependent relaxation and endothelial NO synthase expression were increased in arteries from anhedonic rats (0.235 0.039 arbitrary units and 155.7% 8.15%) compared with the nonstressed (0.135 0.012 arbitrary units and 100.0% 8.08%) and resilient (0.152 0.018 arbitrary units and 108.1% 11.65%) groups (p < .001 and p = .002, respectively). Inhibition of cyclooxygenase (COX) activity revealed increased COX-2-dependent relaxation in the anhedonic group. In contrast, endothelial NO synthase- and COX-independent relaxation to acetylcholine (endothelium-dependent hyperpolarization-like response) was reduced in anhedonic rats (p < .001). This was associated with decreased transcription of intermediate-conductance Ca-activated K channels.
Our findings demonstrate that depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed endothelium-dependent hyperpolarization-like relaxation despite up-regulation of the NO and COX-2-dependent pathways in rat mesenteric arteries. These changes could affect peripheral resistance and organ perfusion in major depression.
The cause of warming in the Southern Hemisphere during the most recent deglaciation remains a matter of debate. Hypotheses for a Northern Hemisphere trigger, through oceanic redistributions of heat, ...are based in part on the abrupt onset of warming seen in East Antarctic ice cores and dated to 18,000 years ago, which is several thousand years after high-latitude Northern Hemisphere summer insolation intensity began increasing from its minimum, approximately 24,000 years ago. An alternative explanation is that local solar insolation changes cause the Southern Hemisphere to warm independently. Here we present results from a new, annually resolved ice-core record from West Antarctica that reconciles these two views. The records show that 18,000 years ago snow accumulation in West Antarctica began increasing, coincident with increasing carbon dioxide concentrations, warming in East Antarctica and cooling in the Northern Hemisphere associated with an abrupt decrease in Atlantic meridional overturning circulation. However, significant warming in West Antarctica began at least 2,000 years earlier. Circum-Antarctic sea-ice decline, driven by increasing local insolation, is the likely cause of this warming. The marine-influenced West Antarctic records suggest a more active role for the Southern Ocean in the onset of deglaciation than is inferred from ice cores in the East Antarctic interior, which are largely isolated from sea-ice changes.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in ...mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclasts in vitro suggesting a role for septins in bone resorption. Attesting to this, conditional deletion of Sept9 in mice leads to elevated levels of trabecular bone and diminished femoral growth in vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Here we present a newly developed ice core gas-phase proxy that directly samples a component of the large-scale atmospheric circulation: synoptic-scale pressure variability. Surface pressure changes ...weakly disrupt gravitational isotopic settling in the firn layer, which is recorded in krypton-86 excess (.sup.86 Kr.sub.xs). The .sup.86 Kr.sub.xs may therefore reflect the time-averaged synoptic pressure variability over several years (site "storminess"), but it likely cannot record individual synoptic events as ice core gas samples typically average over several years. We validate .sup.86 Kr.sub.xs using late Holocene ice samples from 11 Antarctic ice cores and 1 Greenland ice core that collectively represent a wide range of surface pressure variability in the modern climate. We find a strong spatial correlation (r=-0.94, p<0.01) between site average .sup.86 Kr.sub.xs and time-averaged synoptic variability from reanalysis data. The main uncertainties in the analysis are the corrections for gas loss and thermal fractionation and the relatively large scatter in the data. Limited scientific understanding of the firn physics and potential biases of .sup.86 Kr.sub.xs require caution in interpreting this proxy at present. We show that Antarctic .sup.86 Kr.sub.xs appears to be linked to the position of the Southern Hemisphere eddy-driven subpolar jet (SPJ), with a southern position enhancing pressure variability.
Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a ...community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike.
PDF
