143 research outputs found
Cell death and degeneration in the symbiotic dinoflagellates of the coral Stylophora pistillata during bleaching
Rising sea temperatures are increasing the incidences of mass coral bleaching (the dissociation
of the coralβalgal symbiosis) and coral mortality. In this study, the effects of bleaching
(induced by elevated light and temperature) on the condition of symbiotic dinoflagellates (Symbiodinium
sp.) within the tissue of the hard coral Stylophora pistillata (Esper) were assessed using a suite
of techniques. Bleaching of S. pistillata was accompanied by declines in the maximum potential
quantum yield of photosynthesis (Fv/Fm, measured using pulse amplitude modulated [PAM] fluorometry),
an increase in the number of Sytox-green-stained algae (indicating compromised algal membrane
integrity and cell death), an increase in 2β,7β-dichlorodihydrofluroscein diacetate (H2DCFDA)-
stained algae (indicating increased oxidative stress), as well as ultrastructural changes (vacuolisation,
losses of chlorophyll, and an increase in accumulation bodies). Algae expelled from S. pistillata
exhibited a complete disorganisation of cellular contents; expelled cells contained only amorphous
material. In situ samples taken during a natural mass coral bleaching event on the Great Barrier Reef
in February 2002 also revealed a high number of Sytox-labelled algae cells in symbio. Dinoflagellate\ud
degeneration during bleaching seems to be similar to the changes resulting from senescence-phase
cell death in cultured algae. These data support a role for oxidative stress in the mechanism of coral
bleaching and highlight the importance of algal degeneration during the bleaching of a reef coral
Identification of senescence and death in Emiliania huxleyi and Thalassiosira pseudonana: Cell staining, chlorophyll alterations, and dimethylsulfoniopropionate (DMSP) metabolism
We measured membrane permeability, hydrolytic enzyme, and caspase-like activities using fluorescent cell stains to document changes caused by nutrient exhaustion in the coccolithophore Emiliania huxleyi and the diatom Thalassiosira pseudonana, during batch-culture nutrient limitation. We related these changes to cell death, pigment alteration, and concentrations of dimethylsulfide (DMS) and dimethylsulfoniopropionate (DMSP) to assess the transformation of these compounds as cell physiological condition changes. E. huxleyi persisted for 1 month in stationary phase; in contrast, T. pseudonana cells rapidly declined within 10 d of nutrient depletion. T. pseudonana progressively lost membrane integrity and the ability to metabolize 5-chloromethylfluorescein diacetate (CMFDA; hydrolytic activity), whereas E. huxleyi developed two distinct CMFDA populations and retained membrane integrity (SYTOX Green). Caspase-like activity appeared higher in E. huxleyi than in T. pseudonana during the post-growth phase, despite a lack of apparent mortality and cell lysis. Photosynthetic pigment degradation and transformation occurred in both species after growth; chlorophyll a (Chl a) degradation was characterized by an increase in the ratio of methoxy Chl a : Chl a in T. pseudonana but not in E. huxleyi, and the increase in this ratio preceded loss of membrane integrity. Total DMSP declined in T. pseudonana during cell death and DMS increased. In contrast, and in the absence of cell death, total DMSP and DMS increased in E. huxleyi. Our data show a novel chlorophyll alteration product associated with T. pseudonana death, suggesting a promising approach to discriminate nonviable cells in nature
Dynamics of broken symmetry lambda phi^4 field theory
We study the domain of validity of a Schwinger-Dyson (SD) approach to
non-equilibrium dynamics when there is broken symmetry. We perform exact
numerical simulations of the one- and two-point functions of lambda phi^4 field
theory in 1+1 dimensions in the classical domain for initial conditions where <
phi(x) > not equal to 0. We compare these results to two self-consistent
truncations of the SD equations which ignore three-point vertex function
corrections. The first approximation, which sets the three-point function to
one (the bare vertex approximation (BVA)) gives an excellent description for <
phi(x) > = phi(t). The second approximation which ignores higher in 1/N
corrections to the 2-PI generating functional (2PI -1/N expansion) is not as
accurate for phi(t). Both approximations have serious deficiencies in
describing the two-point function when phi(0) > .4.Comment: 10 pages, 6 figure
Associations between pedometer determined physical activity and adiposity in children and adolescents
Objective: The present review sought to examine the evidence on the associations between pedometer-determined physical activity and adiposity. Design: Of 304 potentially eligible articles, 36 were included. A search for observational studies was carried out using Cochrane Library (CENTRAL), the OVID (MEDLINE, Embase, and PsycINFO), EBSCOhost (Sportdiscus), and PEDro database from their commenced to July 2015. Of 304 potentially eligible articles, 36 were included. Results: Most studies (30/36; 83%) were cross sectional and all used proxies for adiposity, such as body mass index (BMI) or BMI z-score as the outcome measure. Few studies (2/36; 6%) focused on preschool children. There was consistent evidence of negative associations between walking and adiposity; significant negative associations were observed in 72% (26/36) of studies overall. Conclusions: The present review supports the hypothesis that higher levels of walking are protective against child and adolescent obesity. However, prospective longitudinal studies are warranted; there is a need for more research on younger children and for more βdose-responseβ evidence
Quantum dynamics of phase transitions in broken symmetry field theory
We perform a detailed numerical investigation of the dynamics of broken
symmetry field theory in 1+1 dimensions using a
Schwinger-Dyson equation truncation scheme based on ignoring vertex
corrections. In an earlier paper, we called this the bare vertex approximation
(BVA). We assume the initial state is described by a Gaussian density matrix
peaked around some non-zero value of and .Comment: 28 pages, 21 figures; ver 2 -- additional comments on the nature of
the phase transition in 1+1 dimension
Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli
Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis
Protection of Stem Cell-Derived Lymphocytes in a Primate AIDS Gene Therapy Model after In Vivo Selection
Background: There is currently no effective AIDS vaccine, emphasizing the importance of developing alternative therapies. Recently, a patient was successfully transplanted with allogeneic, naturally resistant CCR5-negative (CCR5 delta 32) cells, setting the stage for transplantation of naturally resistant, or genetically modified stem cells as a viable therapy for AIDS. Hematopoietic stem cell (HSC) gene therapy using vectors that express various anti-HIV transgenes has also been attempted in clinical trials, but inefficient gene transfer in these studies has severely limited the potential of this approach. Here we evaluated HSC gene transfer of an anti-HIV vector in the pigtailed macaque (Macaca nemestrina) model, which closely models human transplantation. Methods and Findings: We used lentiviral vectors that inhibited both HIV-1 and simian immunodeficiency virus (SIV)/HIV-1 (SHIV) chimera virus infection, and also expressed a P140K mutant methylguanine methyltransferase (MGMT) transgene to select gene-modified cells by adding chemotherapy drugs. Following transplantation and MGMT-mediated selection we demonstrated transgene expression in over 7% of stem-cell derived lymphocytes. The high marking levels allowed us to demonstrate protection from SHIV in lymphocytes derived from gene-modified macaque long-term repopulating cells that expressed an HIV-1 fusion inhibitor. We observed a statistically significant 4-fold increase of gene-modified cells after challenge of lymphocytes from one macaque that received stem cells transduced with an anti-HIV vector (p<0.02, Student's t-test), but not in lymphocytes from a macaque that received a control vector. We also established a competitive repopulation assay in a second macaque for preclinical testing of promising anti-HIV vectors. The vectors we used were HIV-based and thus efficiently transduce human cells, and the transgenes we used target HIV-1 genes that are also in SHIV, so our findings can be rapidly translated to the clinic. Conclusions: Here we demonstrate the ability to select protected HSC-derived lymphocytes in vivo in a clinically relevant nonhuman primate model of HIV/SHIV infection. This approach can now be evaluated in human clinical trials in AIDS lymphoma patients. In this patient setting, chemotherapy would not only kill malignant cells, but would also increase the number of MGMTP140K-expressing HIV-resistant cells. This approach should allow for high levels of HIV-protected cells in AIDS patients to evaluate AIDS gene therapy
Progress in gene therapy for neurological disorders
Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy
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