557 research outputs found
The Human Cytomegalovirus Chemokine vCXCL-1 Modulates Normal Dissemination Kinetics of Murine Cytomegalovirus In Vivo
Human cytomegalovirus (HCMV) is a betaherpesvirus that is a significant pathogen within newborn and immunocompromised populations. Morbidity associated with HCMV infection is the consequence of viral dissemination. HCMV has evolved to manipulate the host immune system to enhance viral dissemination and ensure long-term survival within the host. The immunomodulatory protein vCXCL-1, a viral chemokine functioning primarily through the CXCR2 chemokine receptor, is hypothesized to attract CXCR2+ neutrophils to infection sites, aiding viral dissemination. Neutrophils harbor HCMV in vivo; however, the interaction between vCXCL-1 and the neutrophil has not been evaluated in vivo. Using the mouse model and mouse cytomegalovirus (MCMV) infection, we show that murine neutrophils harbor and transfer infectious MCMV and that virus replication initiates within this cell type. Utilizing recombinant MCMVs expressing vCXCL-1 from the HCMV strain (Toledo), we demonstrated that vCXCL-1 significantly enhances MCMV dissemination kinetics. Through cellular depletion experiments, we observe that neutrophils impact dissemination but that overall dissemination is largely neutrophil independent. This work adds neutrophils to the list of innate cells (i.e., dendritic and macrophages/monocytes) that contribute to MCMV dissemination but refutes the hypothesis that neutrophils are the primary cell responding to vCXCL-1
Superhumps in Cataclysmic Binaries. XXV. q_crit, epsilon(q), and Mass-Radius
We report on successes and failures in searching for positive superhumps in
cataclysmic variables, and show the superhumping fraction as a function of
orbital period. Basically, all short-period systems do, all long-period systems
don't, and a 50% success rate is found at P_orb=3.1+-0.2 hr. We can use this to
measure the critical mass ratio for the creation of superhumps. With a
mass-radius relation appropriate for cataclysmic variables, and an assumed mean
white-dwarf mass of 0.75 M_sol, we find a mass ratio q_crit=0.35+-0.02.
We also report superhump studies of several stars of independently known mass
ratio: OU Virginis, XZ Eridani, UU Aquarii, and KV UMa (= XTE J1118+480). The
latter two are of special interest, because they represent the most extreme
mass ratios for which accurate superhump measurements have been made. We use
these to improve the epsilon(q) calibration, by which we can infer the elusive
q from the easy-to-measure epsilon (the fractional period excess of P_superhump
over P_orb). This relation allows mass and radius estimates for the secondary
star in any CV showing superhumps. The consequent mass-radius law shows an
apparent discontinuity in radius near 0.2 M_sol, as predicted by the disrupted
magnetic braking model for the 2.1-2.7 hour period gap. This is effectively the
"empirical main sequence" for CV secondaries.Comment: PDF, 45 pages, 9 tables, 12 figures; accepted, in press, to appear
November 2005, PASP; more info at http://cba.phys.columbia.edu
Functionalized gold nanorod nanocomposite system to modulate differentiation of human mesenchymal stem cells into neural-like progenitors
A 2D multifunctional nanocomposite system of gold nanorods (AuNRs) was developed. Gold nanorods were functionalized via polyethylene glycol with a terminal amine, and, were characterized using transmission and scanning electron microscopy, ultra violet-visible and X-ray photoelectron spectroscopy, and Zeta-potential. The system was cytocompatible to and maintained the integrity of Schwann cells. The neurogenic potential of adipose tissue – derived human mesenchymal stem cells (hMSCs) was evaluated in vitro. The expression pattern and localization of Vimentin confirmed the mesenchymal origin of cells and tracked morphological changes during differentiation. The expression patterns of S100β and glial fibrillary acidic protein (GFAP), were used as indicator for neural differentiation. Results suggested that this process was enhanced when the cells were seeded on the AuNRs compared to the tissue-culture surface. The present study indicates that the design and the surface properties of the AuNRs enhances neural differentiation of hMSCs and hence, would be beneficial for neural tissue engineering scaffolds
The complex Y-chromosomal history of gorillas
Studies of the evolutionary relationships among gorilla populations using autosomal and mitochondrial sequences suggest that male-mediated gene flow may have been important in the past, but data on the Y-chromosomal relationships among the gorilla subspecies are limited. Here, we genotyped blood and noninvasively collected fecal samples from 12 captives and 257 wild male gorillas of known origin representing all four subspecies (Gorilla gorilla gorilla, G. g. diehli, G. beringei beringei, and G. b. graueri) at 10 Y-linked microsatellite loci resulting in 102 unique Y-haplotypes for 224 individuals. We found that western lowland gorilla (G. g. gorilla) haplotypes were consistently more diverse than any other subspecies for all measures of diversity and comprised several genetically distinct groups. However, these did not correspond to geographical proximity and some closely related haplotypes were found several hundred kilometers apart. Similarly, our broad sampling of eastern gorillas revealed that mountain (G. b. beringei) and Grauer's (G. b. graueri) gorilla Y-chromosomal haplotypes did not form distinct clusters. These observations suggest structure in the ancestral population with subsequent mixing of differentiated haplotypes by male dispersal for western lowland gorillas, and postisolation migration or incomplete lineage sorting due to short divergence times for eastern gorillas
Habitable Zones in the Universe
Habitability varies dramatically with location and time in the universe. This
was recognized centuries ago, but it was only in the last few decades that
astronomers began to systematize the study of habitability. The introduction of
the concept of the habitable zone was key to progress in this area. The
habitable zone concept was first applied to the space around a star, now called
the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable
zones have been proposed. We review the historical development of the concept
of habitable zones and the present state of the research. We also suggest ways
to make progress on each of the habitable zones and to unify them into a single
concept encompassing the entire universe.Comment: 71 pages, 3 figures, 1 table; to be published in Origins of Life and
Evolution of Biospheres; table slightly revise
Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI Direct study
Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D.
Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n=403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n=458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariate regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models.
Findings: A higher Tpred was associated with healthier diets high in wholegrain (β=0.004 g, p=0.02 and β=0.003 g, p=0.03) and lower energy intake (β=-0.0002 kcal, p=0.04 and β=-0.0002 kcal, p=0.003), and saturated fat (β=-0.03 g, p<.0001 and β=-0.03 g, p<.0001), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and improved lipid profiles HDL-cholesterol (β=0.07 mmol/L, p<.0001), (β=0.08 mmol/L, p=0.0002), and triglycerides (β=-0.1 mmol/L, p=0.003), (β=-0.2 mmol/L, p=0.0002), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat content (β=-0.74 %, p<.0001), and lower fasting concentrations of HbA1c (β=-0.9mmol/mol, p=0.02), glucose (β=-0.2 mmol/L, p=0.01) and insulin (β=-11.0 pmol/mol, p=0.01). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, p=0.03) and insulin (β=-9.2 pmol/mol, p=0.04) concentrations in cohort 2.
Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health
Predicting and elucidating the etiology of fatty liver disease : A machine learning modeling and validation study in the IMI DIRECT cohorts
Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Methods and findings We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n= 795) or at high risk of developing the disease (n= 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (= 5%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86;p = 5%) rather than a continuous one. Conclusions In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see:) and made it available to the community.Peer reviewe
The 2001 Superoutburst of WZ Sagittae
We report the results of a worldwide campaign to observe WZ Sagittae during
its 2001 superoutburst. After a 23-year slumber at V=15.5, the star rose within
2 days to a peak brightness of 8.2, and showed a main eruption lasting 25 days.
The return to quiescence was punctuated by 12 small eruptions, of ~1 mag
amplitude and 2 day recurrence time; these "echo outbursts" are of uncertain
origin, but somewhat resemble the normal outbursts of dwarf novae. After 52
days, the star began a slow decline to quiescence.
Periodic waves in the light curve closely followed the pattern seen in the
1978 superoutburst: a strong orbital signal dominated the first 12 days,
followed by a powerful /common superhump/ at 0.05721(5) d, 0.92(8)% longer than
P_orb. The latter endured for at least 90 days, although probably mutating into
a "late" superhump with a slightly longer mean period [0.05736(5) d]. The
superhump appeared to follow familiar rules for such phenomena in dwarf novae,
with components given by linear combinations of two basic frequencies: the
orbital frequency omega_o and an unseen low frequency Omega, believed to
represent the accretion disk's apsidal precession. Long time series reveal an
intricate fine structure, with ~20 incommensurate frequencies. Essentially all
components occurred at a frequency n(omega_o)-m(Omega), with m=1, ..., n. But
during its first week, the common superhump showed primary components at n
(omega_o)-Omega, for n=1, 2, 3, 4, 5, 6, 7, 8, 9 (i.e., m=1 consistently); a
month later, the dominant power shifted to components with m=n-1. This may
arise from a shift in the disk's spiral-arm pattern, likely to be the
underlying cause of superhumps.
The great majority of frequency components ... . (etc., abstract continues)Comment: PDF, 54 pages, 4 tables, 21 figures, 1 appendix; accepted, in press,
to appear July 2002, PASP; more info at http://cba.phys.columbia.edu
Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015
This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates
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