Biology subjects

Keller, M.

Publications and source records attributed to Keller, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Sex-specific role of epigenetic modification of a leptin upstream enhancer in the adipose tissue

ObjectiveMaternal hormonal status can have long-term effects on offspring metabolic health, likely regulated via epigenetic mechanisms. We elucidated the effect of maternal thyroid hormones on epigenetic regulation of Leptin (Lep) transcription in adipose tissue (AT) and investigated the role of DNA methylation at a Lep upstream enhancer (UE) in adipocyte biology. MethodsPregnant mice were treated with Triiodothyronine (T3). Offspring body composition and adipose tissue were analysed at 6 months (treatment: N = 8, control: N = 12). DNA methylation at the Lep UE and Lep mRNA levels in gonadal white adipose tissue (gWAT) and leptin serum levels were measured. The Lep UE was hypomethylated in murine preadipocytes using a dCas9-SunTag-TET1 system, followed by differentiation. In human visceral AT samples (N = 52) from the Leipzig Obesity BioBank (LOBB) LEP UE methylation and LEP mRNA levels were assessed alongside leptin serum levels and correlated with body fat percentage. Causal relationships were explored using mediation analysis. ResultsHigh maternal T3 levels reduced offspring body weight, total fat, and gWAT mass. Female offspring of T3-treated mothers showed lower Lep mRNA levels and higher Lep UE methylation compared to controls. CRISPR/dCas9 editing reduced Lep UE methylation by [~]20% in preadipocytes without altering Lep expression or lipid accumulation after differentiation. In humans, a mediation of sex-specific difference in body fat percentage via Lep UE methylation was found. ConclusionMaternal thyroid hormones might affect offspring gWAT Lep expression in a sex-specific manner, potentially driven by DNA methylation at the Lep UE, influencing body fat percentage.

genetics↗

bioRxiv2024

On the specificity of manual triggers of autonomic nervous system responses using osteopathic cranial manipulative medicine

Significant autonomic nervous system responses to a specific osteopathic intervention, the cranial vault hold (CVH), have recently been demonstrated in forehead skin blood volume changes, heart rate, and respiration frequencies. The specificity of the CVH-intervention-related autonomic responses yet requires differentiation. Thus, we compared autonomic responses to CVH with responses to compression of the fourth ventricle (CV4) and to two corresponding SHAM conditions. Analysis of frequencies and amplitudes for changes in skin blood volume and respiration in low (LF; 0.05 - 0.12 Hz), intermediate (IM; 0.12 - 0.18 Hz), and high (HF; 0.18 - 0.4 Hz) frequency bands, and metrics of heartrate variability revealed significant decreases in LF range (from 0.12 to 0.10 Hz), increased LF and decreased IM durations, and increased skin blood volume amplitudes in response to CVH, but no significant skin blood volume responses to any of the control interventions. Ratio changes for respiration and skin blood volume frequencies approximately at 3:1 during CVH, remained unchanged in all other interventions. Heart rate decreased across conditions, indicating an increase in parasympathetic tone. This was also indicated by a significant increase in root mean of squared successive difference following CV4. We incurred that rhythmic response patterns in the LF and IM bands only appeared in CVH. This suggests specific physiological responses to CVH warranting further investigation by studying e.g., responses to CVH in physical or mental health disorders with autonomic involvement.

physiology↗

bioRxiv2024

Circulation of West Nile Virus and Usutu Virus in Birds in Germany, 2021 and 2022.

BackgroundUsutu virus (USUV) and West Nile virus (WNV) are zoonotic arthropod-borne orthoflaviviruses. The enzootic transmission cycles of both include Culex mosquitoes as vectors and birds as amplifying hosts. For more than ten years, these viruses have been monitored in birds in Germany by a multidisciplinary network. While USUV is present nationwide, WNV used to be restricted to the central-east. MethodsIn 2021 and 2022, over 2300 live bird blood samples and organs from over 3000 deceased birds were subjected to molecular and serological analysis regarding presence of WNV and USUV. The samples were collected at sites all over Germany. ResultsCirculation of both viruses increased in 2022. For USUV, the nationwide presence of lineages Africa 3 and Europe 3 reported in previous years was confirmed. Lineage Europe 2, formerly restricted to the German east, was able to expand westward. Nonetheless, USUV neutralizing antibody (nAb) detection rates remained low (< 9%). 2021 and 2022 were characterized by stable enzootic circulation of WNV lineage 2, dominated by one previously identified subcluster (95% of generated sequences). In 2022, more than 20% of birds in the endemic region in eastern Germany carried nAb against WNV. Serological data also indicate expanding WNV circulation west and south of the known hotspots in Germany. ConclusionsUSUV circulates enzootically nationwide. Emergence of WNV at several new locations in Germany with a potential increase in human infections may be imminent. In this context, wild bird monitoring serves as a capable early-warning system in a One Health setting.

microbiology↗

bioRxiv2024

Lysosomal signalling pathways influence heart rhythm, and regulate atrial function

In the heart, endogenous nicotinic acid adenine dinucleotide phosphate (NAADP) triggers lysosomal calcium (Ca2+) release to augment sarcoplasmic reticulum (SR) Ca2+ sequestration, producing larger Ca2+ transients. However, the role of lysosomal Ca2+ signals in pacemaker activity, a distinct Ca2+-operated function of the sinoatrial node (SAN), or in the atrial myocardium has not been investigated. Pharmacological or genetic ablation of the NAADP pathway inhibits the spontaneous beating rate response to beta-adrenergic stimulation in intact SAN. We found intracellular signaling microdomains between lysosomes and neighboring SR or mitochondria in mouse, and goat tissue. The spatial relationship between lysosomes and other Ca2+-handling organelles are altered in goat atrial fibrillation. Furthermore, we demonstrate atrial myocytes produce cAMP in response to lysosomal signaling, adding a novel trigger for cyclic nucleotide signaling. Our findings support the hypothesis that lysosomal Ca2+ signaling contributes to regulation of cardiomyocyte cAMP levels and pacemaker activity.

physiology↗

bioRxiv2024

A plant-specific clade of serine/arginine-rich proteins regulates RNA splicing homeostasis and thermotolerance in tomato

High temperatures cause heat stress (HS), which has negative effects on plant growth and development and affects many cellular processes including pre-mRNA splicing. In tomato plants the splicing profile of many of genes is altered under HS, including that of HSFA2, a central transcriptional regulator of thermotolerance. To identify the core splicing regulators of HS-sensitive alternative splicing, we used HSFA2 as bait and identified two plant-specific members of the serine/arginine-rich family of splicing factors, namely RS2Z35 and RS2Z36, that inhibit HSFA2 intron splicing. Single and double CRISPR mutants of these proteins show dysregulated splicing of many genes and exhibit lower basal and acquired thermotolerance. Individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) of tomato leaves revealed that the majority of HS-sensitive alternatively spliced RNAs are bound by RS2Z35 and RS2Z36 and this interaction occurs at purine-rich RNA motifs. Phenotypic and transcriptome analyses revealed that RS2Z35 and RS2Z36 are important players in the stress response and thermotolerance in plants that mitigate the negative effects of HS on RNA splicing homeostasis.

plant biology↗

bioRxiv2023

NYUS.2: an Automated Machine Learning Prediction Model for the Large-scale Real-time Simulation of Grapevine Freezing Tolerance in North America

O_LIAccurate and real-time monitoring of grapevine freezing tolerance is crucial for the sustainability of the grape industry in cool climate viticultural regions. However, on-site data is limited. Current prediction models underperform under diverse climate conditions, which limits the large-scale deployment of these methods. C_LIO_LIWe combined grapevine freezing tolerance data from multiple regions in North America and generated a predictive model based on hourly temperature-derived features and cultivar features using AutoGluon, an automatic machine learning engine. Feature importance was quantified by AutoGluon and SHAP value. The final model was evaluated and compared with previous models for its performance under different climate conditions. C_LIO_LIThe final model achieved an overall 1.36 {degrees}C root-mean-square error during model testing and outperformed two previous models using three test cultivars at all testing regions. Two feature importance quantification methods identified five shared essential features. Detailed analysis of the features indicates that the model might have adequately extracted some biological mechanisms during training. C_LIO_LIThe final model, named NYUS.2, was deployed along with two previous models as an R shiny-based application in the 2022-2023 dormancy season, enabling large-scale and real-time simulation of grapevine freezing tolerance in North America for the first time. C_LI

plant biology↗

bioRxiv2023

hGRAD - a versatile 'one-fits-all' system for the acute depletion of RNA binding proteins in nuclear condensates

Nuclear RNA binding proteins (RBPs) are difficult to study because they often belong to large protein families and form extensive networks of auto- and cross- regulation. They are highly abundant and often localize to condensates with a slow turnover, requiring long depletion times or knockouts that cannot distinguish between direct and indirect or compensatory effects. Here, we developed a system that is optimized for the rapid degradation of nuclear RBPs, called hGRAD. It comes as a 'one-fits-all' plasmid, and integration into any cell line that expresses endogenously GFP-tagged proteins allows an inducible, rapid and complete knockdown. We show that the nuclear RBPs SRSF3, SRSF5, SRRM2 and NONO are completely cleared from nuclear speckles and paraspeckles within two hours. hGRAD works in various cell types, is more efficient than other methods and does not require the expression of exogenous ubiquitin ligases. Combining SRSF5 hGRAD degradation with Nascent-seq uncovered highly dynamic transient transcript changes, compensatory mechanisms and that SRSF5 promotes transcript stability.

cell biology↗

bioRxiv2023

A Refined Phylochronology of the Second Plague Pandemic in Western Eurasia

Although dozens of ancient Yersinia pestis genomes and a vast corpus of documentary data are available, the origin and spread of consecutive outbreaks of the Second Plague Pandemic in Europe (14th-18th c.) are still poorly understood. For the majority of ancient genomes, only radiocarbon dates spanning several decades are available, hampering an association with historically recorded plague outbreaks. Here, we present new genomic evidence of the Second Pandemic from 11 sites in England, Estonia, the Netherlands, Russia, and Switzerland yielding 11 Y. pestis genomes with >4-fold mean coverage dating to between 1349 and 1710. In addition, we present a novel approach for integrating the chronological information retrieved from phylogenetic analysis with their respective radiocarbon dates, based on a novel methodology offering more precise dating intervals. Together with a fine-grained analysis of documentarily recorded plague outbreaks, this allows us to tentatively associate all available Y. pestis genomes of the Second Pandemic with historically documented plague outbreaks. Through these combined multidisciplinary analytical efforts, our newly sequenced genomes can be attributed to the Black Death in Cambridge (England), the pestis tertia or pestis quarta in the late 14th century (Estonia), previously unknown branches emerging in the 15th century (Estonia, the Netherlands and England), and a widespread pandemic in Eastern Europe around 1500 (western Russia), which all seem to have originated from one or multiple reservoirs located in Central Europe. While the latter continued to harbour a major Y. pestis lineage at least until the 1630s, represented by new genomes of the Thirty Years War plague (Switzerland), another lineage consecutively spread into Europe between the 17th and 18th century from the Ottoman Empire, as evidenced by a genome associated with the Great Northern War plague (Estonia). By combining phylogenetic analysis with a systematic historical reconstruction based on textual sources and an innovative phylogenetically informed radiocarbon modelling (PhIRM), we offer a new groundbreaking interdisciplinary approach that solves several fundamental methodological challenges associated with phylogenetic and spatio-temporal reconstruction of historical pandemics.

genomics↗

bioRxiv2023

The chromatin landscape of healthy and injured cell types in the human kidney

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. However, comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measured dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We established a comprehensive and spatially-anchored epigenomic atlas to define the kidneys active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we noted distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulated the transition between health and injury, while in thick ascending limb cells this transition was regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguished two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

molecular biology↗

bioRxiv2022

Enterotypes of the human gut mycobiome

The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. Here, we identify and characterize four mycobiome enterotypes using ITS profiling of 3,363 samples from 16 cohorts across three continents, including 572 newly profiled samples from China. These enterotypes exhibit stability across populations and geographical locations and significant correlation with bacterial enterotypes. Particularly, we notice that fungal enterotypes have a strong age preference, where the enterotype dominated by Candida (i.e., fun_C_E enterotype) is enriched in the elderly population and confers an increased risk of multiple diseases associated with compromised intestinal barrier. In addition, bidirectional mediation analysis reveals that the fungi-contributed aerobic respiration pathway associated with fun_C_E enterotype might mediate the association between the compromised intestinal barrier and aging. TeaserAs an integral part of the human gut microbiome, the fungi, which co-habit with prokaryotic microbiome in the gut, play important role in the intestinal ecology and human health. Yet, the overall structure of the human gut mycobiome and the inter-individual variation worldwide remain largely unclear. Lai et al. analyzed the fungal profiles of 3,363 samples from 16 cohorts across three continents, and identified four fungal enterotypes that exhibit stability across populations. They found that fungal enterotypes showed age preference, where a Candida dominated enterotype was enriched in the elderly population and confers an increased risk of multiple diseases and more severe compromised intestinal barrier. Furthermore, they determined one fungi-contributed aerobic respiration pathway could mediate the association between the compromised intestinal barrier and aging.

bioinformatics↗

bioRxiv2022

An advanced sequence clustering and designation workflow reveals the enzootic maintenance of a dominant West Nile virus subclade in Germany

West Nile virus (WNV) is the most widespread arthropod-borne (arbo) virus and the primary cause of arboviral encephalitis globally. Members of WNV species genetically diverged and are classified into different hierarchical groups below species rank. However, the demarcation criteria for allocating WNV sequences into these groups remain individual, inconsistent, and the use of names for different levels of the hierarchical levels is unstructured. In order to have an objective and comprehensible grouping of WNV sequences, we developed an advanced grouping workflow using the "affinity propagation clustering"-algorithm and newly included the "agglomerative hierarchical clustering"-algorithm for the allocation of WNV sequences into different groups below species rank. In addition, we propose to use a fixed set of terms for the hierarchical naming of WNV below species level and a clear decimal numbering system to label the determined groups. For validation, we applied the refined workflow to WNV sequences that have been previously grouped into various lineages, clades, and clusters in other studies. Although our workflow regrouped some WNV sequences, overall, it generally corresponds with previous groupings. We employed our novel approach to the sequences from the WNV circulation in Germany 2020, primarily from WNV-infected birds and horses. Besides two newly defined minor (sub)clusters comprising only of three sequences each, subcluster 2.5.3.4.3c was the predominant WNV sequence group detected in Germany from 2018-20. This predominant subcluster was also associated with at least five human WNV-infections in 2019-20. In summary, our analyses imply that the genetic diversity of the WNV population in Germany is shaped by enzootic maintenance of the dominant WNV subcluster accompanied by sporadic incursions of other rare clusters and subclusters. Moreover, we show that our refined approach for sequence grouping yields meaningful results. Although we primarily aimed at a more detailed WNV classification, the presented workflow can also be applied to the objective genotyping of other virus species.

genetics↗

bioRxiv2022

Tracking canopy gap dynamics across four sites in the Brazilian Amazon

Background information to give context to the studyCanopy gaps are the most evident manifestation of how disturbances disrupt forest landscapes. The size distribution and return frequency of gaps, and subsequent recovery processes, determine whether the old-growth state can be reached. The aim or research questionWe used remote sensing metrics to compare the disturbance regime of four Amazon regions based on the size distribution of gaps, their dynamics and geometric characteristics. A brief summary of the methodology usedWe assessed gap dynamics at four sites in the central, central eastern, southeastern, and northeastern regions of the Brazilian Amazon using repeated airborne laser scanning surveys. We developed a novel analysis to quantify four possible stages of gap dynamics: formation, expansion, persisting and recovering. For that, we overlapped layers of gap locations from two consecutive airborne laser scanning surveys. Key results with some significance measuresThe gap fraction in our study sites varied between 1.26% to 7.84%. All the sites have similar proportion of gaps among size classes. What notably changed between sites was not the gap size-distribution, but the relative importance of stages of gap dynamics. Growing and persisting rates were greatest in the site with the stronger seasonal variation in climate, lower annual precipitation, higher mean wind speed and higher solar radiation. The conclusions, which address the main aimsThe concept of stability reflects the tendency of a system to quickly return to a position of equilibrium when disturbed. We showed that gap dynamics varied among sites, with one example of low recovery rate contrasted to three other sites with faster recovery. Our results support that such as assessing the size distribution of gaps, investigating their return frequency and severity is crucial for understanding forest dynamics at the landscape and regional scales.

ecology↗

bioRxiv2022

Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic

Golden Syrian hamsters (Mesocricetus auratus) are used as a research model for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Millions of Golden Syrian hamsters are also kept as pets in close contact to humans. To determine the minimum infective dose (MID) for assessing the zoonotic transmission risk, and to define the optimal infection dose for experimental studies, we orotracheally inoculated hamsters with SARS-CoV-2 doses from 1*105 to 1*10-4 tissue culture infectious dose 50 (TCID50). Body weight and virus shedding were monitored daily. 1*10-3 TCID50 was defined as the MID, and this was still sufficient to induce virus shedding at levels up to 102.75 TCID50/ml, equaling the estimated MID for humans. Virological and histological data revealed 1*102 TCID50 as the optimal dose for experimental infections. This compellingly high susceptibility resulting in productive infections in Golden Syrian hamsters needs to be considered also as a source of SARS-CoV-2 infections in humans.

microbiology↗

bioRxiv2022

A protocol for locating and counting transgenic sequences from laboratory animals using a map-then-capture (MapCap) sequencing workflow: procedure and application of results.

Transgenic rodent models for human diseases have been widely used over the past 50 years and are a mainstay of many biomedical research programs. Oftentimes the sequence of the transgenic segment of DNA is carefully designed but incorporation of this DNA into the host genome is less well understood. Structural variation and insertional mutagenesis may occur at transgenic insertion sites. Here, we present a robust workflow including identification of the transgene locus via selective Illumina sequencing followed by Cas9-mediated target DNA enrichment of the locus, which successfully identified beginning and end sites of a large transgenic insertion into a murine model for human amylin-induced type II diabetes. Enriched sequences were mapped via Oxford Nanopore sequencing. Although the insertion was too long for a single mapped genetic sequence to encompass, the method provided multiple insights relevant to the animal model: a minimum number of forward- and reverse-facing transcript copies as well as characterization of an inversion point within the insertion site. The insertion start point containing both murine and human DNA was used to identify and separate animals hemizygous for the transgenic insertion from homozygous animals. This identification could be performed early in the rodent life cycle prior to maturation (i.e. breeding age), thus allowing for management of colony phenotypes and eliminating the need to "genotype by phenotype" later on (onset of amylin-induced type II diabetes does not occur until ~8-10 weeks of age for this model). We further confirmed our homozygous diabetic mice function the same as colonies established in other labs and present full antibody and fluorescent-staining protocols (available in SI). Lastly, we note that, due to our genotyping, a novel animal was identified within our colony: non-diabetic homozygous mice. Indeed, only 37% of homozygous mice bred in our colony became diabetic. AUTHOR SUMMARY (for broad audience)Transgenic rodent models are important to studying human diseases. When creating a new rodent model, one may insert new DNA into a well-characterized background genome. However, it is oftentimes not known where the new DNA was incorporated, how many times it was incorporated, or if any coding sequences or regulatory elements within native DNA were disrupted. Here, we have developed a method to characterize transgenic animals, and have applied it to a popular model for studying human amylin-induced type II diabetes.

genetics↗

bioRxiv2021

Live-cell microscopy or fluorescence anisotropy with budded baculoviruses - which way to go with measuring ligand binding to M4 muscarinic receptors?

M4 muscarinic receptor is a G protein-coupled receptor that has been associated with alcohol and cocaine abuse, Alzheimers disease and schizophrenia which makes it an interesting drug target. For many G protein-coupled receptors, the development of high-affinity fluorescence ligands has expanded the options for high throughput screening of drug candidates and serve as useful tools in fundamental receptor research. So far, the lack of suitable fluorescence ligands has limited studying M4 receptor ligand binding. Here, we explored the possibilities of using fluorescence-based methods for studying binding affinity and kinetics to M4 receptor of both labeled and unlabeled ligands. We used two TAMRA-labeled fluorescence ligands, UR-MK342 and UR-CG072, for assay development. Using budded baculovirus particles as M4 receptor preparation and fluorescence anisotropy method, we determined the affinities and binding kinetics of both fluorescence ligands. The fluorescence ligands could also be used as reported probes for determining binding affinities of a set of unlabeled ligands. Based on these results, we took a step further towards a more natural signaling system and developed a method using live CHO-K1-hM4R cells and automated fluorescence microscopy suitable for routine determination of unlabeled ligand affinities. For quantitative image analysis, we developed random forest and deep learning-based pipelines for cell segmentation. The pipelines were integrated into the user-friendly open-source Aparecium software. Both developed methods were suitable for measuring fluorescence ligand saturation binding, association and dissociation kinetics as well as for screening binding affinities of unlabeled ligands. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/473643v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@17dfac6org.highwire.dtl.DTLVardef@1db1760org.highwire.dtl.DTLVardef@dba2a0org.highwire.dtl.DTLVardef@191f149_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2021

Tracking the rates and mechanisms of canopy damage and recovery following Hurricane Maria using multitemporal lidar data

Hurricane Maria (Category 4) snapped and uprooted canopy trees, removed large branches, and defoliated vegetation across Puerto Rico. The magnitude of forest damages and the rates and mechanisms of forest recovery following Maria provide important benchmarks for understanding the ecology of extreme events. We used airborne lidar data acquired before (2017) and after Maria (2018, 2020) to quantify landscape-scale changes in forest structure along a 439-ha elevational gradient (100 to 800 m) in the Luquillo Experimental Forest. Damages from Maria were widespread, with 73% of the study area losing [≥]1 m in canopy height (mean = -7.1 m). Taller forests at lower elevations suffered more damage than shorter forests above 600 m. Yet only 13% of the study area had canopy heights [≤]2 m in 2018, a typical threshold for forest gaps, highlighting the importance of damaged trees and advanced regeneration on post-storm forest structure. Heterogeneous patterns of regrowth and recruitment yielded shorter and more open forests by 2020. Nearly 45% of forests experienced initial height loss (<-1 m, 2017-2018) followed by rapid height gain (>1 m, 2018-2020), whereas 21.6% of forests with initial height losses showed little or no height gain, and 17.8% of forests exhibited no structural changes >|1| m in either period. Canopy layers <10 m accounted for most increases in canopy height and fractional cover between 2018-2020, with gains split evenly between height growth and lateral crown expansion by surviving individuals. These findings benchmark rates of gap formation, crown expansion, and canopy closure following hurricane damage. MANUSCRIPT HIGHLIGHTSO_LIHurricane Maria gave forests a haircut by toppling trees and shearing branches. C_LIO_LIRegrowth after Maria was patchy, with equal areas of height gain and no change. C_LIO_LI3-D measures of forest recovery after hurricanes can improve ecosystem models. C_LI

ecology↗

bioRxiv2020

Human mobility at Tell Atchana (Alalakh) during the 2nd millennium BC: integration of isotopic and genomic evidence

The Middle and Late Bronze Age Near East, a period roughly spanning the second millennium BC (ca. 2000-1200 BC), is frequently referred to as the first international age, characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated at Tell Atchana (Alalakh), situated in the northern Levant, we explore the role of mobility at the capital of a regional kingdom. We generated strontium isotope data for 53 individuals, oxygen isotope data for 77 individuals, and added ancient DNA data from 9 new individuals to a recently published dataset of 28 individuals. A dataset like this, from a single site in the Near East, is thus far unparalleled in terms of both its breadth and depth, providing the opportunity to simultaneously obtain an in-depth view of individual mobility and also broader demographic insights into the resident population. The DNA data reveals a very homogeneous gene pool, with only one outlier. This picture of an overwhelmingly local ancestry is consistent with the evidence of local upbringing in most of the individuals indicated by the isotopic data, where only five were found to be non-local. High levels of contact, trade, and exchange of ideas and goods in the Middle and Late Bronze Ages, therefore, seem not to have translated into high levels of individual mobility detectable at Tell Atchana.

genetics↗

bioRxiv2020

Interacting effects of frontal lobe neuroanatomy and working memory capacity to older listeners' speech recognition in noise

Many older adults are struggling with understanding spoken language, particularly when background noise interferes with comprehension. In the present study, we investigated a potential interaction between two well-known factors associated with greater speech-in-noise (SiN) reception thresholds in older adults, namely a) lower working memory capacity and b) age-related structural decline of frontal lobe regions. In a sample of older adults (N=25) and younger controls (N=13) with normal pure-tone thresholds, SiN reception thresholds and working memory capacity were assessed. Furthermore, T1-weighted structural MR-images were recorded to analyze neuroanatomical traits (i.e., cortical thickness (CT) and cortical surface area (CSA)) of the cortex. As expected, the older group showed greater SiN reception thresholds compared to the younger group. We also found consistent age-related atrophy (i.e., lower CT) in brain regions associated with SiN recognition namely the superior temporal lobe bilaterally, the right inferior frontal and precentral gyrus, as well as the left superior frontal gyrus. Those older participants with greater atrophy in these brain regions also showed greater SiN reception thresholds. Interestingly, the association between CT in the left superior frontal gyrus and SiN reception thresholds was moderated by individual working memory capacity. Older adults with greater working memory capacity benefitted more strongly from thicker frontal lobe regions when it comes to improve SiN recognition. Overall, our results fit well into the literature showing that age-related structural decline in auditory- and cognition-related brain areas is associated with greater SiN reception thresholds in older adults. However, we highlight that this association changes as a function of individual working memory capacity. We therefore believe that future interventions to improve SiN recognition in older adults should take into account the role of the frontal lobe as well as individual working memory capacity. HighlightsO_LISpeech-in-noise (SiN) reception thresholds are significantly increased with higher age, independently of pure-tone hearing loss C_LIO_LIGreater SiN reception thresholds are associated with cortical thinning in several auditory-, linguistic-, and cognitive-related brain areas, irrespective of pure-tone hearing loss C_LIO_LIGreater cortical thinning in the left superior frontal lobe is detrimental for SiN recognition in older, but not younger adults C_LIO_LIOlder adults with greater working memory capacity benefit more strongly from structural integrity of left superior frontal lobe for SiN recognition C_LI

neuroscience↗