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The main sponge cake ingredients are flour, sucrose, eggs and leavening agents. Exogenous lipids (e.g., monoacylglycerols) are often used to increase air–liquid interface stability in the batter. There is a consumer trend to avoid foods containing such additives. We here reasoned that egg yolk may be an alternative source of surface-active lipids and set out to study the role of egg yolk lipids during sponge cake making. This was done by relocating or removing them prior to batter preparation using ethanol treatments and examining how this affects cake (batter) properties and structure setting during baking. Most egg yolk lipids occur within spherical low-density lipoproteins (LDLs) which were disintegrated by the ethanol treatments. Results showed that egg yolk lipids impact air–liquid interface stability and less so cake structure setting. To prepare high-quality sponge cakes by multistage mixing preferably intact LDLs or, alternatively, their components are needed to incorporate sufficient air during mixing and to stabilize it after mixing. It was also shown that the batter contains intact LDLs in the continuous phase and disintegrated LDLs at air–liquid interfaces. Sponge cake contains intact LDLs in the cake matrix, disintegrated LDLs at air–crumb interfaces and disintegrated LDLs incorporated into the protein network.

Protein degradation is a fundamental process in all living organisms. An important part of this system is a multisubunit, barrel-shaped protease complex called the proteasome. This enzyme is directly responsible for the proteolysis of ubiquitin- or pup-tagged proteins to smaller peptides. In this study, we present a series of 92 psoralen derivatives, of which 15 displayed inhibitory potency against the Mycobacterium tuberculosis proteasome in low micromolar concentrations. The best inhibitors, i.e., 8, 11, 13 and 15, exhibited a mixed type of inhibition and overall good inhibitory potency in biochemical assays. N-(cyanomethyl)acetamide 8 (Ki = 5.6 µM) and carboxaldehyde-based derivative 15 (Ki = 14.9 µM) were shown to be reversible inhibitors of the enzyme. On the other hand, pyrrolidine-2,5-dione esters 11 and 13 irreversibly inhibited the enzyme with Ki values of 4.2 µM and 1.1 µM, respectively. In addition, we showed that an established immunoproteasome inhibitor, PR-957, is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 ± 1.9 µM, kinact/Ki = 96 ± 41 M−1·s−1). These compounds represent interesting hit compounds for further optimization in the development of new drugs for the treatment of tuberculosis.

Organic fertilizers have been shown to stimulate CH4 uptake from agricultural soils. Managing fertilizer application to maximize this effect and to minimize emission of other greenhouse gasses offers possibilities to increase sustainability of agriculture. To tackle this challenge, we incubated an agricultural soil with different organic amendments (compost, sewage sludge, digestate, cover crop residues mixture), either as single application or in a mixture and subjected it to different soil moisture concentrations using different amounts of organic amendments. GHG fluxes and in vitro CH4 oxidation rates were measured repeatedly, while changes in organic matter and abundance of GHG relevant microbial groups (nitrifiers, denitrifiers, methanotrophs, methanogens) were measured at the end of the incubation. Overall the dynamics of the analyzed GHGs differed significantly. While CO2 and N2O differed considerably between the treatments, CH4 fluxes remained stable. In contrast, in vitro CH4 oxidation showed a clear increase for all amendments over time. CO2 fluxes were mostly dependent on the amount of organic residue that was used, while N2O fluxes were affected more by soil moisture. Several combinations of amendments led to reductions of CO2, CH4, and/or N2O emissions compared to un-amended soil. Most optimal GHG balance was obtained by compost amendments, which resulted in a similar overall GHG balance as compared to the un-amended soil. However, compost is not very nutrient rich potentially leading to lower crop yield when applied as single fertilizer. Hence, the combination of compost with one of the more nutrient rich organic amendments (sewage sludge, digestate) provides a trade-off between maintaining crop yield and minimizing GHG emissions. Additionally, we could observe a strong increase in microbial communities involved in GHG consumption in all amendments, with the strongest increase associated with cover crop residue mixtures. Future research should focus on the interrelation of plants, soil, and microbes and their impact on the global warming potential in relation to applied organic amendments.

Objectives To assess access to adequate water, sanitation and hygiene (WASH) among people with disabilities at the household and individual level.Design Cross-sectional surveys.Setting Data were included from five district-level or regional-level surveys: two in Bangladesh (Bangladesh-1, Bangladesh-2), and one each in Cameroon, Malawi and India.Participants 99 252 participants were sampled across the datasets (range: 3567–75 767), including 2494 with disabilities (93–1374).Outcome Prevalence of access to WASH at household and individual level.Data analysis Age/sex disaggregated disability prevalence estimates were calculated accounting for survey design. The Unicef/WHO Joint Monitoring Programme definitions were used to classify facilities as improved/unimproved. Multivariable logistic regression was undertaken to compare between households with/without a person with a disability, and to identify predictors of access among people with disabilities.Results There were no differences in access to improved sanitation or water sources between households with/without members with disabilities across the datasets. In Bangladesh-2, households including a person with a disability were more likely to share facilities with other households (OR 1.3, 95% CI 1.1 to 1.5). Households with people with disabilities were more likely to spend >30 min (round-trip) collecting drinking water than households without in both Cameroon (OR 1.8, 95% CI 1.0 to 3.4) and India (OR 2.3, 95% CI 1.2 to 4.7). Within households, people with disabilities reported difficulties collecting water themselves (23%–80% unable to) and accessing the same sanitation facilities as other household members, particularly without coming into contact with faeces (up to 47% in Bangladesh-2). These difficulties were most marked for people with more severe impairments.Conclusions People with disabilities may not have poorer access to WASH at the household level, but may have poorer quality of access within their households. Further programmatic work is needed to ensure WASH facilities are inclusive of people with disabilities.

Continuously rising atmospheric CO2 concentrations may lead to an increased transfer of organic C from plants to the soil through rhizodeposition and may affect the interaction between the C- and N-cycle. For instance, fumigation of soils with elevated CO2 (eCO2) concentrations (20% higher compared to current atmospheric concentrations) at the Giessen Free-Air Carbon Dioxide Enrichment (GiFACE) sites resulted in a more than 2-fold increase of long-term N2O emissions and an increase in dissimilatory reduction of nitrate compared to ambient CO2 (aCO2). We hypothesized that the observed differences in soil functioning were based on differences in the abundance and composition of microbial communities in general and especially of those which are responsible for N-transformations in soil. We also expected eCO2 effects on soil parameters, such as on nitrate as previously reported. To explore the impact of long-term eCO2 on soil microbial communities, we applied a molecular approach (qPCR, T-RFLP, and 454 pyrosequencing). Microbial groups were analyzed in soil of three sets of two FACE plots (three replicate samples from each plot), which were fumigated with eCO2 and aCO2, respectively. N-fixers, denitrifiers, archaeal and bacterial ammonia oxidizers, and dissimilatory nitrate reducers producing ammonia were targeted by analysis of functional marker genes, and the overall archaeal community by 16S rRNA genes. Remarkably, soil parameters as well as the abundance and composition of microbial communities in the top soil under eCO2 differed only slightly from soil under aCO2. Wherever differences in microbial community abundance and composition were detected, they were not linked to CO2 level but rather determined by differences in soil parameters (e.g., soil moisture content) due to the localization of the GiFACE sets in the experimental field. We concluded that +20% eCO2 had little to no effect on the overall microbial community involved in N-cycling in the soil but that spatial heterogeneity over extended periods had shaped microbial communities at particular sites in the field. Hence, microbial community composition and abundance alone cannot explain the functional differences leading to higher N2O emissions under eCO2 and future studies should aim at exploring the active members of the soil microbial community.

Advanced Trauma Life Support (ATLS) programs are recognized as the standard educational trauma program worldwide. Data suggest that ATLS has a positive impact on the value of trauma care. The ATLS Hungary program has been started in 2005, celebrating its 10-year anniversary this year. In the present brief communication a brief overview is provided on the program.Student evaluation and statistical data about the participants were collected throughout the 10-year history of the Hungarian program.Student evaluation shows a high level of satisfaction amongst the participating doctors. Most participants are working in higher level centers. The Hungarian program shows good quality according to the participants. Establishing at least one new center is crucial to be able to provide the course for every professional interested in it or required to take it.

Brown rats (Rattus norvegicus) have been identified as potential carriers of Yersinia enterocolitica and Y. pseudotuberculosis, the etiological agents of yersiniosis, the third most reported bacterial zoonosis in Europe. Enteropathogenic Yersinia spp. are most often isolated from rats during yersiniosis cases in animals and humans, and from rats inhabiting farms and slaughterhouses. Information is however lacking regarding the extent to which rats act as carriers of these Yersinia spp.. In 2013, 1088 brown rats across Flanders, Belgium, were tested for the presence of Yersinia species by isolation method. Identification was performed using MALDI-TOF MS, PCR on chromosomal- and plasmid-borne virulence genes, biotyping and serotyping. Yersinia spp. were isolated from 38.4% of the rats. Of these, 53.4% were designated Y. enterocolitica, 0.7% Y. pseudotuberculosis and 49.0% other Yersinia species. Two Y. enterocolitica possessing the virF-, ail- and ystA-gene were isolated. Additionally, the ystB-gene was identified in 94.1% of the other Y. enterocolitica isolates, suggestive for biotype 1A. Three of these latter isolates simultaneously possessed the ail-virulence gene. Significantly more Y. enterocolitica were isolated during winter and spring compared to summer. Based on our findings we can conclude that brown rats are frequent carriers for various Yersinia spp., including Y. pseudotuberculosis and (human pathogenic) Y. enterocolitica which are more often isolated during winter and spring.

PURPOSE: To investigate epilepsy-induced changes in effective connectivity between the non-epileptic amygdalo-hippocampal complex (AHC) and the rest of the brain in patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). METHODS: Thirty-three patients with unilateral MTLE associated with HS (20 females, mean age: 36 years, 19 left HS) and 33 adult controls matched for age and gender underwent (18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Right-HS patients' FDG-PET data were flipped to obtain a left-epileptic-focus-lateralized group of patients. Voxels of interest (VOI) were selected within the cytoarchitectonic probabilistic maps of the non-epileptic AHC (probability level = 100%, SPM8 Anatomy toolbox v1.7). Patients and controls were compared using VOI metabolic activity as covariate of interest to search for epilepsy-induced changes in the contribution of the non-epileptic AHC to the level of metabolic activity in other brain areas. Age, gender, duration of epilepsy, seizure type and frequency were used as covariates of no-interest for connectivity analyses. KEY FINDINGS: Significant decrease in effective connectivity was found between the non-epileptic AHC and ventral prefrontal cortical areas bilaterally, as well as with the temporal pole and the posterior cingulate cortex contralateral to HS. Significant increase in connectivity was found between the non-epileptic AHC and midline structures, such as the anterior cingulate and dorsal medial prefrontal cortices, as well as the temporo-parietal junction bilaterally. Connectivity analyses also revealed a preserved positive connectivity between the non-epileptic and the epileptic AHC in the patients' group. SIGNIFICANCE: This study evidences epilepsy-induced changes in connectivity between the non-epileptic AHC and some limbic and default mode network areas. These changes in connectivity probably account for emotional, cognitive and decision-making impairments frequently observed in MTLE patients. The preserved neurometabolic connectivity between the non-epileptic and the epileptic AHC in MTLE patients is pivotal to explain the epilepsy-induced changes found in this study.

The conductances of molecular model junctions comprising a triazatriangulenium platform with or without an ethynyl spacer and an upright Zn-porphyrin are probed with a low-temperature scanning probe microscope. The platform alone is found to be highly conductive. The ethynyl-linked Zn-porphyrin moiety reduces the conductance by three orders of magnitude and leads to an unexpected, non-monotonous variation of the force that was measured simultaneously at the tip of the microscope. Density functional theory calculations show that this variation results from an induced tilting of the porphyrin.

Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes in vivo and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin., Competing Interests: Authors CF, AB, JS, KW, BK, RS, RK, JK, SB, DL, AS, MW, and EG were employed by the company Beiersdorf AG. LK and FL received consultation fees from Beiersdorf AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Falckenhayn, Bienkowska, Söhle, Wegner, Raddatz, Kristof, Kuck, Siegner, Kaufmann, Korn, Baumann, Lange, Schepky, Völzke, Kaderali, Winnefeld, Lyko and Grönniger.)

Aging is a complex process characterized by the gradual decline of physiological functions, leading to increased vulnerability to age-related diseases and reduced quality of life. Alterations in DNA methylation (DNAm) patterns have emerged as a fundamental characteristic of aged human skin, closely linked to the development of the well-known skin aging phenotype. These changes have been correlated with dysregulated gene expression and impaired tissue functionality. In particular, the skin, with its visible manifestations of aging, provides a unique model to study the aging process. Despite the importance of epigenetic age clocks in estimating biological age based on the correlation between methylation patterns and chronological age, a second-generation epigenetic age clock, which correlates DNAm patterns with a particular phenotype, specifically tailored to skin tissue is still lacking. In light of this gap, we aimed to develop a novel second-generation epigenetic age clock explicitly designed for skin tissue to facilitate a deeper understanding of the factors contributing to individual variations in age progression. To achieve this, we used methylation patterns from more than 370 female volunteers and developed the first skin-specific second-generation epigenetic age clock that accurately predicts the skin aging phenotype represented by wrinkle grade, visual facial age, and visual age progression, respectively. We then validated the performance of our clocks on independent datasets and demonstrated their broad applicability. In addition, we integrated gene expression and methylation data from independent studies to identify potential pathways contributing to skin age progression. Our results demonstrate that our epigenetic age clock, VisAgeX, specifically predicting visual age progression, not only captures known biological pathways associated with skin aging, but also adds novel pathways associated with skin aging., Competing Interests: Authors AB, JS, BK, SG, MW, EG, and CF are employed by Beiersdorf AG. FL and LK received consultation fees from Beiersdorf AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bienkowska, Raddatz, Söhle, Kristof, Völzke, Gallinat, Lyko, Kaderali, Winnefeld, Grönniger and Falckenhayn.)

The development of 'age clocks', machine learning models predicting age from biological data, has been a major milestone in the search for reliable markers of biological age and has since become an invaluable tool in aging research. However, beyond their unquestionable utility, current clocks offer little insight into the molecular biological processes driving aging, and their inner workings often remain non-transparent. Here we propose a new type of age clock, one that couples predictivity with interpretability of the underlying biology, achieved through the incorporation of prior knowledge into the model design. The clock, an artificial neural network constructed according to well-described biological pathways, allows the prediction of age from gene expression data of skin tissue with high accuracy, while at the same time capturing and revealing aging states of the pathways driving the prediction. The model recapitulates known associations of aging gene knockdowns in simulation experiments and demonstrates its utility in deciphering the main pathways by which accelerated aging conditions such as Hutchinson-Gilford progeria syndrome, as well as pro-longevity interventions like caloric restriction, exert their effects.

In recent years, reports of non-linear regulations in age- and longevity-associated biological processes have been accumulating. Inspired by methodological advances in precision medicine involving the integrative analysis of multi-omics data, we sought to investigate the potential of multi-omics integration to identify distinct stages in the aging progression from ex vivo human skin tissue. For this we generated transcriptome and methylome profiling data from suction blister lesions of female subjects between 21 and 76 years, which were integrated using a network fusion approach. Unsupervised cluster analysis on the combined network identified four distinct subgroupings exhibiting a significant age-association. As indicated by DNAm age analysis and Hallmark of Aging enrichment signals, the stages captured the biological aging state more clearly than a mere grouping by chronological age and could further be recovered in a longitudinal validation cohort with high stability. Characterization of the biological processes driving the phases using machine learning enabled a data-driven reconstruction of the order of Hallmark of Aging manifestation. Finally, we investigated non-linearities in the mid-life aging progression captured by the aging phases and identified a far-reaching non-linear increase in transcriptional noise in the pathway landscape in the transition from mid- to late-life.

Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed 'epigenetic drift', but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array-based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)