589 research outputs found
Obstetric and long-term kidney outcomes in renal transplant recipients: a 40 year single-centre study
Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A caseâcohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of â„20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function
Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
A disruptive approach to therapeutic discovery and development is required in order to significantly improve the success rate of drug discovery for central nervous system (CNS) disorders. In this review, we first assess the key factors contributing to the frequent clinical failures for novel drugs. Second, we discuss cancer translational research paradigms that addressed key issues in drug discovery and development and have resulted in delivering drugs with significantly improved outcomes for patients. Finally, we discuss two emerging technologies that could improve the success rate of CNS therapies: human induced pluripotent stem cell (hiPSC)-based studies and multiscale biology models. Coincident with advances in cellular technologies that enable the generation of hiPSCs directly from patient blood or skin cells, together with methods to differentiate these hiPSC lines into specific neural cell types relevant to neurological disease, it is also now possible to combine data from large-scale forward genetics and post-mortem global epigenetic and expression studies in order to generate novel predictive models. The application of systems biology approaches to account for the multiscale nature of different data types, from genetic to molecular and cellular to clinical, can lead to new insights into human diseases that are emergent properties of biological networks, not the result of changes to single genes. Such studies have demonstrated the heterogeneity in etiological pathways and the need for studies on model systems that are patient-derived and thereby recapitulate neurological disease pathways with higher fidelity. In the context of two common and presumably representative neurological diseases, the neurodegenerative disease Alzheimerâs Disease (AD), and the psychiatric disorder schizophrenia (SZ), we propose the need for, and exemplify the impact of, a multiscale biology approach that can integrate panomic, clinical, imaging, and literature data in order to c
An efficient platform for astrocyte differentiation from human induced pluripotent stem cells
Summary: Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30Â days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. : Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. Keywords: human induced pluripotent stem cell, iPSC, astrocyt
Light-particle emission from the fissioning nuclei 126Ba, 188Pt and (266,272,278)/110: theoretical predictions and experimental results
We present a comparison of our model treating fission dynamics in conjunction
with light-particle (n, p, alpha) evaporation with the available experimental
data for the nuclei 126Ba, 188Pt and three isotopes of the element Z=110. The
dynamics of the symmetric fission process is described through the solution of
a classical Langevin equation for a single collective variable characterizing
the nuclear deformation along the fission path. A microscopic approach is used
to evaluate the emission rates for pre-fission light particles.
Entrance-channel effects are taken into account by generating an initial spin
distribution of the compound nucleus formed by the fusion of two deformed
nuclei with different relative orientations
Structure of Be probed via secondary beam reactions
The low-lying level structure of the unbound neutron-rich nucleus Be
has been investigated via breakup on a carbon target of secondary beams of
B at 35 MeV/nucleon. The coincident detection of the beam velocity
Be fragments and neutrons permitted the invariant mass of the
Be+ and Be++ systems to be reconstructed. In the case of
the breakup of B, a very narrow structure at threshold was observed in
the Be+ channel. Contrary to earlier stable beam fragmentation
studies which identified this as a strongly interacting -wave virtual state
in Be, analysis here of the Be++ events demonstrated that
this was an artifact resulting from the sequential-decay of the
Be(2) state. Single-proton removal from B was found to
populate a broad low-lying structure some 0.70 MeV above the neutron-decay
threshold in addition to a less prominent feature at around 2.4 MeV. Based on
the selectivity of the reaction and a comparison with (0-3)
shell-model calculations, the low-lying structure is concluded to most probably
arise from closely spaced J=1/2 and 5/2 resonances
(E=0.400.03 and 0.85 MeV), whilst the broad
higher-lying feature is a second 5/2 level (E=2.350.14 MeV). Taken
in conjunction with earlier studies, it would appear that the lowest 1/2
and 1/2 levels lie relatively close together below 1 MeV.Comment: 14 pages, 13 figures, 2 tables. Accepted for publication in Physical
Review
Three-body correlations in Borromean halo nuclei
Three-body correlations in the dissociation of two-neutron halo nuclei are
explored using a technique based on intensity interferometry and Dalitz plots.
This provides for the combined treatment of both the n-n and core-n
interactions in the exit channel. As an example, the breakup of 14Be into
12Be+n+n by Pb and C targets has been analysed and the halo n-n separation
extracted. A finite delay between the emission of the neutrons in the reaction
on the C target was observed and is attributed to 13Be resonances populated in
sequential breakup.Comment: 5 pages, 4 figures, submitted to PR
The detection of neutron clusters
A new approach to the production and detection of bound neutron clusters is
presented. The technique is based on the breakup of beams of very neutron-rich
nuclei and the subsequent detection of the recoiling proton in a liquid
scintillator. The method has been tested in the breakup of 11Li, 14Be and 15B
beams by a C target. Some 6 events were observed that exhibit the
characteristics of a multineutron cluster liberated in the breakup of 14Be,
most probably in the channel 10Be+4n. The various backgrounds that may mimic
such a signal are discussed in detail.Comment: 11 pages, 12 figures, LPCC 01-1
Rapid Cellular Turnover in Adipose Tissue
It was recently shown that cellular turnover occurs within the human adipocyte population. Through three independent experimental approaches â dilution of an inducible histone 2B-green fluorescent protein (H2BGFP), labeling with the cell cycle marker Ki67 and incorporation of BrdU â we characterized the degree of cellular turnover in murine adipose tissue. We observed rapid turnover of the adipocyte population, finding that 4.8% of preadipocytes are replicating at any time and that between 1â5% of adipocytes are replaced each day. In light of these findings, we suggest that adipose tissue turnover represents a possible new avenue of therapeutic intervention against obesity
- âŠ