High-resolution proglacial lake records of pre-Little Ice Age glacier advance, northeast Greenland

Understanding Arctic glacier sensitivity is key to predicting future response to air temperature rise. Previous studies have used proglacial lake sediment records to reconstruct Holocene glacier advance–retreat patterns in South and West Greenland, but high‐resolution glacier records from High Arctic Greenland are scarce, despite the sensitivity of this region to future climate change. Detailed geochemical analysis of proglacial lake sediments close to Zackenberg, northeast Greenland, provides the first high‐resolution record of Late Holocene High Arctic glacier behaviour. Three phases of glacier advance have occurred in the last 2000 years. The first two phases (c. 1320–800 cal. a BP) occurred prior to the Little Ice Age (LIA), and correspond to the Dark Ages Cold Period and the Medieval Climate Anomaly. The third phase (c. 700 cal. a BP), representing a smaller scale glacier oscillation, is associated with the onset of the LIA. Our results are consistent with recent evidence of pre‐LIA glacier advance in other parts of the Arctic, including South and West Greenland, Svalbard, and Canada. The sub‐millennial glacier fluctuations identified in the Madsen Lake succession are not preserved in the moraine record. Importantly, coupled XRF and XRD analysis has effectively identified a phase of ice advance that is not visible by sedimentology alone. This highlights the value of high‐resolution geochemical analysis of lake sediments to establish rapid glacier advance–retreat patterns in regions where chronological and morphostratigraphical control is limited

Do intoxicated witnesses produce poor facial composite images?

The effect of alcohol intoxication on witness memory and performance has been the subject of research for some time, however, whether intoxication affects facial composite construction has not been investigated. Intoxication was predicted to adversely affect facial composite construction. Thirty-two participants were allocated to one of four beverage conditions consisting of factorial combinations of alcohol or placebo at face encoding, and later construction. Participants viewed a video of a target person and constructed a composite of this target the following day. The resulting images were presented as a full face composite, or a part face consisting of either internal or external facial features to a second sample of participants who provided likeness ratings as a measure of facial composite quality. Intoxication at face encoding had a detrimental impact on the quality of facial composites produced the following day, suggesting that alcohol impaired the encoding of the target faces. The common finding that external compared to internal features are more accurately represented was demonstrated, even following alcohol at encoding. This finding was moderated by alcohol and target face gender such that alcohol at face encoding resulted in reduced likeness of external features for male composite faces only. Moderate alcohol intoxication impairs the quality of facial composites, adding to existing literature demonstrating little effect of alcohol on line-up studies. The impact of intoxication on face perception mechanisms, and the apparent narrowing of processing to external face areas such as hair, is discussed in the context of alcohol myopia theory

Cortisol in hair measured in young adults - a biomarker of major life stressors?

<p>Abstract</p> <p>Background</p> <p>Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.</p> <p>Methods</p> <p>Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.</p> <p>Results</p> <p>Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.</p> <p>Conclusions</p> <p>These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.</p

Regional Holocene climate and landscape changes recorded in the large subarctic lake Torneträsk, N Fennoscandia

Understanding the response of sensitive Arctic and subarctic landscapes to climate change is essential to determine the risks of ongoing and projected climate warming. However, these responses will not be uniform in terms of timing and magnitude across the landscape because of site-specific differences in ecosystem susceptibility to climate forcing. Here we present a multi-proxy analysis of a sediment record from the 330-km2 lake Torneträsk to assess the sensitivity of the Fennoscandian subarctic landscape to climate change over the past ~ 9500 years. By comparing responses of this large-lake system to past climatic and environmental changes with those in small lakes in its catchment, we assessed when the magnitude of change was sufficient to affect an entire region rather than only specific sub-catchments that may be more sensitive to localized environmental changes such as, e.g., tree-line dynamics. Our results show three periods of regional landscape alteration with distinct change in sediment composition: i) landscape development following deglaciation and through the Holocene Thermal Maximum, ~ 9500–3400 cal yr BP; ii) increased soil erosion during the Little Ice Age (LIA); and iii) rapid change during the past century coincident with ongoing climate change. The gradual landscape development led to successive changes in the lake sediment composition over several millennia, whereas climate cooling during the late Holocene caused a rather abrupt shift occurring within ~ 100 years. However, this shift at the onset of the LIA (~ 750 cal yr BP) occurred > 2000 years later than the first indications for climate cooling recorded in small lakes in the Torneträsk catchment, suggesting that a critical ecosystem threshold was not crossed until the LIA. In contrast, the ongoing response to recent climate change was immediate, emphasizing the unprecedented scale of ongoing climate changes in subarctic Fennoscandia

Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn^®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity.</p> <p>Methods</p> <p>Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months.</p> <p>Results</p> <p>Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time.</p> <p>Conclusions</p> <p>IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.</p

Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

Given the immense significance of p53 restoration for anti-cancer therapy and that p53-activating molecules are in clinical trials, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of a novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in allosteric regulation of p53, whose targeting by small molecules RITA, PpIX and licofelone blocks the binding of two p53 inhibitors, MDM2 and MDMX, thereby restoring p53 function. Deletion and mutation analysis followed by molecular modeling and its thorough validation, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site in p53 induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators as targeted drugs. Our study provides a basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacopeia

Offspring Hormones Reflect the Maternal Prenatal Social Environment: Potential for Foetal Programming?

Females of many species adaptively program their offspring to predictable environmental conditions, a process that is often mediated by hormones. Laboratory studies have shown, for instance, that social density affects levels of maternal cortisol and testosterone, leading to fitness-relevant changes in offspring physiology and behaviour. However, the effects of social density remain poorly understood in natural populations due to the difficulty of disentangling confounding influences such as climatic variation and food availability. Colonially breeding marine mammals offer a unique opportunity to study maternal effects in response to variable colony densities under similar ecological conditions. We therefore quantified maternal and offspring hormone levels in 84 Antarctic fur seals (Arctocephalus gazella) from two closely neighbouring colonies of contrasting density. Hair samples were used as they integrate hormone levels over several weeks or months and therefore represent in utero conditions during foetal development. We found significantly higher levels of cortisol and testosterone (both P < 0.001) in mothers from the high density colony, reflecting a more stressful and competitive environment. In addition, offspring testosterone showed a significant positive correlation with maternal cortisol (P < 0.05). Although further work is needed to elucidate the potential consequences for offspring fitness, these findings raise the intriguing possibility that adaptive foetal programming might occur in fur seals in response to the maternal social environment. They also lend support to the idea that hormonally mediated maternal effects may depend more strongly on the maternal regulation of androgen rather than cortisol levels