ABSTRACT We present the results of a deep imaging survey of the Virgo cluster of galaxies, concentrated around the cores of Virgo subclusters A and B. The goal of this survey was to detect and study ...very low surface brightness features present in Virgo, including discrete tidal features, the faint halos of luminous galaxies, and the diffuse intracluster light (ICL). Our observations span roughly 16 degrees2 in two filters, reaching a 3 limiting depth of = 29.5 and = 28.5 mag arcsec−2. At these depths, our limiting systematic uncertainties are astrophysical: variations in faint background sources as well as scattered light from galactic dust. We show that this dust-scattered light is well traced by deep far-infrared imaging, making it possible to separate it from true diffuse light in Virgo. We use our imaging to trace and measure the color of the diffuse tidal streams and ICL in the Virgo core near M87, in fields adjacent to the core including the M86/M84 region, and to the south of the core around M49 and subcluster B, along with the more distant W cloud around NGC 4365. Overall, the bulk of the projected ICL is found in the Virgo core and within the W cloud; we find little evidence for an extensive ICL component in the field around M49. The bulk of the ICL we detect is fairly red in color (B − V = 0.7-0.9), indicative of old, evolved stellar populations. Based on the luminosity of the observed ICL features in the cluster, we estimate a total Virgo ICL fraction of 7%-15%. This value is somewhat smaller than that expected for massive, evolved clusters, suggesting that Virgo is still in the process of growing its extended ICL component. We also trace the shape of M87's extremely boxy outer halo out to ∼150 kpc, and show that the current tidal stripping rate from low luminosity galaxies is insufficient to have built M87's outer halo over a Hubble time. We identify a number of previously unknown low surface brightness structures around galaxies projected close to M86 and M84. The extensive diffuse light seen in the infalling W cloud around NGC 4365 is likely to be subsumed in the general Virgo ICL component once the group enters the cluster, illustrating the importance of group infall in generating ICL. Finally, we also identify another large and extremely low surface brightness ultradiffuse galaxy, likely in the process of being shredded by the cluster tidal field. With the survey complete, the full imaging data set is now available for public release.
Innate immune responses rely on rapid and precise gene regulation mediated by accessibility of regulatory regions to transcription factors (TFs). In natural killer (NK) cells and other innate ...lymphoid cells, competent enhancers are primed during lineage acquisition, and formation of de novo enhancers characterizes the acquisition of innate memory in activated NK cells and macrophages. Here, we investigated how primed and de novo enhancers coordinate to facilitate high-magnitude gene induction during acute activation. Epigenomic and transcriptomic analyses of regions near highly induced genes (HIGs) in NK cells both in vitro and in a model of Toxoplasma gondii infection revealed de novo chromatin accessibility and enhancer remodeling controlled by signal-regulated TFs STATs. Acute NK cell activation redeployed the lineage-determining TF T-bet to de novo enhancers, independent of DNA-sequence-specific motif recognition. Thus, acute stimulation reshapes enhancer function through the combinatorial usage and repurposing of both lineage-determining and signal-regulated TFs to ensure an effective response.
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•Inducible high-density p300 enhancers form in proximity to highly dynamic genes•Strong transcriptional induction occurs with both primed and non-primed enhancers•De novo enhancers form in vivo during NK cell response to Toxoplasma gondii infection•STATs initiate chromatin opening with T-bet redeployment to non-canonical sites
During development, innate lymphocytes acquire defined sets of primed enhancers facilitating the rapid immune response. In this issue of Immunity, Sciumè et al. delineate the epigenetic changes occurring during acute NK cell activation, revealing the formation of de novo enhancers and repurposing of both lineage-determining and signal-regulated transcription factors.
Objective The aim of the Prospective Observational Trial to Optimize Pediatric Health in IUGR Study was to evaluate the optimal management of fetuses with an estimated fetal weight less than the 10th ...centile. The objective of this secondary analysis was to describe the role of the cerebroplacental ratio (CPR) in the prediction of adverse perinatal outcome. Study Design More than 1100 consecutive singleton pregnancies with intrauterine growth restriction (IUGR) were recruited over 2 years at 7 centers, undergoing serial sonographic evaluation including multivessel Doppler measurement. CPR was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Results Data for CPR calculation was available in 881 cases, which was performed at a mean gestational age of 33 weeks (interquarile range, 28.7–35.9). Of the 146 cases with CPR less than 1, 18% (n = 27) had an adverse perinatal outcome. This conferred an 11-fold increased risk (odds ratio, 11.7; P < .0001) when compared with cases with normal CPR (2%; 14 of 735). An abnormal CPR was present in all 3 cases of mortality. Prediction of adverse outcomes was comparable when using all definitions of abnormal CPR. Conclusion Irrespective of the CPR calculation used, brain sparing is significantly associated with an adverse perinatal outcome in IUGR. This adds further weight to integrating CPR evaluation into the clinical assessment of IUGR pregnancies. The impact of this finding on long-term neurodevelopmental outcomes in this patient cohort is underway.
Not simply an attribute of the adaptive immune system, immunological memory can be viewed on multiple levels. Accordingly, the molecular basis of memory comprises multiple mechanisms. The advent of ...new sequencing technologies has greatly enhanced the understanding of gene regulation and lymphocyte specification, and improved measurement of chromatin states affords new insights into the epigenomic and transcriptomic programs that underlie memory. Beyond canonical genes, the involvement of long noncoding RNAs (lncRNAs) is becoming increasingly apparent, and it appears that there are more than two to three times as many lncRNAs as protein-coding genes. lncRNAs can directly interact with DNA, RNA, and proteins, and a single lncRNA can contain multiple modular domains and thus interact with different classes of molecules. Yet, most lncRNAs have not been tested for function, and even fewer knockout mice have been generated. It is therefore timely to consider new potential mechanisms that may contribute to immune memory.
Preterm delivery Slattery, Michael M; Morrison, John J
The Lancet (British edition),
11/2002, Letnik:
360, Številka:
9344
Journal Article
Recenzirano
Preterm delivery and its short-term and long-term sequelae constitute a serious problem in terms of mortality, disability, and cost to society. The incidence of preterm delivery, which has increased ...in recent years, is associated with various epidemiological and clinical risk factors. Results of randomised controlled trials suggest that attempts to reduce these risk factors by use of drugs are limited by side-effects and poor efficacy. An improved understanding of the physiological pathways that regulate uterine contraction and relaxation in animals and people has, however, helped to define the complex processes that underlie parturition (term and preterm), and has led to new scientific approaches for myometrial modulation. The continuing elucidation of the mechanisms that regulate preterm labour, combined with rigorous clinical assessment, offer hope for future solutions.
Concentrations of 10 perfluoroalkyl substances (PFASs) were measured in 16 pools of human milk from Ireland. Only four PFASs were detected (PFOA, PFNA, PFHxS and PFOS), with concentrations dominated ...by PFOA which was detected in all samples at a median of 0.10 ng/mL. Concentrations and the relative abundance of PFASs in human milk from Ireland are within the range reported for other countries. Estimated exposures for nursing infants to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) do not suggest a health concern. A one compartment pharmacokinetic model was used to predict the intakes of PFOS and PFOA required to support the observed concentrations in human milk. This suggests current adult exposure in Ireland to PFOS is below the provisional tolerable weekly intake (TWI) proposed by EFSA. In contrast, the model predicts that the maximum concentration detected in human milk in this study, implies a level of adult exposure that would exceed EFSA’s provisional TWI for PFOA. As exposure of the Irish population to PFASs via drinking water, indoor air and dust is well-characterised, current understanding suggests that the major contributor to overall exposure of the Irish population is via the diet and/or less well-studied pathways like dermal uptake from PFAS-containing fabrics and cosmetics.
•PFOA, PFOS, PFNA, and PFHxS detected in Irish human milk.•Concentrations within the range of studies elsewhere.•Exposures of nursing infants to PFOS and PFOA not of health concern.•Modelled adult intakes of PFOA in some instances exceed provisional EFSA TWI.•Measurement of Irish exposure via the diet and dermal uptake recommended.
We use deep V-band surface photometry of five of the brightest elliptical galaxies in the Virgo Cluster to search for diffuse tidal streams, shells, and plumes in their outer halos (r>50 kpc). We fit ...and subtract elliptical isophotal models from the galaxy images to reveal a variety of substructure, with surface brightnesses in the range {mu} {sub V} = 26-29 mag arcsec{sup -2}. M49 possesses an extended, interleaved shell system reminiscent of the radial accretion of a satellite companion, while M89's complex system of shells and plumes suggests a more complicated accretion history involving either multiple events or a major merger. M87 has a set of long streamers as might be expected from stripping of low luminosity dwarfs on radial orbits in Virgo. M86 also displays a number of small streams indicative of stripping of dwarf companions, but these comprise much less luminosity than those of M87. Only M84 lacks significant tidal features. We quantify the photometric properties of these structures, and discuss their origins in the context of each galaxy's environment and kinematics within the Virgo Cluster.
Objective The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. Study Design We performed a multicenter, prospective trial ...of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. Results Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal ( P = .0068) and velamentous ( P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3–9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1–14.3). Conclusion Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies.
Intrauterine growth restriction (IUGR) is the single largest contributing factor to perinatal mortality in non-anomalous fetuses. Advances in antenatal and neonatal critical care have resulted in a ...reduction in neonatal deaths over the past decades, while stillbirth rates have remained unchanged. Antenatal detection rates of fetal growth failure are low, and these pregnancies carry a high risk of perinatal death.
The Prospective Observational Trial to Optimize Paediatric Health in IUGR (PORTO) Study recruited 1,200 ultrasound-dated singleton IUGR pregnancies, defined as EFW <10th centile, between 24+0 and 36+6 weeks gestation. All recruited fetuses underwent serial sonographic assessment of fetal weight and multi-vessel Doppler studies until birth. Perinatal outcomes were recorded for all pregnancies. Case records of the perinatal deaths from this prospectively recruited IUGR cohort were reviewed, their pregnancy details and outcome were analysed descriptively and compared to the entire cohort.
Of 1,116 non-anomalous singleton infants with EFW <10th centile, 6 resulted in perinatal deaths including 3 stillbirths and 3 early neonatal deaths. Perinatal deaths occurred between 24+6 and 35+0 weeks gestation corresponding to birthweights ranging from 460 to 2260 grams. Perinatal deaths occurred more commonly in pregnancies with severe growth restriction (EFW <3rd centile) and associated abnormal Doppler findings resulting in earlier gestational ages at delivery and lower birthweights. All of the described pregnancies were complicated by either significant maternal comorbidities, e.g. hypertension, systemic lupus erythematosus (SLE) or diabetes, or poor obstetric histories, e.g. prior perinatal death, mid-trimester or recurrent pregnancy loss. Five of the 6 mortalities occurred in women of non-Irish ethnic backgrounds. All perinatal deaths showed abnormalities on placental histopathological evaluation.
The PNMR in this cohort of prenatally identified IUGR cases was 5.4/1,000 and compares favourably to the overall national rate of 4.1/1,000 births, which can be attributed to increased surveillance and timely delivery. Despite antenatal recognition of IUGR and associated maternal risk factors, not all perinatal deaths can be prevented.
Approximately 3% of pregnancies are diagnosed with a fetal anomaly, of which a proportion is fatal or life-limiting. The introduction of legislation for termination of pregnancy (TOP) in Ireland in ...2019 for conditions ‘likely to lead to the death of the fetus’, made TOP for ‘fatal fetal anomaly’ (FFA) an option for pregnant women in Ireland.
This study examined all cases of TOP performed for major fetal anomaly over the first 3-years of service implementation, including those cases that did not meet the legal criteria resulting in women traveling outside Ireland for abortion care.
A retrospective service evaluation of tertiary fetal medicine clinics in 2 tertiary maternity hospitals between 2019-2021 was undertaken. We compared pregnancies diagnosed with FFA who underwent TOP in Ireland and pregnancies that did not meet the legal criteria, and hence women traveled outside Ireland for TOP.
Overall, 139 pregnancies met the inclusion criteria. Eighty-three (59.7%) cases had TOP in the tertiary maternity hospital (local), and 56 (40.3%) traveled abroad, mainly to the UK. Demographic characteristics were similar between the two groups, as was gestation at diagnosis and delivery. All cases where TOP was local were discussed at fetal medicine multidisciplinary meetings, compared to 34% of cases that ultimately traveled outside Ireland for TOP. The most common indication (25/83;30.1%) for local TOP was Trisomy 18, followed by anencephaly. Traveling to get abortion care was mainly because of the diagnosis of Trisomy 21 (30/56;53.6%), followed by other multiple structural anomalies/syndromes deemed locally as not meeting the legal criteria.
Legislation for TOP for fetal anomaly, restricted to fatal diagnoses, is difficult to implement, requires significant multidisciplinary input, and can lead to limited services for pregnancies diagnosed with major fetal anomalies. Our findings emphasise the impact of legislative barriers to abortion care for fetal anomaly and the need for policies and services that support women's access to TOP for fetal anomaly.
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