The number of long gamma-ray bursts (GRBs) known to have occurred in the distant Universe (z greater than 5) is small (approx 15), however these events provide a powerful way of probing star ...formation at the onset of galaxy evolution. In this paper, we present the case for GRB100205A being a largely overlooked high-redshift event. While initially noted as a high-z candidate, this event and its host galaxy have not been explored in detail. By combining optical and near-infrared Gemini afterglow imaging (at t less than 1.3 days since burst) with deep late-time limits on host emission from the Hubble Space Telescope, we show that the most likely scenario is that GRB100205A arose in the redshift range 4-8. GRB100205A is an example of a burst whose afterglow, even at 1 hour post-burst, could only be identified by 8m class IR observations, and suggests that such observations of all optically dark bursts may be necessary to significantly enhance the number of high-redshift GRBs known.
In humans, vitamin B-12 (cobalamin) transport involves 3 paralogous proteins: transcobalamin, haptocorrin, and intrinsic factor. Zebrafish (Danio rerio) express 3 genes that encode proteins ...homologous to known B-12 carrier proteins: tcn2 (a transcobalamin ortholog) and 2 atypical β-domain-only homologs, tcnba and tcnbb.
Given the orthologous relation between zebrafish Tcn2 and human transcobalamin, we hypothesized that zebrafish carrying null mutations of tcn2 would exhibit phenotypes consistent with vitamin B-12 deficiency.
First-generation and second-generation tcn2–/– zebrafish were characterized using phenotypic assessments, metabolic analyses, viability studies, and transcriptomics.
Homozygous tcn2–/– fish produced from a heterozygous cross are viable and fertile but exhibit reduced growth, which persists into adulthood. When first-generation female tcn2–/– fish are bred, their offspring exhibit gross developmental and metabolic defects. These phenotypes are observed in all offspring from a tcn2–/– female regardless of the genotype of the male mating partner, suggesting a maternal effect, and can be rescued with vitamin B-12 supplementation. Transcriptome analyses indicate that offspring from a tcn2–/– female exhibit expression profiles distinct from those of offspring from a tcn2+/+ female, which demonstrate dysregulation of visual perception, fatty acid metabolism, and neurotransmitter signaling pathways.
Our findings suggest that the deposition of vitamin B-12 in the yolk by tcn2–/– females may be insufficient to support the early development of their offspring. These data present a compelling model to study the effects of vitamin B-12 deficiency on early development, with a particular emphasis on transgenerational effects and gene–environment interactions.
Lipodystrophy is a major side-effect of antiretroviral therapy but its pathophysiology remains elusive. In-vitro studies show that HIV-1-protease inhibitors affect adipocyte differentiation at an ...early step involving sterol-regulatory-element-binding-protein-1 (SREBP1), but in-vivo studies are lacking.
We compared fat morphology and mRNA and protein expression of major adipocyte differentiation markers and cytokines in subcutaneous abdominal adipose tissue from 26 HIV-1-infected patients who developed peripheral lipoatrophy while on protease inhibitors and from 18 HIV-1-seronegative healthy controls.
Patients' fat contained a higher proportion of small adipocytes than control fat, together with lower mRNA concentrations of the adipogenic differentiation factors CCAAT-enhancer binding protein (C/EBP) β and α, peroxisome proliferator-activated receptor (PPAR) γ, and the 1c isoform of SREBP1, with a median decrease of 93% in the latter. The SREBP1 protein concentration was increased 2·6-fold, whereas the PPARγ protein concentration was decreased by 70%. The expression of adipocyte-specific markers, including leptin, was lower in fat from patients than in fat from controls, whereas expression of tumour necrosis factor (TNF) α was higher and correlated negatively with the expression of SREBP1c and downstream adipogenic factors. SREBP1c mRNA concentrations correlated negatively, and TNFα mRNA concentrations positively, with glycaemia and insulin resistance, but did not correlate with lipid variables.
The altered differentiation status of peripheral adipocytes in HIV-1-infected patients with antiretroviral-induced lipoatrophy is associated with greatly reduced SREBP1c expression. Since the differentiation factor SREBP1 is rapidly targeted by protease inhibitors in vitro, our results suggest that SREBP1c could be an important mediator of peripheral lipoatrophy in this setting, leading to metabolic alterations such as insulin resistance.
We report on observations of GRB 080503, a short gamma-ray burst (GRB) with very bright extended emission (about 30 times the gamma-ray fluence of the initial spike) in conjunction with a thorough ...comparison to other short Swift events. In spite of the prompt-emission brightness, however, the optical counterpart is extraordinarily faint, never exceeding 25 mag in deep observations starting at {approx}1 hr after the Burst Alert Telescope (BAT) trigger. The optical brightness peaks at {approx}1 day and then falls sharply in a manner similar to the predictions of Li and Paczynski (1998) for supernova-like emission following compact binary mergers. However, a shallow spectral index and similar evolution in X-rays inferred from Chandra observations are more consistent with an afterglow interpretation. The extreme faintness of this probable afterglow relative to the bright gamma-ray emission argues for a very low density medium surrounding the burst (a 'naked' GRB), consistent with the lack of a coincident host galaxy down to 28.5 mag in deep Hubble Space Telescope imaging. The late optical and X-ray peak could be explained by a slightly off-axis jet or by a refreshed shock. Our observations reinforce the notion that short GRBs generally occur outside regions of active star formation, but demonstrate that in some cases the luminosity of the extended prompt emission can greatly exceed that of the short spike, which may constrain theoretical interpretation of this class of events. This extended emission is not the onset of an afterglow, and its relative brightness is probably either a viewing-angle effect or intrinsic to the central engine itself. Because most previous BAT short bursts without observed extended emission are too faint for this signature to have been detectable even if it were present at typical level, conclusions based solely on the observed presence or absence of extended emission in the existing Swift sample are premature.
We present observations of the optical afterglow of GRB\,170817A, made by the {\it Hubble Space Telescope}, between February and August 2018, up to one year after the neutron star merger, GW170817. ...The afterglow shows a rapid decline beyond \(170\)~days, and confirms the jet origin for the observed outflow, in contrast to more slowly declining expectations for `failed-jet' scenarios. We show here that the broadband (radio, optical, X-ray) afterglow is consistent with a structured outflow where an ultra-relativistic jet, with Lorentz factor \(\Gamma\gtrsim100\), forms a narrow core (\(\sim5^\circ\)) and is surrounded by a wider angular component that extends to \(\sim15^\circ\), which is itself relativistic (\(\Gamma\gtrsim5\)). For a two-component model of this structure, the late-time optical decline, where \(F \propto t^{-\alpha}\), is \(\alpha=2.20\pm0.18\), and for a Gaussian structure the decline is \(\alpha=2.45\pm0.23\). We find the Gaussian model to be consistent with both the early \(\sim10\) days and late \(\gtrsim290\) days data. The agreement of the optical light curve with the evolution of the broadband spectral energy distribution and its continued decline indicates that the optical flux is arising primarily from the afterglow and not any underlying host system. This provides the deepest limits on any host stellar cluster, with a luminosity \(\lesssim 4000 L_\odot~(M_{\rm F606W}\gtrsim-4.3)\).
In patients with pelvic venous disorders secondary to pelvic venous insufficiency (PVI), the optimal imaging modality is ill-defined. Transabdominal ultrasound (TAU) is widely used to identify the ...presence of iliac vein stenosis. The purpose of the present investigation is to determine the accuracy of TAU for determining the presence of an iliac vein area-reducing lesion compared with intravascular ultrasound (IVUS).
From January to December 2020, a retrospective review of prospectively collected data from 96 patients treated for symptomatic PVI at the Center for Vascular Medicine was performed. All patients had complete history and physical examination findings, demographics, CEAP (clinical, etiologic, anatomic, pathophysiologic), revised venous clinical severity score, and TAU, diagnostic venography, and IVUS measurements recorded in our electronic medical record system. All TAU measurements were performed by the same ultrasound technician with the patient in the supine position. Iliac vein diameters of the common femoral, external iliac, and common iliac veins and the inferior vena cava were obtained. Differences in body habitus were normalized by dividing the minimum diameter measurement of the stenotic vessel with that of the ipsilateral common femoral vein, subtracting this number from 1 and multiplying by 100 (stenosis = 1 − minimal diameter/common femoral diameter × 100). The normalized stenoses were then compared with the IVUS-derived area reducing measurements. A receiver operating characteristic curve was created, and logistic regression analysis for the probability of predicting an area-reducing lesion of >50% and >60% with TAU was performed. The sensitivity, specificity, and positive and negative predictive values were calculated.
The average age of the entire cohort was 49.8 ± 13.5 years, with 69 women and 27 men. The CEAP distribution was as follows: C0, 5%; C1, 5%; C2, 10%; C3, 40%; C4a,b, 30%; C5, 7%; and C6, 3%. The average revised venous clinical severity score was 6.2 ± 2.6. The indications for intervention were leg symptoms alone in 43%, pelvic symptoms alone in 3%, and combined leg and pelvic symptoms in 54%. TAU identified a stenosis of ≥50% in 92 of the 96 patients (96%). For a ≥50% stenosis, a normalized diameter of ≤3 mm demonstrated a sensitivity, specificity, and positive and negative predictive value of 75%, 75%, 98%, and 12%, respectively. Logistic regression analysis indicated that TAU was significant in predicting the presence of a ≥60% area-reducing lesion (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .009). The area under the receiver operating characteristic curve (c-statistic) was 68.6%. The sensitivity, specificity, and positive and negative predictive values were 66.7%, 66.7%, 81.5%, and 47.6%, respectively, for a normalized diameter of ≥4 mm.
The ability of TAU to identify an iliac vein stenosis of ≥50% is 96%. The positive predictive value for TAU to identify a ≥60% iliac vein area-reducing lesion is high, with moderate sensitivity and specificity. For patients with symptoms consistent with pelvic venous disorders secondary to PVI, TAU is a good preintervention screening modality for properly trained vascular imaging specialists with findings that correlate well with IVUS measurements.
ObjectiveTo investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to ...SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.DesignA prospective observational study.SettingPublic healthcare system in Santa Clara County (California, USA).ParticipantsWomen with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021.OutcomesSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.ResultsOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60–180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1–4, 5–12, and 13–28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection.ConclusionsMaternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.
The binary neutron star merger GW170817 was the first multi-messenger event observed in both gravitational and electromagnetic waves. The electromagnetic signal began approximately 2 seconds ...post-merger with a weak, short burst of gamma-rays, which was followed over the next hours and days by the ultraviolet, optical and near-infrared emission from a radioactively- powered kilonova. Later, non-thermal rising X-ray and radio emission was observed. The low luminosity of the gamma-rays and the rising non-thermal flux from the source at late times could indicate that we are outside the opening angle of the beamed relativistic jet. Alternatively, the emission could be arising from a cocoon of material formed from the interaction between a jet and the merger ejecta. Here we present late-time optical detections and deep near-infrared limits on the emission from GW170817 at 110 days post-merger. Our new observations are at odds with expectations of late-time emission from kilonova models, being too bright and blue. Instead, the emission arises from the interaction between the relativistic ejecta of GW170817 and the interstellar medium. We show that this emission matches the expectations of a Gaussian structured relativistic jet, which would have launched a high luminosity short GRB to an aligned observer. However, other jet structure or cocoon models can also match current data - the future evolution of the afterglow will directly distinguish the origin of the emission.
Context . Gamma-ray bursts (GRBs) are ideal probes of the Universe at high redshift (ɀ), pinpointing the locations of the earliest star-forming galaxies and providing bright backlights with simple ...featureless power-law spectra that can be used to spectrally fingerprint the intergalactic medium and host galaxy during the period of reionization. Future missions such as Gamow Explorer (hereafter Gamow) are being proposed to unlock this potential by increasing the rate of identification of high-ɀ (ɀ > 5) GRBs in order to rapidly trigger observations from 6 to 10 m ground telescopes, the James Webb Space Telescope (JWST), and the upcoming Extremely Large Telescopes (ELTs). Aims . Gamow was proposed to the NASA 2021 Medium-Class Explorer (MIDEX) program as a fast-slewing satellite featuring a wide-field lobster-eye X-ray telescope (LEXT) to detect and localize GRBs with arcminute accuracy, and a narrow-field multi-channel photo-ɀ infrared telescope (PIRT) to measure their photometric redshifts for > 80% of the LEXT detections using the Lyman- α dropout technique. We use a large sample of observed GRB afterglows to derive the PIRT sensitivity requirement. Methods . We compiled a complete sample of GRB optical–near-infrared (optical-NIR) afterglows from 2008 to 2021, adding a total of 66 new afterglows to our earlier sample, including all known high-ɀ GRB afterglows. This sample is expanded with over 2837 unpublished data points for 40 of these GRBs. We performed full light-curve and spectral-energy-distribution analyses of these after-glows to derive their true luminosity at very early times. We compared the high-ɀ sample to the comparison sample at lower redshifts. For all the light curves, where possible, we determined the brightness at the time of the initial finding chart of Gamow, at different high redshifts and in different NIR bands. This was validated using a theoretical approach to predicting the afterglow brightness. We then followed the evolution of the luminosity to predict requirements for ground- and space-based follow-up. Finally, we discuss the potential biases between known GRB afterglow samples and those to be detected by Gamow. Results . We find that the luminosity distribution of high-ɀ GRB afterglows is comparable to those at lower redshift, and we therefore are able to use the afterglows of lower-ɀ GRBs as proxies for those at high ɀ. We find that a PIRT sensitivity of 15 µJy (21 mag AB) in a 500 s exposure simultaneously in five NIR bands within 1000 s of the GRB trigger will meet the Gamow mission requirements. Depending on the ɀ and NIR band, we find that between 75% and 85% of all afterglows at ɀ > 5 will be recovered by Gamow at 5 σ detection significance, allowing the determination of a robust photo-ɀ. As a check for possible observational biases and selection effects, we compared the results with those obtained through population-synthesis models, and find them to be consistent. Conclusions . Gamow and other high-ɀ GRB missions will be capable of using a relatively modest 0.3 m onboard NIR photo-ɀ telescope to rapidly identify and report high-ɀ GRBs for further follow-up by larger facilities, opening a new window onto the era of reionization and the high-redshift Universe.
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