The effects of ATP and sodium chloride on the cytochrome c-cardiolipin interaction: the contrasting behavior of the horse heart and yeast proteins

In cells a portion of cytochrome c (cyt c) (15–20%) is tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane. The CL-bound protein, which has nonnative tertiary structure, altered heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in the apoptotic process. This has attracted considerable interest in order to clarify the mechanisms governing the cyt c–CL interaction. Herein we have investigated the binding reaction of CL with the c-type cytochromes from horse heart and yeast. Although the two proteins possess a similar tertiary architecture, yeast cyt c displays lower stability and, contrary to the equine protein, it does not bind ATP and lacks pro-apoptotic activity. The study has been performed in the absence and in the presence of ATP and NaCl, two compounds that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic activity of the protein. The two proteins behave differently: while CL interaction with horse cyt c is strongly influenced by the two effectors, no effect is observed for yeast cyt c. It is noteworthy that NaCl induces dissociation of the (horse cyt c)–CL complex but has no influence on that of yeast cyt c. The differences found for the two proteins highlight that specific structural factors, such as the different local structure conformation of the regions involved in the interactions with either CL or ATP, can significantly affect the behavior of cyt c in its reaction with liposomes and the subsequent pro-apoptotic action of the protein.     

Sleeping site selection and presleep behavior in wild pigtailed macaques

Several factors are likely to control sleeping site selection and presleep behavior in nonhuman primates, including predation risk and location of food resources. We examined the effects of these factors on the sleeping behavior of northern pigtailed macaques (Macaca leonina). While following a troop living in the surroundings of the Visitor Center of Khao Yai National Park (Thailand), we recorded the physical characteristics and location of each sleeping site, tree, the individuals' place in the tree, posture, and behavior. We collected data for 154 nights between April 2009 and November 2010. The monkeys preferred tall sleeping trees (20.9 ± SD 4.9 m) and high sleeping places (15.8 ± SD 4.3 m), which may be an antipredator strategy. The choice of sleeping trees close to the last (146.7 ± SD 167.9 m) or to the first (150.4 ± SD 113.0 m) feeding tree of the day may save energy and decrease predation risk when monkeys are searching for food. Similarly, the choice of sleeping sites close to human settlements eases the access to human food during periods of fruit scarcity. Finally, the temporal pattern of use of sleeping sites, with a preference for four of the sleeping sites but few reuses during consecutive nights, may be a trade‐off between the need to have several sleeping sites (decreasing detection by predators and travel costs to feeding sites), and the need to sleep in well‐known sites (guaranteeing a faster escape in case of predator attack). Am. J. Primatol. 73:1222–1230, 2011. © 2011 Wiley Periodicals, Inc.     

Ecological Niche Modelling of Potential West Nile Virus Vector Mosquito Species and Their Geographical Association with Equine Epizootics in Italy

In Italy, West Nile virus (WNV) equine outbreaks have occurred annually since 2008. Characterizing WNV vector habitat requirements allows for the identification of areas at risk of viral amplification and transmission. Maxent-based ecological niche models were developed using literature records of 13 potential WNV Italian vector mosquito species to predict their habitat suitability range and to investigate possible geographical associations with WNV equine outbreak occurrence in Italy from 2008 to 2010. The contribution of different environmental variables to the niche models was also assessed. Suitable habitats for Culex pipiens, Aedes albopictus, and Anopheles maculipennis were widely distributed; Culex modestus, Ochlerotatus geniculatus, Ochlerotatus caspius, Coquillettidia richiardii, Aedes vexans, and Anopheles plumbeus were concentrated in north-central Italy; Aedes cinereus, Culex theileri, Ochlerotatus dorsalis, and Culiseta longiareolata were restricted to coastal/southern areas. Elevation, temperature, and precipitation variables showed the highest predictive power. Host population and landscape variables provided minor contributions. WNV equine outbreaks had a significantly higher probability to occur in habitats suitable for Cx. modestus and Cx. pipiens, providing circumstantial evidence that the potential distribution of these two species coincides geographically with the observed distribution of the disease in equines.     

Comparing the Device Physics and Morphology of Polymer Solar Cells Employing Fullerenes and Non‐Fullerene Acceptors

There is a need to find electron acceptors for organic photovoltaics that are not based on fullerene derivatives since fullerenes have a small band gap that limits the open‐circuit voltage (V_OC), do not absorb strongly and are expensive. Here, a phenylimide‐based acceptor molecule, 4,7‐bis(4‐(N‐hexyl‐phthalimide)vinyl)benzo[c]1,2,5‐thiadiazole (HPI‐BT), that can be used to make solar cells with V_OC values up to 1.11 V and power conversion efficiencies up to 3.7% with two thiophene polymers is demonstrated. An internal quantum efficiency of 56%, compared to 75–90% for polymer‐fullerene devices, results from less efficient separation of geminate charge pairs. While favorable energetic offsets in the polymer‐fullerene devices due to the formation of a disordered mixed phase are thought to improve charge separation, the low miscibility (<5 wt%) of HPI‐BT in polymers is hypothesized to prevent the mixed phase and energetic offsets from forming, thus reducing the driving force for charges to separate into the pure donor and acceptor phases where they can be collected.     

Influence of Sampling on the Determination of Warfarin and Warfarin Alcohols in Oral Fluid

Background and Objective

The determination of warfarin, RS/SR- and RR/SS-warfarin alcohols in oral fluid may offer additional information to the INR assay. This study aimed to establish an optimized sampling technique providing the best correlation between the oral fluid and the unbound plasma concentrations of these compounds.

Materials and Methods

Samples of non-stimulated and stimulated oral fluid, and blood were collected from 14 patients undergoing warfarin therapy. After acidification, analytes were extracted with a dichloromethane/hexane mixture and determined by HPLC with fluorescence detection. Plasma samples were also ultrafiltered for the determination of the unbound fraction. The chromatographic separation was carried out in isocratic conditions with a phosphate buffer/methanol mobile phase on a C-18 reversed-phase column. The absence of interfering compounds was verified by HPLC-ESI-Q-TOF.

Results

Stimulation generally increased the oral fluid pH to values close to blood pH in about 6 minutes. The concentration of warfarin and RS/SR-warfarin alcohols in oral fluid followed the same trend, whereas the concentration of RR/SS-warfarin alcohols was not affected. Six minute stimulation with chewing gum followed by collection with a polyester swab was the best sampling procedure, with a good repeatability (RSD <10%) and relatively low inter-subject variability (RSD  = 30%) of the oral fluid to plasma ratio. This procedure provided strong correlations between the measured oral fluid and unbound plasma concentration of warfarin (r  =  0.92, p <0.001) and RS/SR-warfarin alcohols (r  =  0.84, p <0.001), as well as between stimulated oral fluid and total plasma concentration of warfarin (r  =  0.78, p <0.001) and RS/SR-warfarin alcohols (r  =  0.81, p <0.001).

Conclusion

The very good correlation between oral fluid and unbound plasma concentration of warfarin and RS/SR-warfarin alcohols suggests that oral fluid analysis could provide clinically useful information for the monitoring of anticoagulant therapy, complementary to the INR assay.     

Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior in females but not males and protection from neurological deficits during proestrus

Background

Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is one of the most prevalent neurological disorders in the industrialized world. This disease afflicts more than two million people worldwide, over two thirds of which are women. MS is typically diagnosed between the ages of 20–40 and can produce debilitating neurological impairments including muscle spasticity, muscle paralysis, and chronic pain. Despite the large sex disparity in MS prevalence, clinical and basic research investigations of how sex and estrous cycle impact development, duration, and severity of neurological impairments and pain symptoms are limited. To help address these questions, we evaluated behavioral signs of sensory and motor functions in one of the most widely characterized animal models of MS, the experimental autoimmune encephalomyelitis (EAE) model.

Methods

C57BL/6 male and female mice received flank injection of complete Freund’s adjuvant (CFA) or CFA plus myelin oligodendrocyte glycoprotein 35-55 (MOG_35-55) to induce EAE. Experiment 1 evaluated sex differences of EAE-induced neurological motor deficits and neuropathic pain-like behavior over 3 weeks, while experiment 2 evaluated the effect of estrous phase in female mice on the same behavioral measures for 3 months. EAE-induced neurological motor deficits including gait analysis and forelimb grip strength were assessed. Neuropathic pain-like behaviors evaluated included sensitivity to mechanical, cold, and heat stimulations. Estrous cycle was determined daily via vaginal lavage.

Results

MOG_35-55-induced EAE produced neurological impairments (i.e., motor dysfunction) including mild paralysis and decreases in grip strength in both females and males. MOG_35-55 produced behavioral signs of neuropathic pain—mechanical and cold hypersensitivity—in females, but not males. MOG_35-55 did not change cutaneous heat sensitivity in either sex. Administration of CFA or CFA?+?MOG_35-55 prolonged the time spent in diestrus for 2 weeks, after which normal cycling returned. MOG_35-55 produced fewer neurological motor deficits when mice were in proestrus relative to non-proestrus phases.

Conclusions

We conclude that female mice are superior to males for the study of neuropathic pain-like behaviors associated with MOG_35-55-induced EAE. Further, proestrus may be protective against EAE-induced neurological deficits, thus necessitating further investigation into the impact that estrous cycle exerts on MS symptoms.

     

Past cover modulates the intense and spatially structured natural regeneration of woody vegetation in a pastureland

Plant Ecology - Vegetation natural regeneration after agricultural abandonment is changing the landscape patterns in many areas worldwide. However, the expansion rate, spatio-temporal dynamics, and...     

Inferring species abundance distribution across spatial scales

A long-standing problem in ecology is to understand how the species–abundance distribution (SAD) varies with sampling scale. The problem was first characterized by Preston as the veil line problem. Although theoretical and empirical studies have now shown the nonexistence of the veil line, this problem has generated much interest in scaling biodiversity patterns. However, research on scaling SAD has so far exclusively focused on the relationship between the SAD in a smaller sampling area and a known SAD assumed for a larger area. An unsolved challenge is how one may predict species–abundance distribution in a large area from that of a smaller area. Although upscaling biodiversity patterns (e.g. species–area curve) is a major focus of macroecological research, upscaling of SAD across scale is, with few exceptions, ignored in the literature. Methods that directly predict SAD in a larger area from that of a smaller area have just started being developed. Here we propose a Bayesian method that directly answers this question. Examples using empirical data from tropical forests of Malaysia and Panama are employed to demonstrate the use of the method and to examine its performance with increasing sampling area. The results indicate that only 10-15% of the total census area is needed to adequately predict species abundance distribution of a region. In addition to species abundance distributions, the method also predicts well the regional species richness.