Dental-anthropologische Untersuchungen an mittelalterlichen und frühneuzeitlichen Populationen aus Weimar unter besonderer Berücksichtigung von Schmelzstrukturstörungen

Dental-anthropologische Untersuchungen können zu Erkenntnissen über orale Erkrankungsmuster, Ernährungseinflüsse und Veränderungen der Lebens¬bedingungen unserer Vorfahren beitragen. Ziel der vorliegenden Untersuchung war die Analyse dentaler Erkrankungen einer mittelalterlichen und einer frühneuzeitlichen Population aus Weimar, Thüringen

Closure times of neurocranial sutures and synchondroses in Persian compared to Domestic Shorthair cats

Human-directed selective breeding has modified the phenotype of the modern Persian cat towards an extreme brachycephalic phenotype (‘peke-face’ Persian), which originates from a spontaneous mutation that first appeared in the 1950s in traditional Persian types. It was suggested that the peke-face phenotype results from pathologic skull development and might represent a craniosynostosis of the coronal sutures. We followed this hypothesis and investigated the time dependent status of the neurocranial sutures and synchondroses in an ontogenetic series of doll-faced and peke-faced Persian cats compared to Domestic Shorthair cats (DSHs). Cranial suture closure was assessed by examining an ontogenetic series of formalin-fixed head specimens (n = 55) and dry skulls (n = 32) using micro-computed tomography. Sagittal, metopic, coronal and lambdoid sutures as well as intersphenoidal, spheno-occipital and spheno-ethmoid synchondroses were examined. Logistic regression analysis was performed to test the global effect of age on suture closure within a group of peke-face Persians, doll-face Persians and DSHs and the 50% probability of having a closed suture was calculated and compared between groups. Age was a perfect predictor for the condition of the coronal sutures in peke-face Persians. Coronal sutures were found to be closed at 0–0.3 months. In doll-face and DSHs, coronal sutures were open throughout the lifetime with the exception of a few very old cats. Results of this study confirmed a coronal craniosynostosis that likely causes the extreme brachycephalic skull morphology in the peke-face Persian

Machine Learning Reveals Time-Varying Microbial Predictors with Complex Effects on Glucose Regulation

The incidence of type 2 diabetes (T2D) has been increasing globally, and a growing body of evidence links type 2 diabetes with altered microbiota composition. Type 2 diabetes is preceded by a long prediabetic state characterized by changes in various metabolic parameters. We tested whether the gut microbiome could have predictive potential for T2D development during the healthy and prediabetic disease stages. We used prospective data of 608 well-phenotyped Finnish men collected from the population-based Metabolic Syndrome in Men (METSIM) study to build machine learning models for predicting continuous glucose and insulin measures in a shorter (1.5 year) and longer (4 year) period. Our results show that the inclusion of the gut microbiome improves prediction accuracy for modeling T2D-associated parameters such as glycosylated hemoglobin and insulin measures. We identified novel microbial biomarkers and described their effects on the predictions using interpretable machine learning techniques, which revealed complex linear and nonlinear associations. Additionally, the modeling strategy carried out allowed us to compare the stability of model performance and biomarker selection, also revealing differences in short-term and long-term predictions. The identified microbiome biomarkers provide a predictive measure for various metabolic traits related to T2D, thus providing an additional parameter for personal risk assessment. Our work also highlights the need for robust modeling strategies and the value of interpretable machine learning.IMPORTANCE Recent studies have shown a clear link between gut microbiota and type 2 diabetes. However, current results are based on cross-sectional studies that aim to determine the microbial dysbiosis when the disease is already prevalent. In order to consider the microbiome as a factor in disease risk assessment, prospective studies are needed. Our study is the first study that assesses the gut microbiome as a predictive measure for several type 2 diabetes-associated parameters in a longitudinal study setting. Our results revealed a number of novel microbial biomarkers that can improve the prediction accuracy for continuous insulin measures and glycosylated hemoglobin levels. These results make the prospect of using the microbiome in personalized medicine promising

Quantitative Proteomics and Differential Protein Abundance Analysis after Depletion of Putative mRNA Receptors in the ER Membrane of Human Cells Identifies Novel Aspects of mRNA Targeting to the ER

In human cells, one-third of all polypeptides enter the secretory pathway at the endoplasmic reticulum (ER). The specificity and efficiency of this process are guaranteed by targeting of mRNAs and/or polypeptides to the ER membrane. Cytosolic SRP and its receptor in the ER membrane facilitate the cotranslational targeting of most ribosome-nascent precursor polypeptide chain (RNC) complexes together with the respective mRNAs to the Sec61 complex in the ER membrane. Alternatively, fully synthesized precursor polypeptides are targeted to the ER membrane post-translationally by either the TRC, SND, or PEX19/3 pathway. Furthermore, there is targeting of mRNAs to the ER membrane, which does not involve SRP but involves mRNA- or RNC-binding proteins on the ER surface, such as RRBP1 or KTN1. Traditionally, the targeting reactions were studied in cell-free or cellular assays, which focus on a single precursor polypeptide and allow the conclusion of whether a certain precursor can use a certain pathway. Recently, cellular approaches such as proximity-based ribosome profiling or quantitative proteomics were employed to address the question of which precursors use certain pathways under physiological conditions. Here, we combined siRNA-mediated depletion of putative mRNA receptors in HeLa cells with label-free quantitative proteomics and differential protein abundance analysis to characterize RRBP1- or KTN1- involving precursors and to identify possible genetic interactions between the various targeting pathways. Furthermore, we discuss the possible implications on the so-called TIGER domains and critically discuss the pros and cons of this experimental approach

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals

Prevalence of Stunting and Relationship between Stunting and Associated Risk Factors with Academic Achievement and Cognitive Function: A Cross-Sectional Study with South African Primary School Children

Childhood stunting can have negative long-term consequences on cognitive development, academic achievement, and economic productivity later in life. We determined the prevalence of stunting and examined whether stunting and associated risk factors (low dietary diversity, insufficient hemoglobin, food insecurity, and soil-transmitted helminth (STH) infections) are associated with academic achievement and cognitive function among South African children living in marginalized communities. A cross-sectional sample of 1277 children (aged 5-12 years) was analyzed. Stunting was defined according to 2007 WHO growth references. Cognitive functioning was measured with the computerized Flanker task and academic performance via school grades. Blood and stool samples were collected to obtain hemoglobin level and STH infection. Dietary diversity was assessed by a food frequency questionnaire. Associations were examined via mixed linear regression (with school class as a random intercept). Nine percent of the children were stunted (95% CI: 7.6-10.8%). Low dietary diversity (β = 0.13,; p; = 0.004), food insecurity (β = -0.12,; p; = 0.034), and stunting (β = -0.13,; p; = 0.031) were associated with poorer end of the year results among girls. No such associations were found among boys. No significant associations were found for socioeconomic status and hemoglobin levels. The prevalence of stunting and STH infections were low in the present sample. Risk factors seem differently associated with girls' and boys' academic achievement. Promoting nutrition may help to promote academic achievement among girls living in low- and middle-income countries

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals

Associations of growth impairment and body composition among South African school-aged children enrolled in the KaziAfya project

(1) Background: Early childhood malnutrition may result in increased fat mass (FM) among school-aged children in low- and middle-income countries (LMICs). We explored whether South African children with shorter stature have greater overall and abdominal FM compared to normal stature children. (2) Methods: Baseline assessments of body composition and weight were determined among school-aged children enrolled in a randomized controlled trial in Port Elizabeth, South Africa, using bioelectrical impedance analysis. Multiple linear regression models tested associations of children's height and degree of stunting with FM, fat free mass (FFM), truncal fat mass (TrFM), and truncal fat free mass (TrFFM) overall and by sex. (3) Results: A total of 1287 children (619 girls, 668 boys) were assessed at baseline. Reduced child height was associated with higher FM and lower FFM and TrFFM, but these associations were reversed with increases in height. Girls classified as mildly or moderately/severely stunted had higher FM and TrFM but lower FFM and TrFFM, while no association was found for boys. (4) Conclusions: Our study suggests that efforts to reduce the non-communicable disease burden in LMICs should target growth-impaired children who may have greater overall FM and greater abdominal FM

Evaluation of a Physical Activity and Multi-Micronutrient Intervention on Cognitive and Academic Performance in South African Primary Schoolchildren

Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1 completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group x time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance

Identification of signal peptide features for substrate specificity in human Sec62/Sec63-dependent ER protein import

In mammalian cells, one‐third of all polypeptides are integrated into the membrane or translocated into the lumen of the endoplasmic reticulum (ER) via the Sec61 channel. While the Sec61 complex facilitates ER import of most precursor polypeptides, the Sec61‐associated Sec62/Sec63 complex supports ER import in a substrate‐specific manner. So far, mainly posttranslationally imported precursors and the two cotranslationally imported precursors of ERj3 and prion protein were found to depend on the Sec62/Sec63 complex in vitro. Therefore, we determined the rules for engagement of Sec62/Sec63 in ER import in intact human cells using a recently established unbiased proteomics approach. In addition to confirming ERj3, we identified 22 novel Sec62/Sec63 substrates under these in vivo‐like conditions. As a common feature, those previously unknown substrates share signal peptides (SP) with comparatively longer but less hydrophobic hydrophobic region of SP and lower carboxy‐terminal region of SP (C‐region) polarity. Further analyses with four substrates, and ERj3 in particular, revealed the combination of a slowly gating SP and a downstream translocation‐disruptive positively charged cluster of amino acid residues as decisive for the Sec62/Sec63 requirement. In the case of ERj3, these features were found to be responsible for an additional immunoglobulin heavy‐chain binding protein (BiP) requirement and to correlate with sensitivity toward the Sec61‐channel inhibitor CAM741. Thus, the human Sec62/Sec63 complex may support Sec61‐channel opening for precursor polypeptides with slowly gating SPs by direct interaction with the cytosolic amino‐terminal peptide of Sec61α or via recruitment of BiP and its interaction with the ER‐lumenal loop 7 of Sec61α. These novel insights into the mechanism of human ER protein import contribute to our understanding of the etiology of SEC63‐linked polycystic liver disease