An observed correlation between plume activity and tidal stresses on Enceladus.

Saturn's moon Enceladus emits a plume of water vapour and micrometre-sized ice particles from a series of warm fissures located near its south pole. This geological activity could be powered or controlled by variations in the tidal stresses experienced by Enceladus as it moves around its slightly eccentric orbit. The specific mechanisms by which these varying stresses are converted into heat, however, are still being debated. Furthermore, it has proved difficult to find a clear correlation between the predicted tidal forces and measured temporal variations in the plume's gas content or the particle flux from individual sources. Here we report that the plume's horizontally integrated brightness is several times greater when Enceladus is near the point in its eccentric orbit where it is furthest from Saturn (apocentre) than it is when near the point of closest approach to the planet (pericentre). More material therefore seems to be escaping from beneath Enceladus' surface at times when geophysical models predict its fissures should be under tension and therefore may be wider open.

The use of Singapore flaps for vaginal reconstruction in women with vaginal stenosis with obstetric fistula: a surgical technique.

Gynecologic and plastic surgeons collaborate to improve vaginal reconstruction for women with vaginal stenosis and obstetric fistula. As these cases occur typically in low-resource settings, the Singapore flap is a useful technique given its reliability, safety, ease of dissection, and minimal need for additional supplies. The fasciocutaneous flap maintains cutaneous innervation and vasculature and does not require stenting. The surgical collaboration has made it possible to provide functional vaginal reconstruction as a part of the overall care of obstetric fistula patients. The technique shows promise for improving sexual function for women with obstetric fistula and may also enhance healing. TWEETABLE ABSTRACT: Gynecologic & plastic surgeons collaborate to improve vaginal reconstruction for women with obstetric fistula.

Spectral properties of Titan's impact craters imply chemical weathering of its surface.

We examined the spectral properties of a selection of Titan's impact craters that represent a range of degradation states. The most degraded craters have rims and ejecta blankets with spectral characteristics that suggest that they are more enriched in water ice than the rims and ejecta blankets of the freshest craters on Titan. The progression is consistent with the chemical weathering of Titan's surface. We propose an evolutionary sequence such that Titan's craters expose an intimate mixture of water ice and organic materials, and chemical weathering by methane rainfall removes the soluble organic materials, leaving the insoluble organics and water ice behind. These observations support the idea that fluvial processes are active in Titan's equatorial regions.

Dynamic auroral storms on Saturn as observed by the Hubble Space Telescope.

We present observations of significant dynamics within two UV auroral storms observed on Saturn using the Hubble Space Telescope in April/May 2013. Specifically, we discuss bursts of auroral emission observed at the poleward boundary of a solar wind-induced auroral storm, propagating at ∼330% rigid corotation from near ∼01 h LT toward ∼08 h LT. We suggest that these are indicative of ongoing, bursty reconnection of lobe flux in the magnetotail, providing strong evidence that Saturn's auroral storms are caused by large-scale flux closure. We also discuss the later evolution of a similar storm and show that the emission maps to the trailing region of an energetic neutral atom enhancement. We thus identify the auroral form with the upward field-aligned continuity currents flowing into the associated partial ring current.

The identification of liquid ethane in Titan's Ontario Lacus.

Titan was once thought to have global oceans of light hydrocarbons on its surface, but after 40 close flybys of Titan by the Cassini spacecraft, it has become clear that no such oceans exist. There are, however, features similar to terrestrial lakes and seas, and widespread evidence for fluvial erosion, presumably driven by precipitation of liquid methane from Titan's dense, nitrogen-dominated atmosphere. Here we report infrared spectroscopic data, obtained by the Visual and Infrared Mapping Spectrometer (VIMS) on board the Cassini spacecraft, that strongly indicate that ethane, probably in liquid solution with methane, nitrogen and other low-molecular-mass hydrocarbons, is contained within Titan's Ontario Lacus.

Surface composition of Hyperion.

Hyperion, Saturn's eighth largest icy satellite, is a body of irregular shape in a state of chaotic rotation. The surface is segregated into two distinct units. A spatially dominant high-albedo unit having the strong signature of H2O ice contrasts with a unit that is about a factor of four lower in albedo and is found mostly in the bottoms of cup-like craters. Here we report observations of Hyperion's surface in the ultraviolet and near-infrared spectral regions with two optical remote sensing instruments on the Cassini spacecraft at closest approach during a fly-by on 25-26 September 2005. The close fly-by afforded us the opportunity to obtain separate reflectance spectra of the high- and low-albedo surface components. The low-albedo material has spectral similarities and compositional signatures that link it with the surface of Phoebe and a hemisphere-wide superficial coating on Iapetus.

SPTLC1 is mutated in hereditary sensory neuropathy, type 1.

Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1.

Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury.

The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD-deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.

Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.

Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.

Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile ALS and has been mapped to human chromosome 2q33. Here we report the identification of two independent deletion mutations linked to ALS2 in the coding exons of the new gene ALS2. These deletion mutations result in frameshifts that generate premature stop codons. ALS2 is expressed in various tissues and cells, including neurons throughout the brain and spinal cord, and encodes a protein containing multiple domains that have homology to RanGEF as well as RhoGEF. Deletion mutations are predicted to cause a loss of protein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS.

Release of volatiles from a possible cryovolcano from near-infrared imaging of Titan.

Titan is the only satellite in our Solar System with a dense atmosphere. The surface pressure is 1.5 bar (ref. 1) and, similar to the Earth, N2 is the main component of the atmosphere. Methane is the second most important component, but it is photodissociated on a timescale of 10(7) years (ref. 3). This short timescale has led to the suggestion that Titan may possess a surface or subsurface reservoir of hydrocarbons to replenish the atmosphere. Here we report near-infrared images of Titan obtained on 26 October 2004 by the Cassini spacecraft. The images show that a widespread methane ocean does not exist; subtle albedo variations instead suggest topographical variations, as would be expected for a more solid (perhaps icy) surface. We also find a circular structure approximately 30 km in diameter that does not resemble any features seen on other icy satellites. We propose that the structure is a dome formed by upwelling icy plumes that release methane into Titan's atmosphere.

Non-recurrent SEPT9 duplications cause hereditary neuralgic amyotrophy.

BACKGROUND: Genomic copy number variants have been shown to be responsible for multiple genetic diseases. Recently, a duplication in septin 9 (SEPT9) was shown to be causal for hereditary neuralgic amyotrophy (HNA), an episodic peripheral neuropathy with autosomal dominant inheritance. This duplication was identified in 12 pedigrees that all shared a common founder haplotype. METHODS AND RESULTS: Based on array comparative genomic hybridisation, we identified six additional heterogeneous tandem SEPT9 duplications in patients with HNA that did not possess the founder haplotype. Five of these novel duplications are intragenic and result in larger transcript and protein products, as demonstrated through reverse transcription-PCR and western blotting. One duplication spans the entire SEPT9 gene and does not generate aberrant transcripts and proteins. The breakpoints of all the duplications are unique and contain regions of microhomology ranging from 2 to 9 bp in size. The duplicated regions contain a conserved 645 bp exon within SEPT9 in which HNA-linked missense mutations have been previously identified, suggesting that the region encoded by this exon is important to the pathogenesis of HNA. CONCLUSIONS: Together with the previously identified founder duplication, a total of seven heterogeneous SEPT9 duplications have been identified in this study as a causative factor of HNA. These duplications account for one third of the patients in our cohort, suggesting that duplications of various sizes within the SEPT9 gene are a common cause of HNA.

Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis.

FUS, EWS, and TAF15 belong to the TET family of structurally similar DNA/RNA-binding proteins. Mutations in the FUS gene have recently been discovered as a cause of familial amyotrophic lateral sclerosis (FALS). Given the structural and functional similarities between the three genes, we screened TAF15 and EWS in 263 and 94 index FALS cases, respectively. No coding variants were found in EWS, while we identified six novel changes in TAF15. Of these, two 24 bp deletions and a R388H missense variant were also found in healthy controls. A D386N substitution was shown not to segregate with the disease in the affected pedigree. A single A31T and two R395Q changes were identified in FALS cases but not in over 1,100 controls. Interestingly, one of the R395Q FALS cases also harbors a TARDBP mutation (G384R). Altogether, these results suggest that additional studies are needed to determine whether mutations in the TAF15 gene represent a cause of FALS.

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor.

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant-induced arthritis.

Organic matter on asteroid 130 elektra.

Infrared absorption spectra of a low-albedo water-rich asteroid appear to show a weak 3.4-micrometer carbon-hydrogen stretching mode band, which suggests the presence of hydrocarbons on asteroid 130 Elektra. The organic extract from the primitive carbonaceous chondritic Murchison meteorite shows similar spectral bands.

The Phase Composition of Triton's Polar Caps.

Triton's polar caps are modeled as permanent nitrogen deposits hundreds of meters thick. Complex temperature variations on Triton's surface induce reversible transitions between the cubic and hexagonal phases of solid nitrogen, often with two coexisting propagating transition fronts. Subsurface temperature distributions are calculated using a two-dimensional thermal model with phase changes. The phase changes fracture the upper nitrogen layer, increasing its reflectivity and thus offering an explanation for the surprisingly high southern polar cap albedo (approximately 0.8) seen during the Voyager 2 flyby. The model has other implications for the phase transition phenomena on Triton, such as a plausible mechanism for the origin of geyser-like plume vent areas and a mechanism of energy transport toward them.

Subsurface energy storage and transport for solar-powered geysers on triton.

The location of active geyser-like eruptions and related features close to the current subsolar latitude on Triton suggests a solar energy source for these phenomena. Solidstate greenhouse calculations have shown that sunlight can generate substantially elevated subsurface temperatures. A variety of models for the storage of solar energy in a sub-greenhouse layer and for the supply of gas and energy to a geyser are examined. "Leaky greenhouse" models with only vertical gas transport are inconsistent with the observed upper limit on geyser radius of approximately 1.5 kilometers. However, lateral transport of energy by gas flow in a porous N(2) layer with a block size on the order of a meter can supply the required amount of gas to a source region approximately 1 kilometer in radius. The decline of gas output to steady state may occur over a period comparable with the inferred active geyser lifetime of five Earth years. The required subsurface permeability may be maintained by thermal fracturing of the residual N2 polar cap. A lower limit on geyser source radius of approximately 50 to 100 meters predicted by a theory of negatively buoyant jets is not readily attained.

Triton: do we see to the surface?

The quantity and physical state of methane and nitrogen in the atmosphere of Neptune's satellite Triton and on the surface are evaluated by means of new telescopic data and laboratory measurements of these volatiles. Methane ice is seen in some spectral regions, indicating that the atmosphere is sufficiently transparent to permit sunlight penetration to the surface. Some of the molecular nitrogen absorption occurs in the atmosphere, though some must occur in condensed nitrogen (liquid or solid) on Triton's surface, or in a thin cloud of condensed nitrogen. The Voyager spacecraft cameras should see the surface of Triton.

Surface composition of Kuiper belt object 1993SC.

The 1.42- to 2.40-micrometer spectrum of Kuiper belt object 1993SC was measured at the Keck Observatory in October 1996. It shows a strongly red continuum reflectance and several prominent infrared absorption features. The strongest absorptions in 1993SC's spectrum occur near 1.62, 1.79, 1.95, 2.20, and 2.32 micrometers in wavelength. Features near the same wavelengths in the spectra of Pluto and Neptune's satellite Triton are due to CH4 on their surfaces, suggesting the presence of a simple hydrocarbon ice such as CH4, C2H6, C2H4, or C2H2 on 1993SC. In addition, the red continuum reflectance of 1993SC suggests the presence of more complex hydrocarbons.