Density-dependent foraging and colony growth in a pelagic seabird species under varying environmental conditions

Intra-specific competition for food resources affects both foraging behaviour and population growth rates in many species, highlighting a need to better understand how changing environmental conditions affect individuals in populations of different sizes. Using chick-rearing northern gannets as a model, we examined the influence of colony size on per capita population growth rates over 2 time periods (1994-2000 and 2000-2009) and on foraging trip durations in each of 2 years (2000 and 2009) at 10 colonies in 2 separate regions of the UK and Ireland (the North Sea and the Celtic/Irish Sea). The slope of the relationship between population size and foraging trip duration in 2009 was less than one quarter of that in 2000, suggesting a much weaker influence of population size in 2009, presumably due to less intense intra-specific competition for prey resources at sea. There was also regional variation, with colonies in the Celtic/Irish Sea growing substantially slower for their size over the period between 2000 and 2009 than did colonies bordering the North Sea, whilst observed trip durations in 2009 were on average 13% shorter than predicted from population size at colonies bordering the North Sea, but 32% longer than predicted at colonies in the Celtic and Irish Seas. These data suggest less favourable conditions for gannets in the latter region in recent years, and that annual variation in trip durations will be particularly marked at large colonies, making them especially vulnerable to adverse effects of low prey availability at sea

Energy stress-mediated cytotoxicity in tuberous sclerosis complex 2-deficient cells with nelfinavir and mefloquine treatment

To find new anti-cancer drug therapies, we wanted to exploit homeostatic vulnerabilities within Tuberous Sclerosis Complex 2 (TSC2)-deficient cells with mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. We show that nelfinavir and mefloquine synergize to selectively evoke a cytotoxic response in TSC2-deficient cell lines with mTORC1 hyperactivity. We optimize the concentrations of nelfinavir and mefloquine to a clinically viable range that kill cells that lack TSC2, while wild-type cells tolerate treatment. This new clinically viable drug combination causes a significant level of cell death in TSC2-deficient tumor spheroids. Furthermore, no cell recovery was apparent after drug withdrawal, revealing potent cytotoxicity. Transcriptional profiling by RNA sequencing of drug treated TSC2-deficient cells compared to wild-type cells suggested the cytotoxic mechanism of action, involving initial ER stress and an imbalance in energy homeostatic pathways. Further characterization revealed that supplementation with methyl pyruvate alleviated energy stress and reduced the cytotoxic effect, implicating energy deprivation as the trigger of cell death. This work underpins a critical vulnerability with cancer cells with aberrant signaling through the TSC2-mTORC1 pathway that lack flexibility in homeostatic pathways, which could be exploited with combined nelfinavir and mefloquine treatment

Translation, validity and reliability of the British Sign Language (BSL) version of the EQ-5D-5L.

PURPOSE: To translate the health questionnaire EuroQol EQ-5D-5L into British Sign Language (BSL), to test its reliability with the signing Deaf population of BSL users in the UK and to validate its psychometric properties. METHODS: The EQ-5D-5L BSL was developed following the international standard for translation required by EuroQol, with additional agreed features appropriate to a visual language. Data collection used an online platform to view the signed (BSL) version of the tests. The psychometric testing included content validity, assessed by interviewing a small sample of Deaf people. Reliability was tested by internal consistency of the items and test-retest, and convergent validity was assessed by determining how well EQ-5D-5L BSL correlates with CORE-10 BSL and CORE-6D BSL. RESULTS: The psychometric properties of the EQ-5D-5L BSL are good, indicating that it can be used to measure health status in the Deaf signing population in the UK. Convergent validity between EQ-5D-5L BSL and CORE-10 BSL and CORE-6D BSL is consistent, demonstrating that the BSL version of EQ-5D-5L is a good measure of the health status of an individual. The test-retest reliability of EQ-5D-5L BSL, for each dimension of health, was shown to have Cohen's kappa values of 0.47-0.61; these were in the range of moderate to good and were therefore acceptable. CONCLUSIONS: This is the first time EQ-5D-5L has been translated into a signed language for use with Deaf people and is a significant step forward towards conducting studies of health status and cost-effectiveness in this population

Eukaryotic Plankton Communities Across Reef Environments in Bocas del Toro Archipelago, Panamá

Variation in light and temperature can influence the genetic diversity and structure of marine plankton communities. While open-ocean plankton communities receive much scientific attention, little is known about how environmental variation affects plankton communities on tropical coral reefs. Here, we characterize eukaryotic plankton communities on coral reefs across the Bocas del Toro Archipelago, Panama´. Temperature loggers were deployed, and midday light levels were measured to quantify environmental differences across reefs at four inshore and four offshore sites (Inshore = Punta Donato, Smithsonian Tropical Research Institute (STRI) Point, Cristobal, Punta Laurel and Offshore = Drago Mar, Bastimentos North, Bastimentos South, and Cayo de Agua). Triplicate vertical plankton tows were collected midday, and high-throughput 18S ribosomal DNA metabarcoding was leveraged to investigate the relationship between eukaryotic plankton community structure and inshore/offshore reef environments. Plankton communities from STRI Point were additionally characterized in the morning (* 08:00), midday (* 12:00), and late-day (* 16:00) to quantify temporal variation within a single site. We found that inshore reefs experienced higher average seawater temperatures, while offshore sites offered higher light levels, presumably associated with reduced water turbidity on reefs further from shore. These significant environmental differences between inshore and offshore reefs corresponded with overall plankton community differences. We also found that temporal variation played a structuring role within these plankton communities, and conclude that time of community sampling is an important consideration for future studies. Follow-up studies focusing on more intensive sampling efforts across space and time, coupled with techniques that can detect more subtle genetic differences between and within communities will more fully capture plankton dynamics in this region and beyond

BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production.

BACKGROUND: Bone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH

Yield of Smear Microscopy and Radiological Findings of Male and Female Patients with Tuberculosis in Abuja, Nigeria

Objective. To describe the yield of smear-microscopy and radiological findings by male and female patients with symptoms of tuberculosis in Abuja, Nigeria. Methods. Patients ≥15 years old with cough for >3 weeks submitted 3 sputum samples for smear microscopy. One specimen was cultured using MGIT-960. All patients had lung X-rays and screened for HIV. Results. were more likely to be smear-positive than females (262/774 [34%] and 137/547 [25%], P < .01), but similar proportions of males and females were culture-positive (437/691 [63%] and 294/495 [59%], P = .09). 317/626 (50.6%) males and 249/419 (59.4%) females were HIV-positive (P < .005). Among culture-positives patients, HIV-infected males were less likely to have positive smears than HIV-negative males (49.2% versus 66%, P = .001). Among females, smear positivity did not vary with HIV (46.4% for HIV-positive and 52.9% for HIV-negative, P = .38). Of 274 culture-confirmed TB cases, 226 (82.5%) had cavities, and 271 (99%) had ≥1 lung areas affected. HIV-positive males were more likely to have lung cavities than HIV-positive females (85% versus 69%, P < .04) and to have ≥3 lung areas affected (P = .03). Conclusion. Differences in the yield of smear-microscopy, culture and X-rays on presentation are due to several factors including HIV coinfection and gender

Bar Evolution Over the Last Eight Billion Years: A Constant Fraction of Strong Bars in GEMS

One third of present-day spirals host optically visible strong bars that drive their dynamical evolution. However, the fundamental question of how bars evolve over cosmological times has yet to be addressed, and even the frequency of bars at intermediate redshifts remains controversial. We investigate the frequency of bars out to z~1.0 drawing on a sample of 1590 galaxies from the GEMS survey, which provides morphologies from HST ACS two-color images, and highly accurate redshifts from the COMBO-17 survey. We identify spiral galaxies using the Sersic index, concentration parameter, and rest-frame color. We characterize bars and disks by fitting ellipses to F606W and F850LP images, taking advantage of the two bands to minimize bandpass shifting. We exclude highly inclined (i>60 deg) galaxies to ensure reliable morphological classifications, and apply completeness cuts of M_v <= -19.3 and -20.6. More than 40% of the bars that we detect have semi major axes a<0.5" and would be easily missed in earlier surveys without the small PSF of ACS. The bars that we can reliably detect are fairly strong (with ellipticities e>=0.4) and have a in the range ~1.2-13 kpc. We find that the optical fraction of such strong bars remains at ~(30% +- 6%) from the present-day out to look-back times of 2-6 Gyr (z~0.2-0.7) and 6-8 Gyr (z~0.7-1.0); it certainly shows no sign of a drastic decline at z>0.7. Our findings of a large and similar bar fraction at these three epochs favor scenarios in which cold gravitationally unstable disks are already in place by z~1, and where on average bars have a long lifetime (well above 2 Gyr). The distributions of structural bar properties in the two slices are, however, not statistically identical and therefore allow for the possibility that the bar strengths and sizes may evolve over time.Comment: Accepted by ApJ Letters, to appear in Nov 2004 issue. Minor revisions,updated reference

Histone deacetylase inhibitor trichostatin A sensitises cisplatin-resistant ovarian cancer cells to oncolytic adenovirus

Ovarian cancer is often termed a silent killer due to the late onset of symptoms. Whilst patients initially respond to chemotherapy, they rapidly develop chemo-resistance. Oncolytic adenoviruses (OAds) are promising anti-cancer agents engineered to “hijack” the unique molecular machinery of cancer cells enabling tumour-selective viral replication. This allows spread to adjacent cells and amplification of oncolysis within the tumour. OAds represent an excellent opportunity for ovarian cancer therapy via intra-peritoneal delivery, however the efficacy of OAds thus far is limited. Here, we evaluate chromatin (histone) modification in chemo-resistant cells and its relationship to Ad efficacy (wild-type or oncolytic Ad). In contrast to cisplatin-sensitive A2780 cells that show an efficient reduction of cell viability by Ad in the presence of cisplatin, cisplatin-resistant A2780/cp70 cells show diminishing Ad-mediated reduction of cell viability with escalating doses of cisplatin. Histone deacetylase (HDAC)-2 and to a lesser extent HDAC1 were up-regulated in cisplatin-resistant but not cisplatin-sensitive cells. Cisplatin-resistant cells treated with a pan-HDAC inhibitor trichostatin A (TsA) significantly enhanced Ad-mediated reduction of cell viability in the presence of cisplatin. Cells treated with TsA alone did not reduce cell viability suggesting these findings are Ad-dependent. Thus, we identify HDAC inhibition as a potential means to sensitise cisplatin-resistant ovarian cancer cells to virotherapies, an observation that may offer improved outcomes for patients with late stage, chemotherapy-resistant ovarian cancer

Cyclists in shared bus lanes: could there be unrecognised impacts on bus journey times?

This paper contributes to debates around improving the modelling of cycles, through an exploratory case study of bus–cycle interactions in London. This case study examines undocumented delays to buses caused by high volumes of cyclists in bus lanes. It has generally been assumed that cyclists do not noticeably delay buses in shared lanes. However, in many contexts where cyclists routinely share bus lanes, cyclist numbers have historically been low. In some such places, bus lanes are now seeing very high volumes of cyclists, far above those previously studied. This may have implications for bus – and cycle – journey times, but traditionally traffic modelling has not represented the effects of such interactions well. With some manipulation of parameters taken from models of other cities, the model described here demonstrates that cycles can cause significant delays to buses in shared lanes, at high cycling volumes. These delays are likely to become substantially larger if London's cycling demographic becomes more diverse, because cyclist speeds will decline. Hence bus journey time benefits may derive from separating cycles from buses, where cycle flows are high. The project also suggests that microsimulation modelling software, as typically used, remains problematic for representing cyclists