Effect of hyperthermia on blood constituents in the domestic rabbit (Lepus cuniculus)

1. 1. Effects of exposing rabbits to temperatures 37–50°C on body-core temperature and some blood constituents were investigated.

2. 2. Heat stroke death occurred at or above a critical core-temperature of 43.0°C.

3. 3. Plasma osmolality and levels of glucose, urea and lactate were significantly elevated in hyperthermia.

4. 4. Widespread tissue damage was indicated by increases in plasma activities of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and creatinine phosphokinase (CPK).

5. 5. The most sensitive indicators of impending heat stroke in heat stressed rabbits were plasma levels or urea, lactate and CPK.

β-Cyclodextrin polymer nanoparticles as carriers for doxorubicin and artemisinin: a spectroscopic and photophysical study

The association of doxorubicin (DOX) and artemisinin (ART) to a β-CyD-epichlorohydrin crosslinked polymer (pβ-CyD), organized in nanoparticles of ca. 15 nm size, was investigated in neutral aqueous medium by circular dichroism (CD), UV-vis absorption and fluorescence. The stability constants and the absolute CD spectra of the drug complexes were determined by global analysis of multiwavelength data from spectroscopic titrations. The polymer pβ-CyD proved able to disrupt the DOX dimer when the latter is the predominant form of DOX in solution. The spectroscopic and photophysical properties of the complexes evidenced an alcohol-like environment for ART and an improved inherent emission ability for DOX in the nanoparticle frame.     

Acquisition of HIV by African-Born Residents of Victoria,Australia: Insights from Molecular Epidemiology

African-born Australians are a recognised “priority population” in Australia''s Sixth National HIV/AIDS Strategy. We compared exposure location and route for African-born people living with HIV (PLHIV) in Victoria, Australia, with HIV-1 pol subtype from drug resistance assays and geographical origin suggested by phylogenetic analysis of env gene. Twenty adult HIV positive African-born Victorian residents were recruited via treating doctors. HIV exposure details were obtained from interviews and case notes. Viral RNA was extracted from participant stored plasma or whole blood. The env V3 region was sequenced and compared to globally representative reference HIV-1 sequences in the Los Alamos National Library HIV Database. Twelve participants reported exposure via heterosexual sex and two via iatrogenic blood exposures; four were men having sex with men (MSM); two were exposed via unknown routes. Eight participants reported exposure in their countries of birth, seven in Australia, three in other countries and two in unknown locations. Genotype results (pol) were available for ten participants. HIV env amplification was successful in eighteen cases. HIV-1 subtype was identified in all participants: eight both pol and env; ten env alone and two pol alone. Twelve were subtype C, four subtype B, three subtype A and one subtype CRF02_AG. Reported exposure location was consistent with the phylogenetic clustering of env sequences. African Australians are members of multiple transnational social and sexual networks influencing their exposure to HIV. Phylogenetic analysis may complement traditional surveillance to discern patterns of HIV exposure, providing focus for HIV prevention programs in mobile populations.     

Colour constancy in insects

Colour constancy is the perceptual phenomenon that the colour of an object appears largely unchanged, even if the spectral composition of the illuminating light changes. Colour constancy has been found in all insect species so far tested. Especially the pollinating insects offer a remarkable opportunity to study the ecological significance of colour constancy since they spend much of their adult lives identifying and choosing between colour targets (flowers) under continuously changing ambient lighting conditions. In bees, whose colour vision is best studied among the insects, the compensation provided by colour constancy is only partial and its efficiency depends on the area of colour space. There is no evidence for complete ‘discounting’ of the illuminant in bees, and the spectral composition of the light can itself be used as adaptive information. In patchy illumination, bees adjust their spatial foraging to minimise transitions between variously illuminated zones. Modelling allows the quantification of the adaptive benefits of various colour constancy mechanisms in the economy of nature. We also discuss the neural mechanisms and cognitive operations that might underpin colour constancy in insects.     

Nanobody‐mediated resistance to Grapevine fanleaf virus in plants

Since their discovery, single‐domain antigen‐binding fragments of camelid‐derived heavy‐chain‐only antibodies, also known as nanobodies (Nbs), have proven to be of outstanding interest as therapeutics against human diseases and pathogens including viruses, but their use against phytopathogens remains limited. Many plant viruses including Grapevine fanleaf virus (GFLV), a nematode‐transmitted icosahedral virus and causal agent of fanleaf degenerative disease, have worldwide distribution and huge burden on crop yields representing billions of US dollars of losses annually, yet solutions to combat these viruses are often limited or inefficient. Here, we identified a Nb specific to GFLV that confers strong resistance to GFLV upon stable expression in the model plant Nicotiana benthamiana and also in grapevine rootstock, the natural host of the virus. We showed that resistance was effective against a broad range of GFLV isolates independently of the inoculation method including upon nematode transmission but not against its close relative, Arabis mosaic virus. We also demonstrated that virus neutralization occurs at an early step of the virus life cycle, prior to cell‐to‐cell movement. Our findings will not only be instrumental to confer resistance to GFLV in grapevine, but more generally they pave the way for the generation of novel antiviral strategies in plants based on Nbs.     

Carnitine and acylcarnitine profiles in dried blood spots of patients with acute myocardial infarction

Earlier studies have suggested an important role of carnitine pathway in cardiovascular pathology. However, the redistribution of carnitine and acylcarnitine pools, as a result of altered carnitine metabolism, is not clearly known in patients with acute myocardial infarction (AMI). We compared the carnitine and acylcarnitine profiles of 65 AMI patients, including 26 ST-elevated myocardial infarction (STEMI) and 39 non-ST-elevated myocardial infarction (NSTEMI), 28 patients with chest pain and 154 normal controls. The levels of carnitine and acylcarnitines in the blood spots were determined using LC-MS/MS. Total and free carnitine levels were significantly higher in all the patient groups in the following order: STEMI > NSTEMI > chest pain. The levels of short- and medium-chain acylcarnitines were significantly higher in patient groups. Among the long-chain acylcarnitines, C14:2 and C16:1 levels were significantly increased in STEMI and NSTEMI. The ratio of free carnitine to short-chain or medium-chain acylcarnitines was significantly decreased in STEMI, NSTEMI and chest pain patients however a significant increase was observed in the ratio of carnitine to long-chain acylcarnitines in all the patient groups as compared to normal controls. In conclusion, alterations in carnitine and acylcarnitine levels in the blood of AMI patients indicate the possibility of impaired carnitine homeostasis in ischemic myocardium. The clinical implications of these findings for the risk screening or diagnosis and prognosis of AMI require additional follow-up studies on large number of patients. We also suggest that a dual-marker strategy using carnitine (longer plasma half-life) in combination with troponin (shorter plasma half-life) could be a more promising biomarker strategy in risk stratification of patients.     

Salt effects on the growth, mineral nutrition, essential oil yield and composition of marjoram (Origanum majorana)

The aim of this work was to investigate the growth, mineral nutrition and essential oil composition of marjoram aerial part. Seedlings were cultivated for 20 days on nutrient solution, and then transferred to hydroponic solution with different NaCl concentrations (0, 50, 100, 150 mM). Plants were harvested after 17 days of treatment. Mineral nutrition and essential oil composition of shoots were determined. Results showed that growth, water content and development of the different organs of marjoram plant were affected just at the highest NaCl concentration (150 mM). Furthermore, salt did not seem to affect leaf area and root length but reduced the number of leaves. An increase in the total leaf surface and its thickness was observed at different NaCl concentrations. At 50 mM NaCl, sodium was primarily accumulated in roots but at 150 mM, it was strongly accumulated in leaves. However, Cl^? accumulation was lower at higher NaCl concentrations. Essential oil yield of marjoram shoots was 0.12% in the control and 0.10% at 50 mM but an important decrease was observed at 100 mM (0.05%). Thirty-three components were identified belonging to different chemical classes. In the control, the essential oil was found to be rich in trans-sabinene hydrate (47.67%), terpinen-4-ol (20.82%) and cis-sabinene hydrate (7.23%). The proportions of these main compounds were differently affected by salt.     

A Multivariate Genome-Wide Association Analysis of 10 LDL Subfractions,and Their Response to Statin Treatment,in 1868 Caucasians

We conducted a genome-wide association analysis of 7 subfractions of low density lipoproteins (LDLs) and 3 subfractions of intermediate density lipoproteins (IDLs) measured by gradient gel electrophoresis, and their response to statin treatment, in 1868 individuals of European ancestry from the Pharmacogenomics and Risk of Cardiovascular Disease study. Our analyses identified four previously-implicated loci (SORT1, APOE, LPA, and CETP) as containing variants that are very strongly associated with lipoprotein subfractions (log₁₀Bayes Factor > 15). Subsequent conditional analyses suggest that three of these (APOE, LPA and CETP) likely harbor multiple independently associated SNPs. Further, while different variants typically showed different characteristic patterns of association with combinations of subfractions, the two SNPs in CETP show strikingly similar patterns - both in our original data and in a replication cohort - consistent with a common underlying molecular mechanism. Notably, the CETP variants are very strongly associated with LDL subfractions, despite showing no association with total LDLs in our study, illustrating the potential value of the more detailed phenotypic measurements. In contrast with these strong subfraction associations, genetic association analysis of subfraction response to statins showed much weaker signals (none exceeding log₁₀Bayes Factor of 6). However, two SNPs (in APOE and LPA) previously-reported to be associated with LDL statin response do show some modest evidence for association in our data, and the subfraction response proles at the LPA SNP are consistent with the LPA association, with response likely being due primarily to resistance of Lp(a) particles to statin therapy. An additional important feature of our analysis is that, unlike most previous analyses of multiple related phenotypes, we analyzed the subfractions jointly, rather than one at a time. Comparisons of our multivariate analyses with standard univariate analyses demonstrate that multivariate analyses can substantially increase power to detect associations. Software implementing our multivariate analysis methods is available at http://stephenslab.uchicago.edu/software.html.