Metabolism-dependent mutagenicity of two structurally similar tobacco-specific nitrosamines (N-nitrosonornicotine and N-nitrosoanabasine) in human cells, partially different CYPs being activating enzymes.

N-nitrosonornicotine (NNN) and N-nitrosoanabasine (NAB) are both tobacco-specific nitrosamines bearing two heterocyclic amino groups, NAB bearing an extra -CH2- group (conferring a hexa- rather than penta-membered cycle) but with significantly decreased carcinogenicity. However, their activating enzymes and related mutagenicity remain unclear. In this study, the chemical-CYP interaction was analyzed by molecular docking, thus the binding energies and conformations of NNN for human CYP2A6, 2A13, 2B6, 2E1 and 3A4 appeared appropriate as a substrate, so did NAB for human CYP1B1, 2A6, 2A13 and 2E1. The micronucleus test in human hepatoma (HepG2) cells with each compound (62.5-1000 µM) exposing for 48 h (two-cell cycle) was negative, however, pretreatment with bisphenol AF (0.1-100 nM, CYPs inducer) and ethanol (0.2% v:v, CYP2E1 inducer) potentiated micronucleus formation by both compounds, while CITCO (1 µM, CYP2B6 inducer) selectively potentiated that by NNN. In C3A cells (endogenous CYPs enhanced over HepG2) both compounds induced micronucleus, which was abolished by 1-aminobenzotriazole (60 µM, CYPs inhibitor) while unaffected by 8-methoxypsoralen (1 µM, CYP2A inhibitor). Consistently, NNN and NAB induced micronucleus in V79-derived recombinant cell lines expressing human CYP2B6/2E1 and CYP1B1/2E1, respectively, while negative in those expressing other CYPs. By immunofluorescent assay both compounds selectively induced centromere-free micronucleus in C3A cells. In PIG-A assays in HepG2 cells NNN and NAB were weakly positive and simply negative, respectively; however, in C3A cells both compounds significantly induced gene mutations, NNN being slight more potent. Conclusively, both NNN and NAB are mutagenic and clastogenic, depending on metabolic activation by partially different CYP enzymes.

Artificial light at night correlates with seabird groundings: mapping city lights near a seabird breeding hotspot.

Artificial light at night (ALAN) is a growing conservation concern for seabirds, which can become disoriented and grounded by lights from buildings, bridges and boats. Many fledgling seabirds, especially Procellariiformes such as petrels and shearwaters, are susceptible to light pollution. The Hauraki Gulf, a seabird hotspot located near Tamaki Makaurau/Auckland, Aotearoa-New Zealand's largest urban city, with a considerable amount of light pollution and regularly documented events of seabird groundings. We aim to identify the characteristics of locations especially prone to seabird groundings. We used an online database of seabirds taken to a wildlife rescue facility by the public to map 3 years of seabird groundings and test for correlations between seabird groundings and the natural night sky brightness. We found that areas with lower amounts of natural night sky brightness and greater light pollution often had a higher number of seabirds grounded. Further, we identified important seasonal patterns and species differences in groundings. Such differences may be a by-product of species ecology, visual ecology and breeding locations, all of which may influence attraction to lights. In general, seabird groundings correlate with the brightness of the area and are species-specific. Groundings may not be indicative of human or seabird population abundance considering some areas have a lower human population with high light levels and had high amounts of seabird groundings. These findings can be applied worldwide to mitigate groundings by searching and targeting specific brightly lit anthropogenic structures. Those targeted structures and areas can then be the focus of light mitigation efforts to reduce seabird groundings. Finally, this study illustrates how a combination of community science, and a concern for seabirds grounded from light attraction, in addition to detailed animal welfare data and natural night sky brightness data can be a powerful, collaborative tool to aid global conservation efforts for highly-at-risk animals such as seabirds.

Cat ownership and Proximity to Significant Ecological Areas Influence Attitudes Towards Cat Impacts and Management Practices.

Cat ownership is increasing globally, representing a growing threat to urban wildlife. Although some cities have policies and strategies for managing owned cats, the companionship value placed on cats makes such management contentious. Prioritizing cat management in urban residential zones adjacent to large significant ecological areas (SEAs; areas designated on the basis of representativeness, threat status or rarity, diversity, connectedness, or uniqueness) could maximize return on management effort. Residents in these areas may place a relatively higher value on nature than residents in suburbs with minimal or no SEAs, and therefore may be comparatively more likely to perceive cats' wildlife impacts as important. We used a quantitative survey to compare SEA and non-SEA suburbs' residents' attitudes towards cat impacts and management in Tamaki Makaurau-Auckland, Aotearoa-New Zealand. Participants were asked to rate the importance of different feral and owned cat impacts, the importance of feral-cat control in different locations, and various ownership behaviors in terms of acceptability and best practice. SEA suburb residents placed more importance on wildlife predation impacts of feral cats and were more likely to regard 24-h cat confinement as best practice than non-SEA suburb residents. However, we also found that cat ownership and youth were negatively associated with perception of cat impacts, and owners were less likely to accept belled collars and cat confinement than nonowners. Therefore, although targeting SEA adjacent areas for cat management holds promise for reducing resident contention, proximity to such areas is a relatively minor influence for cat owners.

Photocatalytic degradation of ibuprofen over BiOCl nanosheets with identification of intermediates.

Photocatalysis directed at the removal of persistent organic pollutants, including pharmaceuticals, has been the subject of intense recent research. Bismuth oxychloride (BiOCl) has emerged as a potential alternative to traditional photocatalysts and has shown competitive removal efficiencies. However, pathways responsible for BiOCl photodegradation have not been well characterized. The present work is the first to determine, using LC-MS/MS analysis, the pathways by which BiOCl removes ibuprofen (IBP) from water. HPLC-DAD and LC-MS/MS analyses show that BiOCl converts IBP to two primary photochemical products, 4-isobutylacetophenone (IBAP) and 1-(4-isobutylphenyl)ethanol (IBPE). The reactivity for BiOCl is attributed to interactions of the carboxylic acid group of IBP with holes in the valence band. Hydroxylated-IBP was not detected in BiOCl photocatalytic degradation experiments which would be expected in a process driven by the formation and reactivity of reactive oxygen species. These data were used to formulate a photocatalytic degradation pathway for IBP and highlight the importance of studying both primary and secondary degradation reactions for photocatalytic studies.

Middle ear mechanics of cartilage tympanoplasty evaluated by laser holography and vibrometry.

GOALS: To assess the effects of thickness and position of cartilage used to reconstruct the tympanic membrane (TM) using a novel technique, time-averaged laser holography. BACKGROUND: Cartilage is commonly used in TM reconstruction to prevent formation of retraction pockets. The thickness, position, and shape of the cartilage graft may adversely affect TM motion and hearing. We sought to systematically investigate these parameters in an experimental setting. METHODS: Computer-assisted optoelectronic laser holography was used in 4 human cadaveric temporal bones to study sound-induced TM motion for 500 Hz to 8 kHz. Stapes velocity was measured with a laser Doppler vibrometer. Baseline (control) measurements were made with the TM intact. Measurements were repeated after a 0.5- or 1.0-mm-thick oval piece of conchal cartilage was placed on the medial TM surface in the posterior-superior quadrant. The cartilage was rotated so that it was either in contact with the bony tympanic rim and manubrium or not. RESULTS: At frequencies less than 4 kHz, the cartilage graft had only minor effects on the overall TM fringe patterns. The different conditions had no effects on stapes velocity. Greater than 4 kHz, TM motion was reduced over the grafted TM, both with 0.5- and 1.0-mm-thick grafts. No significant differences in stapes velocity were seen with the 2 different thicknesses of cartilage compared with control. CONCLUSION: Computer-assisted optoelectronic laser holography is a promising technique to investigate middle ear mechanics after tympanoplasty. Such positioning may prevent postoperative TM retraction. These findings and conclusions apply to cartilage placed in the posterior-superior TM quadrant.

Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism.

It has recently been shown that loss-of-function mutations of the G protein-coupled receptor (GPR)54 lead to isolated hypogonadotropic hypogonadism (IHH) in mice and humans. Such mutations are thought to be rare, even within the clinical IHH population, and only a handful of alleles have been described, making further screening of IHH populations imperative. We examined the genes encoding GPR54 and its putative endogenous ligand, kisspeptin-1, for mutations in a cohort of 30 patients with normosmic HH or delayed puberty. One subject with HH, of mixed Turkish-Cypriot and Afro-Caribbean ancestry, was found to be a compound heterozygote for two previously undescribed missense mutations in GPR54: cysteine 223 to arginine (C223R) in the fifth transmembrane helix and arginine 297 to leucine (R297L) in the third extracellular loop. Assessed in vitro using a previously described sensitive signaling assay in cells stably expressing GPR54, the C223R variant was found to exhibit profoundly impaired signaling, whereas the R297L variant showed a mild reduction in ligand-stimulated activity across the ligand dose range. These novel mutations provide further evidence that human HH may be caused by loss-of-function mutations in GPR54.

Activation of the interleukin 2 receptor: a possible role for tyrosine phosphatases.

Engagement of interleukin-2 (IL-2) mediates the heterodimeridation of the common beta chain (beta(c)) and common gamma chain (gamma(c)) of the IL-2 receptor (IL-2R). This is sufficient and necessary for receptor activation and signal transduction. It is generally held that the IL-2R is activated by the trans-activity of the protein tyrosine kinases (PTKs) Jak1 and Jak3 associated with beta(c) and gamma(c) respectively. Transduction of proliferative signals requires Jak3 activity. A Jak3 independent signalling pathway involving p56(lck), generating anti-apoptotic signals, can be observed and requires the PROX domain of gamma(c). p56(lck) can be activated by dephosphorylation of an inhibitory carboxyl terminal phosphorylated tyrosine residue (Y505). We propose that this is mediated by a PROX domain associated protein tyrosine phosphatase (PTP). Activation of p56(lck) alone is insufficient for transduction of proliferative signals and thus works in concert with Jak3 mediated receptor activation. This indicates that both gamma(c) domains are vital for signal transduction.

Displaced subcapital fractures of the femur: a prospective randomized comparison of internal fixation, hemiarthroplasty and total hip replacement.

In a prospective trial of 278 patients aged over 65 years, treatment of displaced subcapital fractures was randomly allocated to closed reduction and internal fixation with a sliding compression screwplate, Moore hemiarthroplasty, or total hip treatment with a Howse semicaptive prosthesis. One year after operation there was little difference between the three groups in mortality (25 per cent) or general complications. The revision rate within the first year was highest for internal fixation (25 per cent), but many of the replacements also required a further anaesthetic for reduction of a dislocation (Moore, 11 per cent; Howse 12.5 per cent). Total hip replacement resulted in the least pain and most mobility at 1 year, while hemiarthroplasty was worst in these respects. We conclude that internal fixation and particularly primary total hip replacement should be given serious consideration in the management of the elderly patient with a displaced subcapital fracture.