Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-derived Mesenchymal Stem Cells

Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs). As assessed by ChIP-sequencing and RNA-sequencing analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, retinoid X receptor, and vitamin D receptor binding sites, whereas adipocyte differentiation favored PPARγ, retinoid X receptor, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg, and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment, as assessed by staining, gene expression, and ChIP-quantitative PCR analysis. The osteogenic default pathway may be subverted during pathological conditions, leading to skeletal fragility and increased marrow adiposity during aging, estrogen deficiency, and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies

Can uptake length in strams be determined by nutrient addition experiments? Results from an interbiome comparison study

Nutrient uptake length is an important parnmeter tor quantifying nutrient cycling in streams. Although nutrient tracer additions are the preierred method for measuring uptake length under ambient nutrient concentrations, short-term nutrient addition experiments have more irequently been used to estimate uptake length in streams. Theoretical analysis of the relationship between uptake length determined by nutrient addition experiments (Sw\u27) and uptake length determined by tracer additions (Sw)predicted that Sw\u27 should be consistently longer than 5, , and that the overestimate of uptake length by Sw( should be related to the level of nutrient addition above ambient concentrations and the degree of nutrient limitation. To test these predictions, we used data irom an interbiorne study of NH,- uptake length in which 15NH,- tracer and short-term NH,-a ddition experiments were performed in 10 streams using a uniform experimental approach. The experimental results largely contirmed the theoretical predictions: sw\u27 was consistently longer than Sw and Sw\u27:Sw ratios were directly related to the level of NH,- addition and to indicatvrs of N limitation. The experimentally derived Sw\u27:Sw, ratios were used with the theoretical results to infer the N limitation status of each stream. Together, the theoretical and experimental results showed the tracer experiments should be used whenever possible to determine nutrient uptake length in streams. Nutrient addition experiments may be useful for comparing uptake lengths between different streams or cliiferent times in the same stream. however, provided that nutrient additions are kept as low as possible and of similar miagnitude

Factors affecting ammonium uptake in streams - an inter-biome perspective

The Lotic Intersite Nitrogen experiment (LINX) was a coordinated study of the relationships between North American biomes and factors governing ammonium uptake in streams. Our objective was to relate inter-biome variability of ammonium uptake to physical, chemical and biological processes. 2. Data were collected from 11 streams ranging from arctic to tropical and from desert to rainforest. Measurements at each site included physical, hydraulic and chemical characteristics, biological parameters, whole-stream metabolism and ammonium uptake. Ammonium uptake was measured by injection of \u275~-ammonium and downstream measurements of 15N-ammonium concentration. 3. We found no general, statistically significant relationships that explained the variability in ammonium uptake among sites. However, this approach does not account for the multiple mechanisms of ammonium uptake in streams. When we estimated biological demand for inorganic nitrogen based on our measurements of in-stream metabolism, we found good correspondence between calculated nitrogen demand and measured assimilative nitrogen uptake. 4. Nitrogen uptake varied little among sites, reflecting metabolic compensation in streams in a variety of distinctly different biomes (autotrophic production is high where allochthonous inputs are relatively low and vice versa). 5. Both autotrophic and heterotrophic metabolism require nitrogen and these biotic processes dominate inorganic nitrogen retention in streams. Factors that affect the relative balance of autotrophic and heterotrophic metabolism indirectly control inorganic nitrogen uptake

A direct-to-drive neural data acquisition system

Driven by the increasing channel count of neural probes, there is much effort being directed to creating increasingly scalable electrophysiology data acquisition (DAQ) systems. However, all such systems still rely on personal computers for data storage, and thus are limited by the bandwidth and cost of the computers, especially as the scale of recording increases. Here we present a novel architecture in which a digital processor receives data from an analog-to-digital converter, and writes that data directly to hard drives, without the need for a personal computer to serve as an intermediary in the DAQ process. This minimalist architecture may support exceptionally high data throughput, without incurring costs to support unnecessary hardware and overhead associated with personal computers, thus facilitating scaling of electrophysiological recording in the future.National Institutes of Health (U.S.) (Grant 1DP1NS087724)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 2R44NS070453)National Institutes of Health (U.S.) (Grant R43MH101943)New York Stem Cell FoundationPaul Allen FoundationMassachusetts Institute of Technology. Media LaboratoryGoogle (Firm)United States. Defense Advanced Research Projects Agency (HR0011-14-2-0004)Hertz Foundation (Myhrvold Family Fellowship

The Kinetics of Specific Immune Responses in Rhesus Monkeys Inoculated with Live Recombinant BCG Expressing SIV Gag, Pol, Env, and Nef Proteins

AbstractDevelopment of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette–Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV

Analysis of sphingosine kinase activity in single natural killer cells from peripheral blood

Heterogeneity of sphingosine kinase (SK) pathway activity in natural killer (NK) cells may enable cells to respond effectively to a diverse array of pathogens as well as incipient tumor cells

The role of religion in the longer-range future, April 6, 7, and 8, 2006

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This conference that took place during April 6, 7, and 8, 2006. Co-organized by David Fromkin, Director, Frederick S. Pardee Center for the Study of the Longer-Range Future, and Ray L. Hart, Dean ad interim Boston University School of TheologyThe conference brought together some 40 experts from various disciplines to ponder upon the “great dilemma” of how science, religion, and the human future interact. In particular, different panels looked at trends in what is happening to religion around the world, questions about how religion is impacting the current political and economic order, and how the social dynamics unleashed by science and by religion can be reconciled.Carnegie Council on Ethics and International Affair

Providing information on mental well-being during audiological consultations : exploring barriers and facilitators using the COM-B model

OBJECTIVE : To identify the barriers and facilitators of hearing healthcare clinicians (HHC) providing information to audiology consumers on (i) the mental health impacts of hearing loss, and (ii) management options for improving mental well-being. DESIGN : A qualitative study using semi-structured individual and group interviews. Both the interview guide and the deductive process of data analysis were based on the COM-B model (Capabilities, Opportunities and Motivations required for Behaviour change). STUDY SAMPLE : Fifteen HHCs with between 2 and 25 years of clinical experience (mean 9.3). RESULTS : Psychological Capability barriers included lack of knowledge relating to mental health signs and symptoms, management options available, referral processes, and resources/tools to assist discussion of options. Social opportunity barriers included clients’ lack of openness to receive mental health-related information from their HHC. Automatic motivation factors included feeling uncomfortable and helpless when discussing mental health. Reflective motivation factors included clinician’s limiting beliefs concerning their role and responsibilities regarding provision of mental health support, and doubts about whether mental health services are truly beneficial for clients with hearing loss. CONCLUSION : Application of the COM-B model for behaviour change identified factors that need to be addressed to increase the provision of mental health information in the audiology setting.The Raine Medical Research Foundation through a Raine Priming grant.https://www.tandfonline.com/loi/iija20hj2023Speech-Language Pathology and Audiolog

Barriers and facilitators to asking adults with hearing loss about their emotional and psychological well-being : a COM-B analysis

OBJECTIVE : To explore the barriers and facilitators faced by hearing healthcare clinicians (HHCs) with respect to asking adults with hearing loss (HL) about their emotional well-being. DESIGN : This qualitative study was conducted using semi-structured individual interviews and focus groups. The interview topic guide was developed based on the COM-B model. STUDY SAMPLE : Fifteen HHCs of a single hearing services organisation in Western Australia across 13 clinic locations participated. RESULTS : Barriers and facilitators that may influence HHCs’ behaviour of routinely asking adults about their emotional well-being include having the knowledge and skills to ask about emotional well-being, forgetting to ask, awareness of the emotional impacts of HL, time and tools for asking, clients’ reactions to being asked, supportive peers, normalisation of discussions relating to emotional well-being, presence of significant others, emotions associated with asking, being in the habit of asking, reminders, beliefs about consequences and confidence or capabilities, and scope of audiology practice. CONCLUSIONS : Application of the COM-B model identified barriers in capabilities (e.g. knowledge), opportunities (e.g. tools), and motivation (e.g. beliefs about benefits of asking about emotions) that need to be addressed for HHCs to ask their clients about their emotional well-being.Raine Priming Grant from the Raine Medical Research Foundation, The University of Western Australia.https://www.tandfonline.com/loi/iija20hj2023Speech-Language Pathology and Audiolog