TiME - The Titan Mare Explorer Stofan, Ellen; Lorenz, R.; Lunine, J. ...
2013 IEEE Aerospace Conference,
2013-March
Conference Proceeding
The Titan Mare Explorer (TiME) is a Discovery-class mission concept that underwent a detailed Phase A study in 2011-2012. The mission would splashdown a capsule on Titan's ethane sea Ligeia Mare as ...early as the summer of 2023, and would spend multiple Titan days performing science measurements and transmitting data directly back to Earth. This paper reviews briefly the mission concept.
Mutations in the methyl-CpG-binding protein gene MECP2 at Xq28 cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by a period of stagnation followed by ...regression in the development of young girls. Mutations were sought in MECP2 in 48 females with classical sporadic RTT, seven families with possible familial RTT and five sporadic females with features suggestive, but not diagnostic of RTT. Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases. Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT. Twenty-one different mutations were identified (12 missense, four nonsense and five frame-shift mutations); 14 of these were novel. All missense mutations were located either in the methyl-CpG-binding domain or in the transcription repression domain. Nine recurrent mutations were characterized in a total of 33 unrelated cases (73% of all cases with MECP2 mutations). Significantly milder disease was noted in patients carrying missense mutations as compared with those with truncating mutations ( P = 0. 0023), and milder disease was associated with late as compared with early truncating mutations ( P = 0.0190).
Background and aims: Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, clinical penetrance varies and other genes may modify ...disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n = 56) and C282Y homozygous haemochromatosis patients presenting clinically (n = 60). Methods: All participating relatives had a structured interview, clinical assessment, and laboratory investigations. Health related quality of life was measured (SF-36 version 2). Results: In total, 92% of 180 eligible first degree relatives were interviewed in the “screened” family group and 85% of 143 eligible relatives in the “patient” group. Of 59 relatives homozygous for C282Y, 76% of men and 32% of women had the “iron phenotype” (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by lifestyle factors, and 6% by being male. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the “screened” and “patient” groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. Conclusions:HFE C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. Lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes.
Objective: To determine the prevalence and causation of late onset cerebellar ataxia (LOCA) in south east Wales, United Kingdom. Methods: A population based study of LOCA was conducted in a defined ...geographical region with a total population of 742 400. Multiple sources of ascertainment were used to identify all cases prevalent on 1 January 2001. The inclusion criteria were: a predominantly progressive cerebellar ataxia with onset of symptoms at age ⩾18 years; and disease duration of ⩾1 year. Cases with known acquired ataxias, ataxic syndromes with associated prominent autonomic dysfunction and/or atypical parkinsonism suggestive of multiple system atrophy and disorders with ataxia as a minor feature were excluded. Results: We identified 76 index cases of LOCA, of whom 63 were sporadic, idiopathic LOCA (ILOCA) and 13 were familial LOCA, of whom six had either spinocerebellar ataxia type 6, Friedreich’s ataxia or dominant episodic ataxia. The mean annual incidence rate for the period 1999–2001 was 0.3/100 000 population/year. The crude prevalence rates were 8.4 per 100 000 (95% CI 7.2 to 11.6) for ILOCA and 1.8 per 100 000 (95% CI 0.8 to 2.7) for inherited LOCA. Of the 54/63 (85.7%) patients with ILOCA who were assessed, mean (SD) age at onset of symptoms was 53.8 (14.1) years (range 19 to 78) with a male:female ratio of 2.1:1. The mean disease duration was 8.7 (6.3) years (range 1 to 31). The most frequent presenting complaint was disturbance in gait (90.7%). One-third had a relatively pure cerebellar syndrome (33.3%) and two-thirds (66.7%) had additional extracerebellar neurological features. The majority (92%) were ambulant but only 9.3% were independently self-caring. Conclusion: This population based study provides insight into LOCA within a defined region and will inform decisions about the rational use of healthcare resources for patients with LOCA.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to ...chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.
Zhang J, Bao X, Cao G, Jiang S, Zhu X, Lu H, Jia L, Pan H, Fehr S, Davis M, Leonard H, Ravine D, Wu X. What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in ...Rett syndrome?
The MECP2 mutations occurring in the severe neurological disorder Rett syndrome are predominantly de novo, with rare familial cases. The aims of this study were to provide a precise estimate of the parental origin of MECP2 mutations using a large Chinese sample and to assess whether parental origin varied by mutation type. The parental origin was paternal in 84/88 95.5%, (95% confidence interval 88.77–98.75) of sporadic Chinese cases. However, in a pooled sample including data from the literature the spectrum of mutations occurring on maternally and paternally derived chromosomes differed significantly. The excess we found of ‘single base pair gains or losses' on maternally derived MECP2 gene alleles suggests that this mutational category is associated with an elevated risk of gonadal mosaicism, which has implications for genetic counseling.
Wildlife managers often have a good understanding of the threats faced by populations, but they need to know the intensity of management required for populations to survive. Managers therefore need ...quantitative projections for populations under different management regimes rather than just qualitative comparisons. However, quantitative projections are subject to tremendous uncertainty, particularly for small populations monitored for short time spans. We assess the level of predator control needed for a reintroduced population of North Island robins (Petroica longipes) to grow, accounting for uncertainty associated with parameter estimation, model structure, and demographic stochasticity. The robin population grew when exotic rats were reduced to low levels (<10% of footprint tunnels tracked in 24 hr) by regular maintenance of poison bait stations. However, the population declined after baiting was stopped 3 years after the reintroduction (March 2002), and it had fallen to 4 pairs by September 2004. We created a simulation model incorporating relationships between vital rates (survival and fecundity) of the robin population and rat tracking rate estimated from 5 years of data. We ran the model 10,000 times at each rat tracking rate, with vital rates sampled from distributions (defined by estimates and standard errors) at the start of each run. Output from a deterministic model suggested that λ (finite rate of increase) would be >1 if rat tracking were <20%, and up to 1.2 with rat tracking at 1%. However, 95% confidence intervals for λ extended <1 at any tracking rate. With demographic stochasticity added, there was >20% probability of further decline in 5 years even when the expected λ was 1.2. With all forms of uncertainty included, 41% of simulations projected a further decline over 5 years if the rat tracking rate were 10%. This proportion was reduced to 30% if initial population size was increased to 20 pairs. Our analysis therefore showed it was most likely that the robin population would grow if intensive rat control were reinstated, particularly if the population was supplemented, but there was substantial risk the population would continue to decline under such management.
In the first 20 orbits of the Juno spacecraft around Jupiter, we have identified a variety of wave‐like features in images made by its public‐outreach camera, JunoCam. Because of Juno's unprecedented ...and repeated proximity to Jupiter's cloud tops during its close approaches, JunoCam has detected more wave structures than any previous surveys. Most of the waves appear in long wave packets, oriented east‐west and populated by narrow wave crests. Spacing between crests were measured as small as ~30 km, shorter than any previously measured. Some waves are associated with atmospheric features, but others are not ostensibly associated with any visible cloud phenomena and thus may be generated by dynamical forcing below the visible cloud tops. Some waves also appear to be converging, and others appear to be overlapping, possibly at different atmospheric levels. Another type of wave has a series of fronts that appear to be radiating outward from the center of a cyclone. Most of these waves appear within 5° of latitude from the equator, but we have detected waves covering planetocentric latitudes between 20°S and 45°N. The great majority of the waves appear in regions associated with prograde motions of the mean zonal flow. Juno was unable to measure the velocity of wave features to diagnose the wave types due to its close and rapid flybys. However, both by our own upper limits on wave motions and by analogy with previous measurements, we expect that the waves JunoCam detected near the equator are inertia‐gravity waves.
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