Optical and near-IR observations of SN 1998bw

SN 1998bw, especially after the discovery of GRB 030329/SN 2003dh, seems to be the equivalent of the Rosetta stone for the SN/GRB connection. In this paper I review optical and near IR observations that have been carried out for this uncanny object, which has probably confirmed suspicions and ideas originally formulated in the early seventies of last century.Comment: 9 pages, 7 figures. Invited review to the IAU Colloquium n. 192, SUPERNOVAE: ten years of SN 1993J, Valencia (Spain

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function

BACKGROUND: Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates. OBJECTIVE: To characterise genetic and clinical findings in patients with SIX3 mutations. METHODS: Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish. RESULTS: In a cohort of patients (n = 800) with HPE, SIX3 mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in SIX3 result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of SIX3 mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%. CONCLUSIONS: Our data suggest that SIX3 mutations result in relatively severe HPE and that there is a genotype-phenotype correlation, as shown by functional studies using animal models

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Extension of the optimised virtual fields method to estimate viscoelastic material parameters from 3D dynamic displacement fields

In vivo measurement of the mechanical properties of soft tissues is essential to provide necessary data in biomechanics and medicine (early cancer diagnosis, study of traumatic brain injuries, etc.). Imaging techniques such as magnetic resonance elastography can provide 3D displacement maps in the bulk and in vivo, from which, using inverse methods, it is then possible to identify some mechanical parameters of the tissues (stiffness, damping, etc.). The main difficulties in these inverse identification procedures consist in dealing with the pressure waves contained in the data and with the experimental noise perturbing the spatial derivatives required during the processing. The optimised virtual fields method (OVFM) (Comput. Mech. 34, 2004, 439), designed to be robust to noise, presents natural and rigorous solution to deal with these problems. The OVFM has been adapted to identify material parameter maps from magnetic resonance elastography data consisting of 3D displacement fields in harmonically loaded soft materials. In this work, the method has been developed to identify elastic and viscoelastic models.The OVFM sensitivity to spatial resolution and to noise has been studied by analysing 3D analytically simulated displacement data. This study evaluates and describes the OVFM identification performances: Different biases on the identified parameters are induced by the spatial resolution and experimental noise. The well-known identification problems in the case of quasi-incompressible materials also find a natural solution in the OVFM. Moreover, an a posteriori criterion to estimate the local identification quality is proposed. The identification results obtained on actual experiments are briefly presente

Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort

Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). However, the possible relationship between CMV infection and leukocyte TL and TA has not been well-examined in vivo. This study examined the associations of CMV seropositivity and CMV IgG antibodies with leukocyte (TL) and (TA) in a sample of 434 healthy individuals (ages 53-76) from the Whitehall II cohort. Positive CMV serostatus was significantly associated with lower TA among women, and higher CMV IgG antibody levels were associated with lower TA in the overall sample. However, neither CMV seropositivity nor CMV IgG antibody levels (reflecting subclinical reactivation) among the seropositive were significantly associated with TL. These associations were robust to adjustment for age, employment grade, BMI, and smoking status. The results demonstrate that CMV seropositivity and subclinical reactivation predict lower TA. Future longitudinal studies should test whether the association of CMV with lower TA contributes to accelerated telomere shortening over time