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The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51 , an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function. [Display omitted] • Skeletal-muscle-specific S1P knockout mice have increased muscle mass • S1P negatively regulates mitochondrial respiration by increasing Mss51 expression • TGF-β1-driven Mss51 expression is controlled by S1P Mousa et al. show that site-1 protease (S1P) negatively regulates skeletal muscle mass and mitochondrial respiration. S1P inhibits respiration via its positive regulation of Mss51 expression. S1P depletion partially impairs TGF-β1-dependent Mss51 expression, implicating S1P in TGF-β1 signaling. These findings expand our understanding of the multi-faceted control of mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

Background and aims Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. Methods We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR = 51, Placebo = 52). Marijuana use was dichotomized into smoking (THC > 100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. Results The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7–9, even when controlling for MWC scores (week 7 Risk Difference (RD) = 0.11, p = 0.034; week 8 RD = 0.20, p = 0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD = 0.03, p = 0.380; week 11 RD = 0.07, p = 0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Conclusions Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. [ABSTRACT FROM AUTHOR]

Abstract: The Greenland Ice Sheet is a major component of the Arctic cryosphere and the magnitude of its response to future climate changes remains uncertain. Longer-term records of climate near the ice sheet margin provide information about natural climate variability and can be used to understand the causes of past changes in the Greenland Ice Sheet. As a proxy for Holocene climate near the ice sheet margin, we reconstruct the fluctuations of Bregne ice cap in the Scoresby Sund region of central east Greenland. Bregne is a small ice cap (2.5 km2 in area) and responds sensitively to summer temperatures. We employ a multi-proxy approach to reconstruct the ice cap fluctuations using geomorphic mapping, 10Be ages of boulders and bedrock and lake sediment records. Past extents of Bregne ice cap are marked by moraines and registered by sediments in downvalley lakes. 10Be ages of bedrock and boulders outboard of the moraines indicate that Bregne ice cap was within ∼250 m of its present-day limit by at least 10.7 ka. Multi-proxy data from sediments in Two Move lake, located downvalley from Bregne ice cap, indicate that the ice cap likely completely disappeared during early and middle Holocene time. Increasing magnetic susceptibility and percent clastic material from ∼6.5 to ∼1.9 cal ka BP in Two Move lake sediments suggest progressively colder conditions and increased snow accumulation on the highlands west of the lake. Laminated silt deposited at ∼2.6 cal ka BP and ∼1.9 cal ka BP to present registers the onset and persistence of Bregne ice cap during the late Holocene. 10Be ages of boulders on an unweathered, unvegetated moraine in the Bregne ice cap forefield range from 0.74 to 9.60 ka. The youngest 10Be age (0.74 ka) likely represents the age of the moraine whereas older ages may be due to 10Be inherited from prior periods of exposure. This late Holocene moraine marks the second largest advance of the ice cap since deglaciation of the region at the end of the last ice age. The oldest moraine in the forefield dates to ≤2.6 cal ka BP. The fluctuations of Bregne ice cap were likely influenced by Northern Hemisphere summer insolation throughout the Holocene and abrupt late Holocene cold events. [Copyright &y& Elsevier]

Abstract: Although Greenland ice core records register relatively stable Holocene climate conditions, the lower elevation margins of the Greenland Ice Sheet (GrIS) experienced significant Holocene fluctuations. These fluctuations include ice sheet recession during the Holocene Thermal Maximum (9–5 ka) and advance during the Little Ice Age (LIA; ∼A.D. 1350–1880). Determining the extent and timing of these fluctuations is important for understanding the response of the GrIS to interglacial climate conditions both warmer and colder than at present and for developing accurate ice sheet models. Sets of moraines marking past extents of the southwestern GrIS margin occur in the Kangerlussuaq region. We focus on the Ørkendalen moraines, a prominent moraine set located within 2 km of the modern ice margin and just outboard of the LIA moraines. We present the first 10Be ages of the Ørkendalen moraines indicating they were deposited at 6.8 ± 0.3 ka. The geomorphic relationship between the Ørkendalen and LIA moraines indicates that the ice sheet margin was inboard of its Ørkendalen extent between ∼6.8 ka and the culmination of the LIA. The age of the Ørkendalen moraines provides an important constraint on the extent of the southwestern GrIS during the middle Holocene. [Copyright &y& Elsevier]

Abstract: This paper is the first to summarize research on fluctuations of local glaciers in Greenland (e.g. ice caps and mountain glaciers independent of the Greenland Ice Sheet) during latest Pleistocene and Holocene time. In contrast to the extensive data available for fluctuations of the Greenland Ice Sheet, surprisingly little data exist to constrain local glacier extents. Much of the available research was conducted prior to wide-spread use of AMS radiocarbon dating and the advent of surface-exposure and luminescence dating. Although there is a paucity of data, generally similar patterns of local glacier fluctuations are observed in all regions of Greenland and likely reflect changes in paleoclimate, which must have influenced at least the margins of the Inland Ice. Absolute-age data for late-glacial and early Holocene advances of local glaciers are reported from only two locations: Disko (island) and the Scoresby Sund region. Subsequent to late-glacial or early Holocene time, most local glaciers were smaller than at present or may have disappeared completely during the Holocene Thermal Maximum. In general, local glacier advances that occurred during Historical time (1200–1940 AD) are the most extensive since late-glacial or early Holocene time. Historical documents and more recent aerial photographs provide useful information about local glacier fluctuations during the last ∼100 yrs. In all but one area (North Greenland), local glaciers are currently receding from Historical extents. [Copyright &y& Elsevier]

Abstract: Thirty-eight new cosmogenic (10Be) exposure ages from the Scoresby Sund region of east Greenland indicate that prominent moraine sets deposited by mountain glaciers date from 780 to 310yr, approximately during the Little Ice Age, from 11 660 to 10 630yr, at the end of the Younger Dryas cold interval or during Preboreal time, and from 13 010 to 11 630yr, during lateglacial time. Equilibrium line altitudes (ELAs) interpreted from lateglacial to Early Holocene moraines indicate summertime cooling between ∼3.9 and 6.6°C relative to today''s value, much less than the extreme Younger Dryas cooling registered by Greenland ice cores (mean-annual temperatures of ∼15°C colder than today''s value). This apparent discrepancy between paleotemperature records supports the contention that Younger Dryas cooling was primarily a wintertime phenomenon. 10Be ages of lateglacial and Holocene moraines show that mountain glaciers during the Little Ice Age were more extensive than at any other time since the Early Holocene Epoch. In addition, 10Be ages of lateglacial moraines show extensive reworking of boulders with cosmogenic nuclides inherited from prior periods of exposure, consistent with our geomorphic observations and cosmogenic-exposure dating studies in other Arctic regions. [Copyright &y& Elsevier]

Abstract: The Greenland Ice Sheet is undergoing dynamic changes that will have global implications if they continue into the future. In this regard, an understanding of how the ice sheet responded to past climate changes affords a baseline for anticipating future behavior. Small, independent ice caps adjacent to the Greenland Ice Sheet (hereinafter called “local ice caps”) are sensitive indicators of the response of Greenland ice-marginal zones to climate change. Therefore, we reconstructed late Holocene ice-marginal fluctuations of the local Istorvet ice cap in east Greenland, using radiocarbon dates of subfossil plants, 10Be dates of surface boulders, and analyses of sediment cores from both threshold and control lakes. During the last termination, the Istorvet ice cap had retreated close to its maximum Holocene position by ∼11,730 cal yr BP. Radiocarbon dates of subfossil plants exposed by recent recession of the ice margin indicate that the Istorvet cap was smaller than at present from AD 200 to AD 1025. Sediments from a threshold lake show no glacial input until the ice cap advanced to within 365 m of its Holocene maximum position by ∼AD 1150. Thereafter the ice cap remained at or close to this position until at least AD 1660. The timing of this, the most extensive of the Holocene, expansion is similar to that recorded at some glaciers in the Alps and in southern Alaska. However, in contrast to these other regions, the expansion in east Greenland at AD 1150 appears to have been very close to, if not at, a maximum Holocene value. Comparison of the Istorvet ice-cap fluctuations with Holocene glacier extents in Southern Hemisphere middle-to-high latitude locations on the Antarctic Peninsula and in the Andes and the Southern Alps suggests an out-of-phase relationship. If correct, this pattern supports the hypothesis that a bipolar see-saw of oceanic and/or atmospheric circulation during the Holocene produced asynchronous glacier response at some localities in the two polar hemispheres. [Copyright &y& Elsevier]

Elucidating the timing and regional extent of abrupt climate events during the last glacial-interglacial transition (∼18–11.5 ka) is critical for identifying spatial patterns and mechanisms responsible for large-magnitude climate events. The record of climate change in the Southern Hemisphere during this time period, however, remains scarce and unevenly distributed. We present new geomorphic, chronological, and equilibrium line altitude (ELA) data from a climatically sensitive mountain glacier at Monte San Lorenzo (47°S), Central Patagonia. Twenty-four new cosmogenic 10 Be exposure ages from moraines provide a comprehensive glacial record in the mid-latitudes of South America, which constrain the timing, spatial extent and magnitude of glacial fluctuations during the Antarctic Cold Reversal (ACR, ∼14.5–12.9 ka). Río Tranquilo glacier advanced and reached a maximum extent at 13.9 ± 0.7 ka. Three additional inboard moraines afford statistically similar ages, indicating repeated glacier expansions or marginal fluctuations over the ACR. Our record represents the northernmost robust evidence of glacial fluctuations during the ACR in southern South America, documenting not only the timing of the ACR maximum, but also the sequence of glacier changes within this climate event. Based on ELA reconstructions, we estimate a cooling of >1.6–1.8 °C at the peak of the ACR. The Río Tranquilo record along with existing glacial reconstructions from New Zealand (43°S) and paleovegetation records from northwestern (41°S) and central-west (45°S) Patagonia, suggest an uniform trans-Pacific glacier-climate response to an ACR trigger across the southern mid-latitudes. We posit that the equatorial migration of the southern westerly winds provides an adequate mechanism to propagate a common ACR signal across the Southern Hemisphere. [ABSTRACT FROM AUTHOR]

Reconstructions of Holocene lake water isotopic composition based upon subfossil aquatic organic material offer new insights into Arctic climate. We present quantitative estimates of warmth during the Holocene Thermal Maximum in northwest Greenland, inferred from oxygen isotopes of chironomid head capsules and aquatic moss preserved in lake sediments. δ 18 O values of chironomids from surface sediments of multiple Greenland lakes indicate that these subfossil remains record the δ 18 O values of the lake water in which they grow. Our lake water δ 18 O reconstruction is supported by downcore agreement with δ 18 O values in aquatic moss and chironomid remains. δ 18 O of both organic materials from Secret Lake decrease after 4 ka (ka = thousands of years ago) by 3‰ into the Neoglacial. We argue that lake water at Secret Lake primarily reflects precipitation δ 18 O values, which is strongly correlated with air temperature in NW Greenland, and that this signal is biased towards summer and early autumn conditions. Other factors may have influenced Secret Lake δ 18 O values through the Holocene, including evaporation of lake water and changing seasonality and source of precipitation. The maximum early Holocene summer and early autumn-biased temperature anomaly at Secret Lake is 2.5–4 °C warmer than present from 7.7 (the beginning of our record) to ∼6 ka. The maximum late Holocene cold anomaly (which includes the Little Ice Age) is 1.5–3 °C colder than present. These ranges of possible temperature anomalies reflect uncertainty in the δ 18 O – temperature relationship for precipitation at the study site through the Holocene. [ABSTRACT FROM AUTHOR]

Improving the late Quaternary paleoclimate record through climate interpretations of low-latitude glacier length changes advances our understanding of past climate change events and the mechanisms for past, present, and future climate change. Paleotemperature reconstructions at low-latitude glaciers are uniquely fruitful because they can provide both site-specific information and enhanced understanding of regional-scale variations due to the structure of the tropical atmosphere. We produce Little Ice Age (LIA) and Younger Dryas (YD) paleoclimate reconstructions for the Huancané outlet glacier of the Quelccaya Ice Cap (QIC) and low-latitude southern hemisphere regional sea surface temperatures (SSTs) using a coupled ice-flow and energy balance model. We also model the effects of long-term changes in the summit temperature and precipitiation rate and the effects of interannual climate variability on the Huancané glacier length. We find temperature to be the dominant climate driver of glacier length change. Also, we find that interannual climate variability cannot adequately explain glacier advances inferred from the geomorphic record, necessitating that these features were formed during past colder climates. To constrain our LIA reconstruction, we incorporate the QIC ice core record, finding a LIA air temperature cooling at the ice cap of between ∼0.7 °C and ∼1.1 °C and ∼0.4 °C and regional SSTs cooling of ∼0.6 °C. For the YD paleoclimate reconstructions, we propose two limits on the precipitation rate, since the ice core record does not extend into the Pleistocene: 1) the precipitation rate scales with the Clausius-Clapeyron relationship (upper limit on cooling) and 2) the precipitation rate increases by 40% (lower limit on cooling), which is an increase about twice as great as the regional increases realized in GCM simulations for the period. The first limit requires ∼1.6 °C cooling in ice cap air temperatures and ∼0.9 °C cooling in SSTs, and the second limit requires ∼1.0 °C cooling in ice cap air temperatures and ∼0.5 °C cooling in SSTs. Our temperature reconstructions are in good agreement with the magnitude and trend of GCM simulations that incorporate the forcing mechanisms hypothesized to have caused these climate change events. [ABSTRACT FROM AUTHOR]

Tropical mountain environments, such as the Rwenzori Mountains in equatorial Africa, are thought to be particularly sensitive to climate change. Ongoing warming in the Rwenzori is impacting local environments and communities through glacial retreat, fires, and flooding. Paleoclimate reconstructions from elsewhere in Africa suggest considerable warming accompanied glacier retreat during the last glacial termination, from ∼21 thousand years before present (ka) through the early to mid-Holocene. Quantifying these changes has been difficult but could help to assess future impacts in the Rwenzori. Here, we present a ∼21 thousand-year (kyr) temperature reconstruction based on the relative abundance of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from Lake Mahoma (2,990 m above sea level; m asl) in the Rwenzori Mountains, Uganda. Our record, paired with existing Rwenzori glacial moraine 10Be exposure ages, suggests that deglacial warming and glacial retreat began by ∼20 ka and accelerated at ∼18–18.5 ka. The timing of the onset of rapid warming matches the timing of the post-glacial rise in radiative forcing from atmospheric greenhouse gases (GHGs) from Antarctic ice cores (Brook et al., 1996; Marcott et al., 2014; Monnin et al., 2004; Schilt et al., 2010). Our temperature reconstruction registers ∼4.9 °C warming from the Last Glacial Maximum (LGM) to the late Holocene. This increase is larger than the average ∼2-4 °C warming observed in records from lower elevation sites in tropical East Africa, but similar to that observed at other high-elevation sites in this region. The increased warming at higher elevations thus confirms that the temperature lapse rate steepened during the LGM over this region. Our results also indicate ∼3 °C of warming during the mid-Holocene relative to the late Holocene. This suggests that the freezing-level height rose above Rwenzori summit elevations at that time, likely causing complete deglaciation of the Rwenzori Mountains from ∼5 to 7 ka. The mid-Holocene is thus a potential analog for the glacial and environmental changes that these mountains are likely to experience in the coming decades. Overall, the timing and magnitude of temperature change observed in our record has important implications for climate model projections of future warming in tropical Africa. • We produce a 21 kyr temperature record from alpine Lake Mahoma, Uganda. • Rwenzori glaciers and vegetation are very sensitive to past temperature change. • ∼3 °C warming during middle Holocene caused complete deglaciation in Rwenzori. • Regional temperature records indicate a steeper tropical lapse rate during the LGM. • Tropical lapse rate shoaled and stabilized during the middle and late Holocene. [ABSTRACT FROM AUTHOR]

Abstract: We use a simple model to analyse the relationship between ice core temperature proxy data and global ice volume/eustatic sea-level data over the last glacial cycle (LGC). By allowing the temperature forcing to be a mix of Greenlandic and Antarctic signals we optimise the proportion of this mixing to fit sea-level data. We find that sea-level forcing is best represented by a mix of Antarctic and Greenlandic temperature signals through the whole glacial cycle. We suggest that a distinct bipolar switch occurs which links eustatic sea-level more closely with the Antarctic-like variability during the glacial period (MIS 4, 3 and 2) and more closely to the Greenland-like variability during the last termination (TI) and the interglacial periods (Holocene and MIS 5). This switch may be caused by the spatio-temporal distribution of ice sheet collapse perhaps linked to glacial to interglacial changes in deep water distribution in the ocean, which in turn drive changes in pole-ward heat and moisture transport. [Copyright &y& Elsevier]

Shrinking glaciers, melting permafrost, and reduced sea ice all indicate rapid contraction of the Arctic cryosphere in response to present-day climate warming, a trajectory that is expected to continue, if not accelerate. The reaction of the Arctic cryosphere to past periods of climate variation can afford insight into its present and future behavior. Here, we examine a ∼12,000 year record of glacier fluctuations and meltwater variation associated with the Renland Ice Cap, East Greenland, that extends from the early Holocene thermal optimum through the cooling of the Little Ice Age to present. Sediment records from glacially fed lakes indicate rapid early Holocene deglaciation, with ice extent likely slightly smaller than at present by ∼9500 yr BP. Glacial activity resulted in occasional deposition of rock flour in the studied lakes in the early Holocene until at least ∼7500 yr BP. Rock flour is absent for much of the period ∼7000-4000 yr BP, suggesting ice extent generally was smaller than at present. However, thin layers of blue-gray clay throughout this period may indicate millennial-scale ice expansions, with Renland Ice Cap briefly reaching extents during cold phases that may have been similar to today. Glacial sediment deposition occurred again in the late Holocene at ∼3200–3400 yr BP and was followed by a brief glacial episode at ∼1340 yr BP and then a major event beginning shortly after ∼1050 yr BP. We infer that rock flour deposition in the lakes in the last millennium corresponds with advance of Renland glaciers to their Little Ice Age positions, marked by a fresh, gray drift limit. Radiocarbon dates of in situ plant remains adjacent to the present ice cap indicate a short relatively warm period ∼500 yr ago, when ice was within its AD 2011 limit, followed by glacier readvance. The general pattern of ice fluctuations in Renland is similar to that at other ice caps in the region, but also has important differences, including the preservation of a possible mid-Holocene record at times when lower-elevation ice caps in the Scoresby Sund region may have been absent. This finding reinforces the concept that examination of multiple geographic and geomorphologic settings is necessary for a full understanding of ice variations in a region. • Sediments from glacially fed lakes constrain the Holocene history of Renland Ice Cap. • Ice extent was similar to or smaller than at present by ∼10,000 yr BP. • Millennial-scale glacier fluctuations occurred throughout the Holocene. • Examination of multiple geographic settings is necessary for a full understanding of ice variations in a region. [ABSTRACT FROM AUTHOR]

To put recent Greenland Ice Sheet (GrIS) ice loss into a longer-term context, we must understand its behavior during late-glacial and Early Holocene warming. Previous results seem to suggest that there is a large contrast in the timing of deglaciation between South and Southeast Greenland. However, because of lack of available data, in particular in Southeast Greenland, it is difficult to assess how the ice sheet responded to major late-glacial and Early Holocene climate changes. In this study, we use 41 new 10Be ages to constrain the deglaciation chronology in 12 new locations from the coast to the present ice margin in South and Southeast Greenland. We find that South Greenland (south of 61.5°N) deglaciated between ∼14.8 and 11.9 ka, whereas Southeast Greenland (61.5°N to 68.2°N) deglaciated between ∼11.4 and 11.3 ka. The deglaciation of the coastal, low-intermediate topography in South Greenland coincides with increased air surface temperatures during the Bølling-Allerød with fjords continuing to deglaciate into the Early Holocene. In contrast, the ice sheet persisted at the coast until the late-glacial and Early Holocene in Southeast Greenland, likely because of increased precipitation in the high alpine topography and fjord geometry and bathymetry (e.g. width of fjords and presence of sills). This multi-phased deglaciation demonstrates a contrasting response of the southern GrIS to changes in climate and variations in topographic setting, and that the spatial deglaciation of the GrIS was complex and likely did not respond to a single external climate forcing. • Deglaciation began in South Greenland by 14.8 ka coeval with rising air temperature. • Warm Atlantic water likely drove deglaciation during the Younger Dryas. • Ice retreated from Southeast Greenland coast by 11.3 ka when air temperatures rose. • Evidence of a Neoglacial advance occurs in Southeast Greenland by ∼1.9 ka. • Local climate, topography and fjord geometry/bathymetry likely mediated ice retreat. [ABSTRACT FROM AUTHOR]