Iron limitation of a springtime bacterial and phytoplankton community in the Ross Sea : implications for vitamin B12 nutrition

© The Author(s), 2011. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums. The definitive version was published in Frontiers in Microbiology 2 (2011): 160, doi:10.3389/fmicb.2011.00160.The Ross Sea is home to some of the largest phytoplankton blooms in the Southern Ocean. Primary production in this system has previously been shown to be iron limited in the summer and periodically iron and vitamin B12 colimited. In this study, we examined trace metal limitation of biological activity in the Ross Sea in the austral spring and considered possible implications for vitamin B12 nutrition. Bottle incubation experiments demonstrated that iron limited phytoplankton growth in the austral spring while B12, cobalt, and zinc did not. This is the first demonstration of iron limitation in a Phaeocystis antarctica-dominated, early season Ross Sea phytoplankton community. The lack of B12 limitation in this location is consistent with previous Ross Sea studies in the austral summer, wherein vitamin additions did not stimulate P. antarctica growth and B12 was limiting only when bacterial abundance was low. Bottle incubation experiments and a bacterial regrowth experiment also revealed that iron addition directly enhanced bacterial growth. B12 uptake measurements in natural water samples and in an iron fertilized bottle incubation demonstrated that bacteria serve not only as a source for vitamin B12, but also as a significant sink, and that iron additions enhanced B12 uptake rates in phytoplankton but not bacteria. Additionally, vitamin uptake rates did not become saturated upon the addition of up to 95 pM B12. A rapid B12 uptake rate was observed after 13 min, which then decreased to a slower constant uptake rate over the next 52 h. Results from this study highlight the importance of iron availability in limiting early season Ross Sea phytoplankton growth and suggest that rates of vitamin B12 production and consumption may be impacted by iron availability.This research was supported by NSF grants OCE-0752291, OPP-0440840, OPP-0338097, OPP-0338164, ANT-0732665, OCE-0452883, and OCE-1031271, the Center for Microbial Oceanography Research and Education (CMORE) and a National Science Foundation (NSF) Graduate Research Fellowship (2007037200) and an Environmental Protection Agency STAR Fellowship to EMB (F6E20324)

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffnesschondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process

Memory Aging: Deficits, Beliefs, and Interventions

Of all mental faculties, memory is unique. It defines who we are and places our lives on a narrative continuum from birth to death. It helps to structure our days, it guides our daily tasks and goals, and it provides pleasurable interludes as we anticipate the future and recall the past. As a core, defining feature of the self (Birren & Schroots, 2006), memory takes on heightened meaning as we age. In the face of other losses that accumulate with age, memory can serve to preserve our sense of self and place in time. In normal aging, memory loss is minor and relatively inconsequential to functional well-being, other than passing annoyance at not being able to retrieve a name or a location from time to time. In non-normal or pathological aging, as characterized by Alzheimer\u27s disease (AD), the loss of memory is severe and debilitating. In addition to functional disability, people with AD ultimately lose their sense of self. Connections to the past, to current events and relationships, and to what the future holds fade and ultimately disappear. Such a bleak fate for the self continues to spur researchers to look for causes and cures for normal and pathological memory failure. Current cutting-edge research examines the transition from normal to pathological memory aging, with particular emphasis on mild cognitive impairment (MCI) as a transitional phase and as an independent risk factor for AD. Concurrent efforts have focused on developing effective intervention and treatment programs aimed at biological, psychosocial, and cognitive levels. This chapter highlights current research on normative memory change with age, with a focus on self-regulation, self efficacy, and memory maintenance and maximization. We also look at the special contexts of mild cognitive impairment and Alzheimer\u27s disease, and close with an eye toward future directions in theory, research, and intervention

The effects of a workplace intervention on employees’ cortisol awakening response

Work-related stressors are known to adversely affect employees’ stress physiology, including the cortisol awakening response (CAR)–or the spike in cortisol levels shortly after people wake up that aids in mobilizing energy. A flat or blunted CAR has been linked to chronic stress and burnout. This daily diary study tested the effects of a workplace intervention on employed parents’ CAR. Specifically, we tested whether the effects of the intervention on CAR were moderated by the type of days (workday versus non-work day). Data came from 94 employed parents from an information technology firm who participated in the baseline and 12-month diurnal cortisol components of the Work, Family, and Health Study, a group-randomized field experiment. The workplace intervention was designed to reduce work-family conflict (WFC) and implemented after the baseline data collection. Diurnal salivary cortisol was collected on 4 days at both baseline and 12 months. Multilevel modeling revealed that the intervention significantly increased employees’ CAR at 12 months on non-workdays, but this was not evident on workdays or for employees in the usual practice condition. The results provide evidence that the intervention was effective in enhancing employees’ biological stress physiology particularly during opportunities for recovery that are more likely to occur on non-work days.National Institute on Aging (U01AG027669)Work, Family & Health Network (U01HD051217)Work, Family & Health Network (U01HD051218)Work, Family & Health Network (U01HD051256)Work, Family & Health Network (U01HD051276)U.S. Army Research Institute for the Behavioral and Social SciencesNational Institute for Occupational Safety and Health (U010H008788)Alfred P. Sloan Foundation (2004-12-4)William T. Grant Foundation (9844)National Institutes of Health (U.S.) (Penn State General Clinical Research Center. Grant M01-RR-10732

Preliminary Findings from a Pediatric Physical Activity Program for Children with Cancer

It is critical for pediatric patients diagnosed with cancer to engage in physical activity (PA) as it is associated with positive psychosocial outcomes and may improve physical function. However, physical activity opportunities for pediatric cancer patients are limited. PURPOSE: To test the feasibility and adherence of pediatric cancer patients to a virtual PA program. METHODS: Pediatric patients undergoing cancer treatment were referred to the Pediatric Physical Activity program (PePA) by the Children’s Hospital’s oncology team using rolling recruitment. The target sample size was 20-25 patients. Patients enrolled in an online 12-week PA intervention with similar-aged peers (2x/week, 60 min/session). Patients completed surveys which shared their hobbies and interests. They were given PA equipment (i.e., yoga ball, mat). Trained undergraduate Kinesiology students designed and delivered the PA lessons which included yoga, dancing, calisthenics and Pilates. PA duration (visual inspection of recorded sessions, system for observing fitness instruction time, SOFIT), intensity (wrist-based heart rate monitors) and focus group data were used to assess program feasibility. RESULTS: Nine patients enrolled in the study (5, 5-7 years-olds; 4, 13-16 year-olds). One patient from each group completed 95% and 79% of the 24 sessions, respectively. These 2 patients reported improved balance and enjoyment of the program. PA leaders led the 5-7-year-old and 13-16-year-old groups through 27.6±4.9 and 33.0±9.4 minutes of PA, respectively. Average PA intensity was 26±6% heart rate reserve (HRR) and varied based upon activity. Patients rated their perceived exertion (RPE) of the PA as 2-7 on a scale of 1-10. During the session, children aged 5-7 years and 13-16 years engaged in 14.6±9.1 and 27.2±14.4 minutes of fitness, respectively (SOFIT coding). Three-fourths through the program, the duration for the 5-7 year olds was reduced to 45 minutes to match energy levels. Patients and parent-proxies of the younger children reported that they liked the session duration and type of PA performed. CONCLUSION: PA intensity fell at the lower end of the recommended 30-45% HRR range for adult patients undergoing cancer treatment. Program adherence was difficult to achieve, but those who completed the program reported physical benefit

N17 Modifies mutant Huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice.

The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington's disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant huntingtin (mHTT) mediates its nuclear exclusion in cultured cells. Here, we test whether N17 could be a molecular determinant of nuclear mHTT pathogenesis in vivo. BAC transgenic mice expressing mHTT lacking the N17 domain (BACHD-ΔN17) show dramatically accelerated mHTT pathology exclusively in the nucleus, which is associated with HD-like transcriptionopathy. Interestingly, BACHD-ΔN17 mice manifest more overt disease-like phenotypes than the original BACHD mice, including body weight loss, movement deficits, robust striatal neuron loss, and neuroinflammation. Mechanistically, N17 is necessary for nuclear exclusion of small mHTT fragments that are part of nuclear pathology in HD. Together, our study suggests that N17 modifies nuclear pathogenesis and disease severity in HD mice by regulating subcellular localization of known nuclear pathogenic mHTT species

Mobilization of Intracellular Copper Stores by the Ctr2 Vacuolar Copper Transporter

Copper plays an essential role in processes including signaling to the transcription and protein trafficking machinery, oxidative phosphorylation, iron mobilization, neuropeptide maturation, and normal development. Whereas much is known about intracellular mobilization of ions such as calcium, little information is available on how eukaryotic cells mobilize intracellular copper stores. We describe a mechanism by which the Saccharomyces cerevisiae Ctr2 protein provides bioavailable copper via mobilization of intracellular copper stores. Whereas Ctr2 exhibits structural similarity to the Ctr1 plasma membrane copper importer, microscopic and biochemical fractionation studies localize Ctr2 to the vacuole membrane. We demonstrate that Ctr2 mobilizes vacuolar copper stores in a manner dependent on amino acid residues conserved between the Ctr1 and Ctr2 copper transport family and that ctr2∆ mutants hyper-accumulate vacuolar copper. Furthermore, a Ctr2 mutant that is mislocalized to the plasma membrane stimulates extracellular copper uptake, supporting a direct role for Ctr2 in copper transport across membranes. These studies identify a novel mechanism for copper mobilization and suggest that organisms cope with copper deprivation via the use of intracellular vesicular stores

Effects of bone marrow‐derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF‐α, IL‐1β, and IFN‐γ

The acute respiratory distress syndrome (ARDS) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in animal models of ARDS, and their benefits occur in part through interactions with alveolar type II (ATII) cells. However, the effects that MSCs have on human ATII cells have not been well studied. Using previously published microarray data, we performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to proinflammatory cytokines plus MSCs. Findings were validated by qPCR. Alveolar type II cells differentially expressed hundreds of genes when exposed either to proinflammatory cytokines or to proinflammatory cytokines plus MSCs. Stimulation with proinflammatory cytokines increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance. Some of these changes, including expression of some cytokines and genes related to surfactant, were reversed by exposure to MSCs. In addition, MSCs induced upregulation of other potentially beneficial genes, such as those related to extracellular matrix remodeling. We confirmed several of these gene expression changes by qPCR. Thus, ATII cells downregulate genes associated with surfactant and alveolar fluid clearance when exposed to inflammatory cytokines, and mesenchymal stromal cells partially reverse many of these gene expression changes.Mesenchymal stromal cells (MSCs) have therapeutic potential for the acute respiratory distress syndrome, and their benefits occur in part through interactions with alveolar type II (ATII) cells. We performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to CytoMix plus MSCs. Stimulation with CytoMix increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance, and several gene expression changes were reversed by exposure to MSCs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145579/1/phy213831_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145579/2/phy213831.pd

Addressing the Supportive Transportation Challenges of Community-Residing Older Adults

The ability to get to where you want to go, when you want to go there is a key factor for aging-in-place in our communities. It is often taken for granted until that ability is compromised. The informal network of family and friends, if it exists, is not likely to be a sustainable transportation alternative for persons with cognitive impairment or for older adults with limitations that may not fit eligibility criteria for senior transportation services, where they exist. The purpose of this study was to investigate the potential of communities to address the specialized supportive mobility needs of community-residing older adults. A major conclusion to emerge from the research is the connection of mobility to healthcare