A WC/WO star exploding within an expanding carbon-oxygen-neon nebula.

The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars2,3, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion4. Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients5-8. Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.

Comparing genetic diversity and demographic history in co-distributed wild South American camelids.

Vicuñas and guanacos are two species of wild South American camelids that are key ruminants in the ecosystems where they occur. Although closely related, these species feature differing ecologies and life history characters, which are expected to influence both their genetic diversity and population differentiation at different spatial scales. Here, using mitochondrial and microsatellite genetic markers, we show that vicuña display lower genetic diversity within populations than guanaco but exhibit more structure across their Peruvian range, which may reflect a combination of natural genetic differentiation linked to geographic isolation and recent anthropogenic population declines. Coalescent-based demographic analyses indicate that both species have passed through a strong bottleneck, reducing their effective population sizes from over 20,000 to less than 1000 individuals. For vicuña, this bottleneck is inferred to have taken place ~3300 years ago, but to have occurred more recently for guanaco at ~2000 years ago. These inferred dates are considerably later than the onset of domestication (when the alpaca was domesticated from the vicuña while the llama was domesticated from the guanaco), coinciding instead with a major human population expansion following the mid-Holocene cold period. As importantly, they imply earlier declines than the well-documented Spanish conquest, where major mass mortality events were recorded for Andean human and camelid populations. We argue that underlying species' differences and recent demographic perturbations have influenced genetic diversity in modern vicuña and guanaco populations, and these processes should be carefully evaluated in the development and implementation of management strategies for these important genetic resources.

A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind.

The explosive fate of massive Wolf-Rayet stars (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections. Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 10(12) centimetres, as expected for some WRSs. The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions.

Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis.

Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3(+) T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3(+) T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3(+) T in RA.

X-ray illumination of the ejecta of supernova 1987A.

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.

Mitochondrial phylogeography and demographic history of the vicuña: implications for conservation.

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275,000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22 degrees S) dry Andes 14-12,000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29 degrees S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts.

Genetic analysis reveals the wild ancestors of the llama and the alpaca.

The origins of South America's domestic alpaca and llama remain controversial due to hybridization, near extirpation during the Spanish conquest and difficulties in archaeological interpretation. Traditionally, the ancestry of both forms is attributed to the guanaco, while the vicuña is assumed never to have been domesticated. Recent research has, however, linked the alpaca to the vicuña, dating domestication to 6000-7000 years before present in the Peruvian Andes. Here, we examine in detail the genetic relationships between the South American camelids in order to determine the origins of the domestic forms, using mitochondrial (mt) and microsatellite DNA. MtDNA analysis places 80% of llama and alpaca sequences in the guanaco lineage, with those possessing vicuña mtDNA being nearly all alpaca or alpaca-vicuña hybrids. We also examined four microsatellites in wild known-provenance vicuña and guanaco, including two loci with non-overlapping allele size ranges in the wild species. In contrast to the mtDNA, these markers show high genetic similarity between alpaca and vicuña, and between llama and guanaco, although bidirectional hybridization is also revealed. Finally, combined marker analysis on a subset of samples confirms the microsatellite interpretation and suggests that the alpaca is descended from the vicuña, and should be reclassified as Vicugna pacos. This result has major implications for the future management of wild and domestic camelids in South America.

Mechanisms of transcriptional regulation by Runt domain proteins.

Runt domain proteins have vital roles in regulating transcription in developmental pathways extending from sex determination and segmentation in fruit fly embryos to the development of blood and bone in mammals. Many of the insights into the mechanisms by which these proteins act to regulate transcription originate either from studies on the Drosophila runt gene, the founding member of this family, or from work on the mammalian PEBP2/CBF transcription factor. Genetic experiments in the Drosophila system reveal that runt functions both to activate and to repress transcription of different downstream target genes and indicate that different mechanisms are used in the regulation of different specific downstream target genes. These studies have also identified other nuclear factors that work with Runt in some of these pathways. Studies in mammalian systems have provided additional evidence for the complexity of transcriptional regulation by Runt domain proteins and have identified other transcription factors that cooperate with Runt domain proteins to regulate the activity of different specific cis-regulatory enhancers. The emerging view from studies in both systems is that these proteins act as context-dependent regulators of transcription, activating or repressing gene expression dependent upon the constititution of a particular promoter/enhancer in a particular cell type. These results have yielded new insights into the molecular mechanisms that control animal development and provide a framework for investigating fundamental issues in eukaryotic transcriptional regulation.

A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration.

The disks of vertebrate photoreceptors are produced by outgrowths of the plasma membrane. Hence genes that encode retinal proteins targeted to plasma membrane protrusions represent candidates for inherited retinal degenerations. One such candidate is the gene encoding human prominin (mouse)-like 1 (PROML1, previously known as AC133 antigen) which belongs to the prominin family of 5-transmembrane domain proteins. Murine prominin (prom) shows a strong preference for plasma membrane protrusions in a variety of epithelial cells whereas PROML1 is expressed in retinoblastoma cell lines and adult retina. In the present study, molecular genetic analyses of a pedigree segregating for autosomal recessive retinal degeneration indicated that the affected individuals were homozygous for a nucleotide 1878 deletion in PROML1. This alteration is predicted to result in a frameshift at codon 614 with premature termination of translation. Expression of a similar prom deletion mutant in CHO cells indicated that the truncated protein does not reach the cell surface. Immunocytochemistry revealed that prom is concentrated in the plasma membrane evaginations at the base of the outer segments of rod photoreceptors. These findings suggest that loss of prominin causes retinal degeneration, possibly because of impaired generation of the evaginations and/or impaired conversion of the evaginations to disks.

Sequence requirements for upregulated expression of Drosophila hsp70 transgenes during aging.

hsp70 protein and hsp70:lacZ fusion reporters are upregulated during aging and in response to oxidative stress in the thorax of Drosophila. hsp70 expression was increased during aging in each of seven different Drosophila genetic backgrounds tested, 2.6-4.8-fold. DNA sequence requirements were investigated by analysis of nine distinct hsp70:lacZ fusion reporter constructs in multiple independent transgenic lines. hsp70 sequences -194 to +276 supported an average 2.7-fold increase during aging. This increase was reduced or eliminated by deletion or point mutation of the heat shock response elements, consistent with a transcriptional mechanism. Similar sequence requirements were observed for increased expression in response to catalase null mutation as a model of oxidative stress. hsp70 5'UTR sequences were required for efficient basal expression of transgenes, but were not sufficient to confer detectable upregulation during aging. Inclusion of additional hsp70 coding region sequences from +276 to + 1011 created a larger hsp70:lacZ fusion protein and had two effects: dramatic reduction of the overall expression level of the fusion protein, and an additional three to fourfold upregulation during aging. These results suggest that the coding region sequences reduce fusion protein abundance and that this negative effect decreases as a function of age. The data support a model for increased expression of hsp70 transgenes during aging involving both transcriptional and posttranscriptional components.

Genetic variation within the ovine cystic fibrosis transmembrane conductance regulator gene.

We report here the results of a preliminary screening programme to identify natural mutations in the ovine cystic fibrosis transmembrane conductance regulator (CFTR) gene. Nine regions of the ovine CFTR gene were screened, corresponding to human CFTR gene exons 4, 6b, 7, 9, 10, 11, 12, 17b and 20. DNA samples from up to 2000 individual sheep were examined by single-stranded conformation polymorphism (SSCP) of each exon. In addition to the mutation (R297Q) reported previously, we have found several interesting variants, including intronic DNA variants and exonic polymorphisms.

Doxycycline-induced transgene expression during Drosophila development and aging.

The "reverse" tetracycline repressor (rtR) binds a specific DNA element, the tetracycline operator (tetO), only in the presence of tetracycline, or derivatives such as doxycycline (dox). Fusion of rtR to the transcriptional activation domain of herpes virus protein VP16 produces a eukaryotic transactivator protein (rtTA). rtTA has previously been shown to allow dox-dependent transcription of transgenes linked to tetO sequences in mammals. To adapt this system to Drosophila, the Actin5C promoter was used to drive constitutive expression of rtTA in transgenic flies. Three reporter constructs, each encoding E. coli beta-galactosidase (beta-gal), were also introduced into transgenic flies. In one reporter seven tetO sequences were fused to the Adh core promoter. The other two reporter constructs contain seven tetO sequences fused to the hsp70 core promoter. Feeding of transgenic Drosophila containing the rtTA construct and any one of the three reporter constructs with dox caused up to 100-fold induction of beta-gal. Dox induced beta-gal expression in all tissues, in larvae and in young and senescent adults. Induction of beta-gal in adults had no detectable effect on life span. These results suggest the potential usefulness of this system for testing specific genes for effects on Drosophila development and aging.

Industrial high-voltage electrical burn of the skull, a preventable injury.

Deep burns of the scalp and skull are often caused by high-voltage electrical injuries. Patients with such injuries should be referred to regional burn centers that are prepared to excise necrotic burn tissue and cover the devitalized bone with a well-vascularized flap. Strategies for prevention of these electrical burns are discussed.

Oral squamous cell carcinoma in association with dental osseointegrated implants. An unusual occurrence.

The major risk factors for developing oral cavity squamous cell carcinoma in the United States include smoking, alcohol, syphilis, and herpes simplex virus type 1. It is difficult to locate a report of squamous cell carcinoma arising in association with osseointegrated dental implants, despite their frequent use. We report an unusual series of 3 cases of squamous cell carcinoma arising around an implant.

Potential toxicity of retrograde uterine passage of particulate matter.

Dusting powders are commonly used on surgical gloves, examination gloves, and condoms. In addition, they are used in diaphragms, sanitary napkins, and toiletries. These dusting powders can gain access to the abdominal cavity through the vagina or through surgical intervention. The toxicity of these dusting powders in the abdominal cavity can be divided into acute and chronic complications that may be life-threatening. The use of medical and surgical products without dusting powders is strongly recommended.

Evolution of hydrogel polymers as contact lenses, surface coatings, dressings, and drug delivery systems.

Hydrogel polymers are hydrophilic resins that display excellent biocompatibility, which has allowed their application in diverse fields of surgery and medicine. The original hydrogel polymer, a copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate, was developed by Wichterle and Lim in 1954. The development of the first soft hydrogel contact lenses by Wichterle in 1961 represented the first successful clinical application of hydrogel polymers and remains one of the most important uses of hydrogels today. The biocompatibility of hydrogel polymers may be adapted to diverse tissue types by small variations in the makeup of the polymer, including varying the type and amount of monomers and differing the amounts and characteristics of the cross-linking agents used to create the polymer chains. Hydrogels have been successfully developed for use as coatings, soft contact lenses, wound dressings, and drug delivery systems.

Muscle-specific expression of Drosophila hsp70 in response to aging and oxidative stress.

Induction of Drosophila hsp70 protein was detected during aging in flight muscle and leg muscle in the absence of heat shock, using an hsp70-specific monoclonal antibody, and in transgenic flies containing hsp70-beta-galactosidase fusion protein reporter constructs. While hsp70 and reporter proteins were induced during aging, hsp70 message levels were not, indicating that aging-specific induction is primarily posttranscriptional. In contrast, hsp22 and hsp23 were found to be induced during aging at the RNA level and with a broader tissue distribution. The same muscle-specific hsp70 reporter expression pattern was observed in young flies mutant for catalase (H2O2:H2O2 oxidoreductase, EC 1.11.1.6). In catalase (cat) hypomorphic lines where flies survived to older ages, the time course of hsp70 reporter expression during aging was accelerated, and the initial and ultimate levels of expression were increased. The hsp70 reporter was also induced in young flies mutant for copper/zinc superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1). Taken together, the results suggest that aging-specific hsp70 expression may be a result of oxidative damage.

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.

Molecular evolution of the family Camelidae: a mitochondrial DNA study.

We report the first molecular evolutionary analysis of the family Camelidae by analysing the full DNA sequence of the mitochondrial cytochrome b gene. Estimates for the time of divergence of the Old World (Camelini) and New World (Lamini) tribes obtained from sequence data are in agreement with those derived from the fossil record. The DNA sequence data were also used to test current hypotheses concerning the ancestors of the domesticated llama and alpaca. The results show that hybridization has occurred in the ancestry of both domesticated camelids, obscuring the origin of the domestic species.