Celecoxib extends C. elegans lifespan via inhibition of insulin‐like signaling but not cyclooxygenase‐2 activity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86911/1/ACEL_688_sm_FigS1-S2-TableS1-S2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/86911/2/j.1474-9726.2011.00688.x.pd

Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

AMPK- mediated formation of stress granules is required for dietary restriction- induced longevity in Caenorhabditis elegans

Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR- 1::GFP and GTBP- 1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF- 1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK- eEF2K signaling is required for starvation and DR- induced SG formation but not heat shock. Moreover, our data suggest that this AMPK- eEF2K pathway- mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF- 1 signaling. Collectively, our findings unveil a novel role of SG formation in DR- induced longevity.In addition to heat stress, starvation and dietary restriction (DR) can activate stress granule (SG) formation in Caenorhabditis elegans. HSF- 1 and AMPK are two key regulators for the SG formations. HSF- 1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK- eEF2K pathway is required for starvation and DR- induced SG formation but not heat shock. Furthermore, AMPK- mediated SG formation contributes to DR- induced longevity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/1/acel13157-sup-0008-Figurelegends.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/2/acel13157-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/3/acel13157-sup-0006-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/4/acel13157-sup-0007-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/5/acel13157-sup-0005-FigS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/6/acel13157-sup-0003-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/7/acel13157.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/8/acel13157-sup-0002-FigS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/9/acel13157-sup-0004-FigS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155936/10/acel13157_am.pd

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Effective Actions and Phase Fluctuations in d-wave Superconductors

We study effective actions for order parameter fluctuations at low temperature in layered d-wave superconductors such as the cuprates. The order parameter lives on the bonds of a square lattice and has two amplitude and two phase modes associated with it. The low frequency spectral weights for amplitude and relative phase fluctuations is determined and found to be subdominant to quasiparticle contributions. The Goldstone phase mode and its coupling to density fluctuations in charged systems is treated in a gauge-invariant manner. The Gaussian phase action is used to study both the $c$-axis Josephson plasmon and the more conventional in-plane plasmon in the cuprates. We go beyond the Gaussian theory by deriving a coarse-grained quantum XY model, which incorporates important cutoff effects overlooked in previous studies. A variational analysis of this effective model shows that in the cuprates, quantum effects of phase fluctuations are important in reducing the zero temperature superfluid stiffness, but thermal effects are small for $T << T_c$.Comment: Some numerical estimates corrected and figures changed. to appear in PRB, Sept.1 (2000

Effective Mass of Composite Fermions and Fermionic Chern-Simons Theory in Temporal Gauge

The definitions of the effective mass of the composite fermion are discussed for the half-filled Landau level problem. In a recent work, Shankar and Murthy show a finite effective mass of the composite fermion by a canonical transformation while the perturbative calculation gives the logarithmic divergence of the effective mass at the Fermi surface. We will emphasize that the different definition of the effective mass has the different physical processes. The finite one could be defined for any momentum of the composite fermion while the divergence only appears at the Fermi surface. We work with the standard Halperin-Lee-Read model but in the temporal gauge. The advantage of this gauge to be employed is that the finite effective mass could be calculated in the Hartree-Fock approximation. Furthermore, it is precisely equal to the result that Shankar and Murthy obtained which is well-fit with the numerical calculation from the ground state energy analysis and a semi-classical estimation. However, if we consider the random phase approximation, one sees that the divergence of the effective mass of the quasiparticle at the Fermi surface emerges again no matter that we work on the temporal or Coulomb gauges. We develop an effective theory where the finite effective mass serves as a `bare' effective mass and show that the same divergence of the RPA effective mass. On the other hand, the correct behavior of the response functions in the small band mass limit could be seen clearly in the temporal gauge since there is a self-interaction among the magnetoplasmons.Comment: 27 pages,6 eps figure

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Still too far to walk: Literature review of the determinants of delivery service use

BACKGROUND: Skilled attendance at childbirth is crucial for decreasing maternal and neonatal mortality, yet many women in low- and middle-income countries deliver outside of health facilities, without skilled help. The main conceptual framework in this field implicitly looks at home births with complications. We expand this to include "preventive" facility delivery for uncomplicated childbirth, and review the kinds of determinants studied in the literature, their hypothesized mechanisms of action and the typical findings, as well as methodological difficulties encountered. METHODS: We searched PubMed and Ovid databases for reviews and ascertained relevant articles from these and other sources. Twenty determinants identified were grouped under four themes: (1) sociocultural factors, (2) perceived benefit/need of skilled attendance, (3) economic accessibility and (4) physical accessibility. RESULTS: There is ample evidence that higher maternal age, education and household wealth and lower parity increase use, as does urban residence. Facility use in the previous delivery and antenatal care use are also highly predictive of health facility use for the index delivery, though this may be due to confounding by service availability and other factors. Obstetric complications also increase use but are rarely studied. Quality of care is judged to be essential in qualitative studies but is not easily measured in surveys, or without linking facility records with women. Distance to health facilities decreases use, but is also difficult to determine. Challenges in comparing results between studies include differences in methods, context-specificity and the substantial overlap between complex variables. CONCLUSION: Studies of the determinants of skilled attendance concentrate on sociocultural and economic accessibility variables and neglect variables of perceived benefit/need and physical accessibility. To draw valid conclusions, it is important to consider as many influential factors as possible in any analysis of delivery service use. The increasing availability of georeferenced data provides the opportunity to link health facility data with large-scale household data, enabling researchers to explore the influences of distance and service quality

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence