Interactions of fishes with particular reference to coelacanths in the canyons at Sodwana Bay and the St. Lucia Protected Area of South Africa

The deep demersal fish fauna at depths of 100–400min canyons off the St Lucia Marine Protected Area along the north coast of KwaZulu-Natal is compared with similar fish communities at the Comoro Islands and in the Indo-Pacific region. Fifty-four fish species were seen or photographed from the submersible Jago or by the discovery team of scuba divers in the coelacanth, Latimeria chalumnae, habitat of the canyons off Sodwana Bay. An additional 94 fish species known from depths of 100–200 m along the coast of northern KwaZulu-Natal are likely to occur in the canyon habitat. The fish fauna of the Sodwana canyons shares at least 18 species with the deep demersal fish community off tropical coral reefs of the Indo-Pacific region. Thirty-seven of the Sodwana canyon fishes are also known from the coelacanth habitat in the Comoros

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Residual lung lesions after completion of chemotherapy for gestational trophoblastic neoplasia: should we operate?

The significance of residual lung metastasis from malignant gestational trophoblastic neoplasm (GTN) after the completion of chemotherapy is unknown. We currently do not advocate resection of these masses. Here, we investigate the outcome of these patients. Patients with residual lung abnormalities after the completion of treatment for GTN were compared to those who had a complete radiological resolution of the disease. None of the residual masses post-treatment were surgically removed. In all, 76 patients were identified. Overall 53 (70%) patients had no radiological abnormality on CXR or CT after completion of treatment. Eight (11%) patients had residual disease on CXR alone 15 patients had residual disease on CT (19%). During follow-up, two patients (2.6%) relapsed. One of these had had a complete radiological response post-treatment whereas the other had residual disease on CT. Patients with residual lung lesions after completing treatment for GTN do not appear to have an increased chance of relapse compared to those with no residual abnormality. We continue to recommend that these patients do not require pulmonary surgery for these lesions

Improving manual oxygen titration in preterm infants by training and guideline implementation

To study oxygen saturation (SpO2) targeting before and after training and guideline implementation of manual oxygen titration, two cohorts of preterm infants 21%. ABCs where oxygen therapy was given were identified and analyzed. After training and guideline implementation the %SpO2-wtr increased (median interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p 95% did not decrease (73% vs 64%; ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION: Training and guideline implementation in manual oxygen titration improved SpO2 targeting in preterm infants with more time spent within the target range and less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during ABCs were shorter. What is Known: • Oxygen saturation targeting in preterm infants can be challenging and the compliance is low when oxygen is titrated manually. • Hyperoxaemia often occurs after oxygen therapy for oxygen desaturation during apnoeas. What is New: • Training and implementing guidelines improved oxygen saturation targeting and reduced hyperoxaemia. • Training and implementing guidelines improved manual oxygen titration during ABC

Systematic Screening of Drosophila Deficiency Mutations for Embryonic Phenotypes and Orphan Receptor Ligands

This paper defines a collection of Drosophila deletion mutations (deficiencies) that can be systematically screened for embryonic phenotypes, orphan receptor ligands, and genes affecting protein localization. It reports the results of deficiency screens we have conducted that have revealed new axon guidance phenotypes in the central nervous system and neuromuscular system and permitted a quantitative assessment of the number of potential genes involved in regulating guidance of specific motor axon branches. Deficiency “kits” that cover the genome with a minimum number of lines have been established to facilitate gene mapping. These kits cannot be systematically analyzed for phenotypes, however, since embryos homozygous for many deficiencies in these kits fail to develop due to the loss of key gene products encoded within the deficiency. To create new kits that can be screened for phenotype, we have examined the development of the nervous system in embryos homozygous for more than 700 distinct deficiency mutations. A kit of ∼400 deficiency lines for which homozygotes have a recognizable nervous system and intact body walls encompasses >80% of the genome. Here we show examples of screens of this kit for orphan receptor ligands and neuronal antigen expression. It can also be used to find genes involved in expression, patterning, and subcellular localization of any protein that can be visualized by antibody staining. A subset kit of 233 deficiency lines, for which homozygotes develop relatively normally to late stage 16, covers ∼50% of the genome. We have screened it for axon guidance phenotypes, and we present examples of new phenotypes we have identified. The subset kit can be used to screen for phenotypes affecting all embryonic organs. In the future, these deficiency kits will allow Drosophila researchers to rapidly and efficiently execute genome-wide anatomical screens that require examination of individual embryos at high magnification

Myocardial Hypertrophy Overrides the Angiogenic Response to Hypoxia

Background: Cyanosis and myocardial hypertrophy frequently occur in combination. Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the expression of hypoxia-inducible factors (HIF), vascular endothelial growth factors (VEGF), and VEGF receptors (VEGFR-1 and 2); in contrast, pressure overload hypertrophy is often associated with impaired pro-angiogenic signaling and decreased myocardial capillary density. We hypothesized that the physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium is blunted through differential HIF and VEGF-associated signaling. Methods and Results: Newborn rabbits underwent aortic banding and, together with sham-operated littermates, were transferred into a hypoxic chamber (FiO2 = 0.12) at 3 weeks of age. Control banded or sham-operated rabbits were housed in normoxia. Systemic cyanosis was confirmed (hematocrit, arterial oxygen saturation, and serum erythropoietin). Myocardial tissue was assayed for low oxygen concentrations using a pimonidazole adduct. At 4 weeks of age, HIF-1α and HIF-2α protein levels, HIF-1α DNA-binding activity, and expression of VEGFR-1, VEGFR-2, and VEGF were determined in hypoxic and normoxic rabbits. At 6 weeks of age, left-ventricular capillary density was assessed by immunohistochemistry. Under normoxia, capillary density was decreased in the banded rabbits compared to non-banded littermates. As expected, non-hypertrophied hearts responded to hypoxia with increased capillary density; however, banded hypoxic rabbits demonstrated no increase in angiogenesis. This blunted pro-angiogenic response to hypoxia in the hypertrophied myocardium was associated with lower HIF-2α and VEGFR-2 levels and increased HIF-1α activity and VEGFR-1 expression. In contrast, non-hypertrophied hearts responded to hypoxia with increased HIF-2α and VEGFR-2 expression with lower VEGFR-1 expression. Conclusion: The participation of HIF-2α and VEGFR-2 appear to be required for hypoxia-stimulated myocardial angiogenesis. In infant rabbit hearts with pressure overload hypertrophy, this pro-angiogenic response to hypoxia is effectively uncoupled, apparently in part due to altered HIF-mediated signaling and VEGFR subtype expression

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

Optical Dissection of Neural Circuits Responsible for Drosophila Larval Locomotion with Halorhodopsin

Halorhodopsin (NpHR), a light-driven microbial chloride pump, enables silencing of neuronal function with superb temporal and spatial resolution. Here, we generated a transgenic line of Drosophila that drives expression of NpHR under control of the Gal4/UAS system. Then, we used it to dissect the functional properties of neural circuits that regulate larval peristalsis, a continuous wave of muscular contraction from posterior to anterior segments. We first demonstrate the effectiveness of NpHR by showing that global and continuous NpHR-mediated optical inhibition of motor neurons or sensory feedback neurons induce the same behavioral responses in crawling larvae to those elicited when the function of these neurons are inhibited by Shibirets, namely complete paralyses or slowed locomotion, respectively. We then applied transient and/or focused light stimuli to inhibit the activity of motor neurons in a more temporally and spatially restricted manner and studied the effects of the optical inhibition on peristalsis. When a brief light stimulus (1–10 sec) was applied to a crawling larva, the wave of muscular contraction stopped transiently but resumed from the halted position when the light was turned off. Similarly, when a focused light stimulus was applied to inhibit motor neurons in one or a few segments which were about to be activated in a dissected larva undergoing fictive locomotion, the propagation of muscular constriction paused during the light stimulus but resumed from the halted position when the inhibition (>5 sec) was removed. These results suggest that (1) Firing of motor neurons at the forefront of the wave is required for the wave to proceed to more anterior segments, and (2) The information about the phase of the wave, namely which segment is active at a given time, can be memorized in the neural circuits for several seconds

Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns

Multi-model seascape genomics identifies distinct environmental drivers of selection among sympatric marine species

Background As global change and anthropogenic pressures continue to increase, conservation and management increasingly needs to consider species’ potential to adapt to novel environmental conditions. Therefore, it is imperative to characterise the main selective forces acting on ecosystems, and how these may influence the evolutionary potential of populations and species. Using a multi-model seascape genomics approach, we compare putative environmental drivers of selection in three sympatric southern African marine invertebrates with contrasting ecology and life histories: Cape urchin (Parechinus angulosus), Common shore crab (Cyclograpsus punctatus), and Granular limpet (Scutellastra granularis). Results Using pooled (Pool-seq), restriction-site associated DNA sequencing (RAD-seq), and seven outlier detection methods, we characterise genomic variation between populations along a strong biogeographical gradient. Of the three species, only S. granularis showed significant isolation-by-distance, and isolation-by-environment driven by sea surface temperatures (SST). In contrast, sea surface salinity (SSS) and range in air temperature correlated more strongly with genomic variation in C. punctatus and P. angulosus. Differences were also found in genomic structuring between the three species, with outlier loci contributing to two clusters in the East and West Coasts for S. granularis and P. angulosus, but not for C. punctatus. Conclusion The findings illustrate distinct evolutionary potential across species, suggesting that species-specific habitat requirements and responses to environmental stresses may be better predictors of evolutionary patterns than the strong environmental gradients within the region. We also found large discrepancies between outlier detection methodologies, and thus offer a novel multi-model approach to identifying the principal environmental selection forces acting on species. Overall, this work highlights how adding a comparative approach to seascape genomics (both with multiple models and species) can elucidate the intricate evolutionary responses of ecosystems to global change