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"Zimmermann, Andreas"
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Population dynamics and socio-spatial organization of the Aurignacian: Scalable quantitative demographic data for western and central Europe
Demographic estimates are presented for the Aurignacian techno-complex (~42,000 to 33,000 y calBP) and discussed in the context of socio-spatial organization of hunter-gatherer populations. Results of the analytical approach applied estimate a mean of 1,500 persons (upper limit: 3,300; lower limit: 800) for western and central Europe. The temporal and spatial analysis indicates an increase of the population during the Aurignacian as well as marked regional differences in population size and density. Demographic increase and patterns of socio-spatial organization continue during the subsequent early Gravettian period. We introduce the concept of Core Areas and Extended Areas as informed analytical spatial scales, which are evaluated against additional chronological and archaeological data. Lithic raw material transport and personal ornaments serve as correlates for human mobility and connectedness in the interpretative framework of this study. Observed regional differences are set in relation with the new demographic data. Our large-scale approach on Aurignacian population dynamics in Europe suggests that past socio-spatial organization followed socially inherent rules to establish and maintain a functioning social network of extremely low population densities. The data suggest that the network was fully established across Europe during the early phase of the Gravettian, when demographic as well as cultural developments peaked.
Journal Article
High-resolution thickness maps of corrosion using SH1 guided wave tomography
Quantifying corrosion damage is vital for the petrochemical industry, and guided wave tomography can provide thickness maps of such regions by transmitting guided waves through these areas and capturing the scattering information using arrays. The dispersive nature of the guided waves enables a reconstruction of wave velocity to be converted into thickness. However, existing approaches have been shown to be limited in in-plane resolution, significantly short of that required to accurately image a defect target of three times the wall thickness (i.e. 3 T) in each in-plane direction. This is largely due to the long wavelengths of the fundamental modes commonly used, being around 4 T for both A0 and S0 at the typical operation points. In this work, the suitability of the first-order shear-horizontal guided wave mode, SH1, has been investigated to improve the resolution limit. The wavelength at the desired operating point is significantly shorter, enabling an improvement in resolution of around 2.4 times. This is first verified by realistic finite-element simulations and then validated by experimental results, confirming the improved resolution limit can now allow defects of maximum extent 3T-by-3T to be reliably detected and sized, i.e. a long-pursued goal of guided wave tomography has been achieved.
Journal Article
The geroprotective potential of chalcones
Aging is the most important risk factor for multiple pathologies including cardiovascular, neoplastic, metabolic and neurodegenerative diseases. Potential geroprotective strategies involve lifestyle-related, nutritional and pharmacological interventions. Recently, chalcones, a subgroup of secondary plant metabolites, have gained attention. 4,4’-dimethoxychalcone was the first chalcone to be shown to mediate geroprotection and lifespan extension across different species. Several other chalcones also exert anti-aging effects at the cellular and organismal levels. Defined mechanistic routes that are causally involved in these protective effects have been delineated. Here, we summarize current evidence supporting the potential of 4,4’-dimethoxychalcone and other chalcones as geroprotective agents.
Aging is driven by biological processes that can potentially be targeted by pharmacological interventions to delay its onset and extend healthspan. Here, the authors show the growing evidence supporting chalcones, a subgroup of secondary plant metabolites, as novel geroprotective agents
Journal Article
Yeast as a tool to identify anti-aging compounds
In the search for interventions against aging and age-related diseases, biological screening platforms are indispensable tools to identify anti-aging compounds among large substance libraries. The budding yeast, Saccharomyces cerevisiae, has emerged as a powerful chemical and genetic screening platform, as it combines a rapid workflow with experimental amenability and the availability of a wide range of genetic mutant libraries. Given the amount of conserved genes and aging mechanisms between yeast and human, testing candidate anti-aging substances in yeast gene-deletion or overexpression collections, or de novo derived mutants, has proven highly successful in finding potential molecular targets. Yeast-based studies, for example, have led to the discovery of the polyphenol resveratrol and the natural polyamine spermidine as potential anti-aging agents. Here, we present strategies for pharmacological anti-aging screens in yeast, discuss common pitfalls and summarize studies that have used yeast for drug discovery and target identification.
Journal Article
Targeting the Mitochondria-Proteostasis Axis to Delay Aging
Human life expectancy continues to grow globally, and so does the prevalence of age-related chronic diseases, causing a huge medical and economic burden on society. Effective therapeutic options for these disorders are scarce, and even if available, are typically limited to a single comorbidity in a multifaceted dysfunction that inevitably affects all organ systems. Thus, novel therapies that target fundamental processes of aging itself are desperately needed. In this article, we summarize current strategies that successfully delay aging and related diseases by targeting mitochondria and protein homeostasis. In particular, we focus on autophagy, as a fundamental proteostatic process that is intimately linked to mitochondrial quality control. We present genetic and pharmacological interventions that effectively extend health- and life-span by acting on specific mitochondrial and pro-autophagic molecular targets. In the end, we delve into the crosstalk between autophagy and mitochondria, in what we refer to as the mitochondria-proteostasis axis, and explore the prospect of targeting this crosstalk to harness maximal therapeutic potential of anti-aging interventions.
Journal Article
Large scale and regional demographic responses to climatic changes in Europe during the Final Palaeolithic
The European Final Palaeolithic witnessed marked changes in almost all societal domains. Despite a rich body of evidence, our knowledge of human palaeodemographic processes and regional population dynamics still needs to be improved. In this study, we present regionally differentiated population estimates for the Greenland Interstadial 1d-a (GI-1d-a; 14-12.7 ka cal BP) and the Greenland Stadial 1 (GS-1; 12.7-11.6 ka cal BP) for Southern, Western, Northern and Central Europe. The data were obtained by applying the Cologne Protocol, a geostatistical approach for estimating prehistoric population size and density, to a newly compiled dataset of Final Palaeolithic sites. On a large spatio-temporal scale and compared to preceding Upper Palaeolithic phases, areas north of the Alps become the dominant demographic growth area for the first time since the dispersal of anatomically modern humans into Europe. At smaller scales, we observe divergent regional trends, with a conspicuous lack of archaeological evidence appearing in previously occupied areas of central France and Germany. Our study also shows that during the Final Palaeolithic, the climatic cooling of GS-1 coincides with a pronounced population decline in most parts of the study area. An apparent increase in population density occurs only in north-eastern Central Europe and north-eastern Italy. Our estimates suggest that the total population was reduced by half. Similar results, with a relationship between decreasing temperatures and decreasing populations, have already been observed for the late phase of the Gravettian, when populations were reduced to only one third of those estimated for the early phase. Yet, in contrast to the collapse of local populations during the late Gravettian, the increase in population densities in Central Europe during GS-1 indicates population movements eastwards, possibly in response to deteriorating climatic conditions, particularly in western regions during the Younger Dryas.
Journal Article
Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion
Treatment to restore sinus rhythm among patients with atrial fibrillation (AF) has limited long-term success rates. Gene expression profiling may provide new insights into AF pathophysiology.
To identify biomarkers and improve our understanding of AF pathophysiology by comparing whole blood gene expression before and after electrical cardioversion (ECV).
In 46 patients with persistent AF that underwent ECV, whole blood samples were collected 1-2 hours before and 4 to 6 weeks after successful cardioversion. The paired samples were sent for microarray and plasma biomarker comparison.
Of 13,942 genes tested, expression of SLC25A20 and PDK4 had the strongest associations with AF. Post-cardioversion, SLC25A20 and PDK4 expression decreased by 0.8 (CI 0.7-0.8, p = 2.0x10-6) and 0.7 (CI 0.6-0.8, p = 3.0x10-5) fold respectively. Median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations decreased from 127.7 pg/mL to 44.9 pg/mL (p = 2.3x10-13) after cardioversion. AF discrimination models combining NT-proBNP and gene expression (NT-proBNP + SLC25A20 area under the curve = 0.88, NT-proBNP + PDK4 AUC = 0.86) had greater discriminative capacity as compared with NT-proBNP alone (AUC = 0.82). Moreover, a model including NT-proBNP, SLC25A20 and PDK4 significantly improved AF discrimination as compared with other models (AUC = 0.87, Net Reclassification Index >0.56, p<5.8x10-3). We validated the association between SLC25A20 and PDK4 with AF in an independent sample of 17 patients.
This study demonstrates that SLC25A20, PDK4, and NT-proBNP have incremental utility as biomarkers discriminating AF from sinus rhythm. Elevated SLC25A20 and PDK4 expression during AF indicates an important role for energy metabolism in AF.
Journal Article
3,4‐Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB
Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health‐promoting and longevity‐extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3,4‐dimethoxychalcone (3,4‐DC), among a library of polyphenols. When added to several different human cell lines, 3,4‐DC induced the deacetylation of cytoplasmic proteins and stimulated autophagic flux. At difference with other well‐characterized CRMs, 3,4‐DC, however, required transcription factor EB (TFEB)‐ and E3 (TFE3)‐dependent gene transcription and mRNA translation to trigger autophagy. 3,4‐DC stimulated the translocation of TFEB and TFE3 into nuclei both
in vitro
and
in vivo
, in hepatocytes and cardiomyocytes. 3,4‐DC induced autophagy
in vitro
and in mouse organs, mediated autophagy‐dependent cardioprotective effects, and improved the efficacy of anticancer chemotherapy
in vivo
. Altogether, our results suggest that 3,4‐DC is a novel CRM with a previously unrecognized mode of action.
Synopsis
From a library of polyphenols and polyamines, the 3,4‐dimethoxychalcone (3,4‐DC) was screened and identified as a caloric restriction mimetic (CRM) that induces autophagy through TFEB and TFE3 and results in cardioprotection and improved efficacy of anticancer chemotherapy in mice.
3,4‐DC induces all hallmarks of caloric restriction mimicry, i.e. the combination of autophagy, reduced protein acetylation and absence of toxicity.
3,4‐DC induces autophagy in a TFEB‐ and TFE3‐regulated, transcription and translation‐dependent manner.
3,4‐DC causes cardioprotection and enhances anticancer effects of chemotherapy in an autophagy‐dependent fashion
in vivo
in mice.
Graphical Abstract
From a library of polyphenols and polyamines, the 3,4‐dimethoxychalcone (3,4‐DC) was screened and identified as a caloric restriction mimetic (CRM) that induces autophagy through TFEB and TFE3 and results in cardioprotection and improved efficacy of anticancer chemotherapy in mice.
Journal Article
Process options for the recovery of a pentosan-enriched fraction from wheat-based bioethanol thin stillage
AimStillage, the main residue from cereal-based bioethanol production, offers a great potential for the recovery of pentosan-type carbohydrates. Therefore, potential process options for the recovery of pentosans from bioethanol thin stillage are investigated and their basic feasibility is demonstrated on a laboratory scale.FindingsThe main result of this work is the development of a three-stage process for pentosan recovery, including solid–liquid separation, pentosan solubilisation and purification. The pentosan content of the thin stillage used here was determined to be about 14% related to dry matter (DM). By means of solid–liquid separation, these pentosans accumulate in the liquid phase (up to 80%), while the remainder (about 20%) is found in the solid phase. Solubilisation of these insoluble pentosans was achieved by using either a hydrothermal, an alkaline or an enzymatic treatment. Here, the results indicate a maximum solubilisation yield of 90% with a hydrothermal treatment using liquid hot water at 180 °C. Ultrafiltration and precipitation are investigated for purification. The most promising process option in this study is solid–liquid separation followed by ultrafiltration. In this case, the total pentosan yield is assessed to be about 48% (based on thin stillage) with a final pentosan concentration of about 30%DM.
Journal Article