Charakterisierung von Apoptoseprozessen während der Differenzierung von humanen neuralen VM197-Progenitorzellen in vitro

Die humane neurale VM197-Progenitorzelllinie wurde bezüglich der Interkonnektivität von Wnt-gesteuerter neuraler Zelldeterminierung und Apoptose untersucht. Die Zelldifferenzierung ging mit der Aktivierung von pro- und anti-apoptotischen Proteinen und der Zunahme apoptotischen Zellverlustes einher. Differenzierte Zellen wiesen eine geringere Apoptosesuszeptibilität gegenüber proliferierenden Zellen auf. Beta-Catenin-Spaltung und eine geringere Apoptoserate nach GSK-3ß-Inhibierung in differenzierenden Zellen deuten auf eine Interkonnektivität von kanonischem Wnt-Signalweg und Apoptose hin.The human neural VM197 progenitor cell line was studied to elucidate the interconnectivity of Wnt-driven cell determination and apoptosis. The cell differentiation was accompanied by an activation of pro- and anti-apoptotic proteins and an increase of apoptotic cell loss. Differentiated cells showed a diminished apoptosis susceptibility compared to proliferating cells. Beta-catenin cleavage and a significantly decreased apoptosis rate after the inhibition of GSK-3ß in differentiated cells indicate an interconnectivity of the canonical Wnt-signaling pathway and apoptosis

Dynamics of quantum correlations and linear entropy in a multi-qubit-cavity system

We present a theoretical study of the relationship between entanglement and entropy in multi-qubit quantum optical systems. Specifically we investigate quantitative relations between the concurrence and linear entropy for a two-qubit mixed system, implemented as two two-level atoms interacting with a single-mode cavity field. The dynamical evolutions of the entanglement and entropy, are controlled via time-dependent cavity-atom couplings. Our theoretical findings lead us to propose an alternative measure of entanglement, which could be used to develop a much needed correlation measure for more general multi-partite quantum systems.Comment: New discussions on the generality of entanglement-entropy relationship, one new reference, and other minor changes. 10 pages, 6 figures, accepted for publication in J.Opt. B: "Special Issue on Fluctuations & Noise in Photonics & Quantum Optics.

Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

BACKGROUND: Mesenchymal stem cells (MSCs) show therapeutic efficacy in many different age-related degenerative diseases, including Alzheimer's disease. Very little is currently known about whether or not aging impacts the transplantation efficiency of MSCs. METHODS: In this study, we investigated the distribution of intravenously transplanted syngeneic MSCs derived from young and aged mice into young, aged, and transgenic APP/PS1 Alzheimer's disease mice. MSCs from male donors were transplanted into female mice and their distribution pattern was monitored by PCR using Y-chromosome specific probes. Biodistribution of transplanted MSCs in the brains of APP/PS1 mice was additionally confirmed by immunofluorescence and confocal microscopy. RESULTS: Four weeks after transplantation into young mice, young MSCs were found in the lung, axillary lymph nodes, blood, kidney, bone marrow, spleen, liver, heart, and brain cortex. In contrast, young MSCs that were transplanted into aged mice were only found in the brain cortex. In both young and aged mouse recipients, transplantation of aged MSCs showed biodistribution only in the blood and spleen. Although young transplanted MSCs only showed neuronal distribution in the brain cortex in young mice, they exhibited a wide neuronal distribution pattern in the brains of APP/PS1 mice and were found in the cortex, cerebellum, hippocampus, olfactory bulb, and brainstem. The immunofluorescent signal of both transplanted MSCs and resident microglia was robust in the brains of APP/PS1 mice. Monocyte chemoattractant-1 levels were lowest in the brain cortex of young mice and were significantly increased in APP/PS1 mice. Within the hippocampus, monocyte chemoattractant-1 levels were significantly higher in aged mice compared with younger and APP/PS1 mice. CONCLUSIONS: We demonstrate in vivo that MSC biodistribution post transplantation is detrimentally affected by aging and neuronal health. Aging of both the recipient and the donor MSCs used attenuates transplantation efficiency. Clinically, our data would suggest that aged MSCs should not be used for transplantation and that transplantation of MSCs into aged patients will be less efficacious

Using Photovoice to Understand Barriers to and Facilitators of Cardiovascular Health Among African American Adults and Adolescents, North Carolina, 2011–2012

IntroductionCardiovascular disease is the leading cause of death in the United States, and mortality rates are higher among African Americans than among people of other races/ethnicities. We aimed to understand how African American adults and adolescents conceptualize cardiovascular health and perceive related barriers and facilitators.MethodsThis qualitative study was conducted as formative research for a larger study, Heart Healthy Lenoir, which aimed to reduce cardiovascular disease disparities among African Americans in eastern North Carolina, part of the widely-known “stroke belt” that runs through the southeastern United States. Using photovoice, a community-based participatory research method, we conducted eight 90-minute photovoice sessions with 6 adults and 9 adolescents in Lenoir County, North Carolina. Topics for each discussion were selected by participants and reflected themes related to cardiovascular health promotion. All sessions were transcribed and coded using a data-driven, inductive approach.ResultsParticipants conceptualized cardiovascular health to have mental, spiritual, and social health dimensions. Given these broad domains, participants acknowledged many ecological barriers to cardiovascular health; however, they also emphasized the importance of personal responsibility. Facilitators for cardiovascular health included using social health (eg, family/community relationships) and spiritual health dimensions (eg, understanding one’s body and purpose) to improve health behaviors.ConclusionThe perspectives of African American adults and adolescents elicited through this formative research provided a strong foundation for Heart Healthy Lenoir’s ongoing engagement of community members in Lenoir County and development and implementation of its intervention to prevent cardiovascular disease

Where is the Faith? Using a CBPR Approach to Propose Adaptations to an Evidence-Based HIV Prevention Intervention for Adolescents in African American Faith Settings

African American adolescents are at increased risk for HIV/AIDS. Using a community-based participatory research approach, we engaged three black churches in adapting an evidence-based HIV prevention intervention, Focus on Youth (FOY)+ImPACT, for faith settings. To identify potential adaptations to increase FOY's relevance, utility, and efficacy for faith settings, we conducted eight focus groups pre- and post-intervention. Recommendations for maintaining FOY's core elements and enhancing its cultural authenticity include the following: incorporating faith tools, building pastor capacity, strengthening parent-child communication skills, and expanding social support for parents and youth. Engaging faith communities in adapting and implementing evidence-based HIV prevention programs could reduce HIV/AIDS disparities

Genetic determinants of fungi-induced ROS production are associated with the risk of invasive pulmonary aspergillosis

© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Reactive oxygen species (ROS) are an essential component of the host defense against fungal infections. However, little is known about how common genetic variation affects ROS-mediated antifungal host defense. In the present study, we investigated the genetic factors that regulate ROS production capacity in response to the two human fungal pathogens: Candida albicans and Aspergillus fumigatus. We investigated fungal-stimulated ROS production by immune cells isolated from a population-based cohort of approximately 200 healthy individuals (200FG cohort), and mapped ROS-quantitative trait loci (QTLs). We identified several genetic loci that regulate ROS levels (P < 9.99 × 10-6), with some of these loci being pathogen-specific, and others shared between the two fungi. These ROS-QTLs were investigated for their influence on the risk of invasive pulmonary aspergillosis (IPA) in a disease relevant context. We stratified hematopoietic stem-cell transplant (HSCT) recipients based on the donor's SNP genotype and tested their impact on the risk of IPA. We identified rs4685368 as a ROS-QTL locus that was significantly associated with an increased risk of IPA after controlling for patient age and sex, hematological malignancy, type of transplantation, conditioning regimen, acute graft-versus-host-disease grades III-IV, and antifungal prophylaxis. Collectively, this data provides evidence that common genetic variation can influence ROS production capacity, and, importantly, the risk of developing IPA among HSCT recipients. This evidence warrants further research for patient stratification based on the genetic profiling that would allow the identifications of patients at high-risk for an invasive fungal infection, and who would benefit the most from a preventive strategy.This study was supported by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 847507 (HDM-FUN). MGN was supported by an ERC Advanced grant (833247) and a Spinoza grant of the Netherlands Association for Scientific Research. VK was supported by a Research Grant [2017] of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Hypatia tenure track grant. AC was supported by the Fundação para a Ciência e a Tecnologia (FCT) (UIDB/50026/2020 and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000039), and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003. CC was supported by FCT (CEECIND/04058/2018 and PTDC/SAU-SER/29,635/2017) and the Gilead Research Scholars Program – Antifungals. SMG was the recipient of a PhD fellowship funded by FCT (SFRH/BD/136,814/2018). MSG was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft - DFG) Emmy Noether Program (project no. 434385622/GR 5617/1-1).info:eu-repo/semantics/publishedVersio

Cosmicflows-4

With Cosmicflows-4, distances are compiled for 55,877 galaxies gathered into 38,065 groups. Eight methodologies are employed, with the largest numbers coming from the correlations between the photometric and kinematic properties of spiral galaxies (TF) and elliptical galaxies (FP). Supernovae that arise from degenerate progenitors (SNIa) are an important overlapping component. Smaller contributions come from distance estimates from the surface brightness fluctuations of elliptical galaxies (SBF) and the luminosities and expansion rates of core collapse supernovae (SNII). Cepheid Period-Luminosity Relation (CPLR) and Tip of the Red Giant Branch (TRGB) observations founded on local stellar parallax measurements along with the geometric maser distance to NGC 4258 provide the absolute scaling of distances. The assembly of galaxies into groups is an important feature of the study in facilitating overlaps between methodologies. Merging between multiple contributions within a methodology and between methodologies is carried out with Bayesian Markov chain Monte Carlo procedures. The final assembly of distances is compatible with a value of the Hubble constant of $H_0=75.0$ km s$^{-1}$ Mpc$^{-1}$ with the small statistical error $\pm$ $0.8$ km s$^{-1}$ Mpc$^{-1}$ but a large potential systematic error ~3 km s$^{-1}$ Mpc$^{-1}$. Peculiar velocities can be inferred from the measured distances. The interpretation of the field of peculiar velocities is complex because of large errors on individual components and invites analyses beyond the scope of this study.Comment: 38 pages, 24 figures. catalogs available at edd.ifa.hawaii.edu. Accepted to Ap

Gut microbial co-abundance networks show specificity in inflammatory bowel disease and obesity

The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease

Newly discovered deep-branching marine plastid lineages are numerically rare but globally distributed

Ocean surface warming is resulting in an expansion of stratified, low-nutrient environments, a process referred to as ocean desertification 1. A challenge for assessing the impact of these changes is the lack of robust baseline information on the biological communities that carry out marine photosynthesis. Phytoplankton perform half of global biological CO2 uptake, fuel marine food chains, and include diverse eukaryotic algae that have photosynthetic organelles (plastids) acquired through multiple evolutionary events 1–3. While amassing data from ocean ecosystems for the Baselines Initiative (6,177 near full-length 16S rRNA gene sequences and 9.4 million high-quality 16S V1-V2 amplicons) we identified two deep-branching plastid lineages based on 16S rRNA gene data. The two lineages have global distributions, but do not correspond to known phytoplankton. How the newly discovered phytoplankton lineages contribute to food chains and vertical carbon export to the deep sea remains unknown, but their prevalence in expanding, low nutrient surface waters suggests they will have a role in future oceans. © 2017 The Author(s