Loss of Intralipid?- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

Background

Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.

Methods

Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.

Results

Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.

Conclusions

Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.     

The Collective Action Problem but Not Numerical Superiority Explains Success in Intergroup Encounters in Verreaux’s Sifaka (Propithecus verreauxi): Implications for Individual Participation and Free-Riding

International Journal of Primatology - Socioecological theory predicts that larger groups are able to gain better access to resources because of their numerical advantage in intergroup contests....     

microRNA deregulation in keloids: an opportunity for clinical intervention?

Keloids are defined as benign dermal scars invading adjacent healthy tissue, characterized by aberrant fibroblast dynamics and overproduction of extracellular matrix. However, the aetiology and molecular mechanism of keloid production remain poorly understood. Recent discoveries have shed new light on the involvement of a class of non‐coding RNAs known as microRNAs (miRNA), in keloid formation. A number of miRNAs have differential expression in keloid tissues and keloid‐derived fibroblasts. These miRNAs have been characterized as novel regulators of cellular processes pertinent to wound healing, including extracellular matrix deposition and fibroblast proliferation. Delineating the functional significance of miRNA deregulation may help us better understand pathogenesis of keloids, and promote development of miRNA‐directed therapeutics against this condition.     

Abnormal cervical smears: are we in for an epidemic?

A retrospective study was conducted to examine the pattern of a disturbing increase in abnormal cervical smears in one health district. Past records over fifteen years (1965-79) were analysed to produce pick up rates according to age, screening state, severity of lesion, and area of residence. Main findings included an increased pick up rate in unscreened (5.8 to 12.9/1000 smears) and screened (0.9 to 3.6/1000 smears) women. The order of increase was proportionately much higher in women under 40 years. The only significant epidemiological variable in the catchment area was a substantial population increase, overweighted by the younger age groups. The principal conclusion of the study was that the increased pick up rates of abnormal cervical smears in the district reflected a true increase in the incidence of premalignant lesions of the cervix. Screening efforts aided by computerisation should be examined nationwide in order to reach high risk groups and thus try to prevent an increase in carcinoma of the cervix.     

Learning and Memory in Juvenile Zebrafish: What makes the Difference – Population or Rearing Environment?

The ability to learn and remember about the surrounding environment is crucial for the survival of organisms in their natural habitats. Adults of numerous fish species have been shown to display sophisticated behaviour related to learning and memory. This study deals with testing learning abilities among juveniles (10 wks old) of zebrafish (Danio rerio) through a simple task of finding food. We compared the performance of juveniles from two populations, a wild collected from a natural habitat and an aquarium‐bred purchased from a pet shop, reared in bare environment (lacking visual cues). Additionally, we also tested the effect of early habitat enrichment on the performance among juveniles of the aquarium‐bred population. The experiments involved training fishes to solve a simple maze (with a food reward at the end) and testing their memory. Learning was measured based on the time taken to complete the task (performance time) of finding food in the maze‐arena across repeated trials. Our results showed that juveniles from the two populations possessed significantly different learning abilities. There were population differences in exploratory tendency and time taken to accomplish the task. However, when memory was tested based on performance time between training and test day, individuals (from both populations) were found to be poor at memorizing learnt tasks. On the other hand, juveniles (belonging to aquarium‐bred population) reared in spatially complex environments displayed higher rates of learning and were capable of remembering learnt tasks better than their counterparts from bare environments. This study thus demonstrates the importance of rearing conditions and natural ecology in ontogenetic development of learning and memory functions among zebrafish.     

SHRSP/Izm and WKY/NCrlCrlj Rats Having a Missense Mutation in Abcg5 Deposited Plant Sterols in the Body,but Did Not Change Their Biliary Secretion and Lymphatic Absorption—Comparison with Jcl:Wistar and WKY/Izm Rats

We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols.     

Meeting report of the OECD conference on “Genome Editing: Applications in Agriculture—Implications for Health,Environment and Regulation”

Transgenic Research - The “OECD Conference on Genome Editing: Applications in Agriculture—Implications for Health, Environment and Regulation” was held on the 28–29 June...     

Reactive oxygen species and melanoma: an explanation for gender differences in survival?

Epidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti-oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS-resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti-oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival.     

Do Male and Female Cowbirds See Their World Differently? Implications for Sex Differences in the Sensory System of an Avian Brood Parasite

Background

Male and female avian brood parasites are subject to different selection pressures: males compete for mates but do not provide parental care or territories and only females locate hosts to lay eggs. This sex difference may affect brain architecture in some avian brood parasites, but relatively little is known about their sensory systems and behaviors used to obtain sensory information. Our goal was to study the visual resolution and visual information gathering behavior (i.e., scanning) of brown-headed cowbirds.

Methodology/Principal Findings

We measured the density of single cone photoreceptors, associated with chromatic vision, and double cone photoreceptors, associated with motion detection and achromatic vision. We also measured head movement rates, as indicators of visual information gathering behavior, when exposed to an object. We found that females had significantly lower density of single and double cones than males around the fovea and in the periphery of the retina. Additionally, females had significantly higher head-movement rates than males.

Conclusions

Overall, we suggest that female cowbirds have lower chromatic and achromatic visual resolution than males (without sex differences in visual contrast perception). Females might compensate for the lower visual resolution by gazing alternatively with both foveae in quicker succession than males, increasing their head movement rates. However, other physiological factors may have influenced the behavioral differences observed. Our results bring up relevant questions about the sensory basis of sex differences in behavior. One possibility is that female and male cowbirds differentially allocate costly sensory resources, as a recent study found that females actually have greater auditory resolution than males.     

Multiple Independent Introductions of HIV-1 CRF01_AE Identified in China: What Are the Implications for Prevention?

Background

HIV-1 CRF01_AE accounts for an important fraction of HIV infections in Asia including China, but little is known about the phylogenetic and evolutionary history of this CRF (circulating recombinant form). In the current study, we collected a large number of 1,957 CRF01_AE gag p17 sequences with known sampling year (1990-2010) from 5 global regions representing 15 countries to better understand the phylogenetic relationships and epidemic history of CRF01_AE strains in China.

Methodology/Principal Findings

CRF01_AE gag p17 sequences were retrieved from public databases to explore phylogenetic relationships and phylogeographic dynamics of CRF01_AE in Asia by using maximum-likelihood phylogenetics and Bayesian coalescent-based analyses. We found close phylogenetic relationships between sequences from Thailand, Vietnam and China. Moreover, at least 5 independent introductions and 5 independent autochthonous clades of CRF01_AE, which descended from Thailand or Vietnam were identified in China from 1991 through 2003.

Conclusion/Significance

The current study not only defines the migration of CRF01_AE clades to/in Asia, but also demonstrates the criticalness of identifying the circulating strains in the population for the development of vaccine and microbicides.     

Biliverdin reductase-A impairment links brain insulin resistance with increased Aβ production in an animal model of aging: Implications for Alzheimer disease

Brain insulin resistance is associated with an increased Aβ production in AD although the molecular mechanisms underlying this link are still largely unknown. Biliverdin reductase-A (BVR-A) is a unique Ser/Thr/Tyr kinase regulating insulin signalling. Studies from our group, demonstrated that BVR-A impairment is among the earliest events favoring brain insulin resistance development. Furthermore, reported a negative association between BVR-A protein levels/activation and BACE1 protein levels in the parietal cortex of aged beagles (an animal model of AD), thus suggesting a possible interaction. Therefore, we aimed to demonstrate that BVR-A impairment is a molecular bridge linking brain insulin resistance with increased Aβ production. Age-associated changes of BVR-A, BACE1, insulin signalling cascade and APP processing were evaluated in the parietal cortex of beagles and experiments to confirm the hypothesized mechanism(s) have been performed in vitro in HEK293APPswe cells. Our results show that BVR-A impairment occurs early with age and is associated with brain insulin resistance. Furthermore, we demonstrate that BVR-A impairment favors CK1-mediated Ser phosphorylation of BACE1 (known to mediate BACE1 recycling to plasma membrane) along with increased Aβ production in the parietal cortex, with age. Overall, our results suggest that the impairment of BVR-A is an early molecular event contributing to both (I) the onset of brain insulin resistance and (II) the increased Aβ production observed in AD. We, therefore, suggest that by targeting BVR-A activity it could be possible to delay the onset of brain insulin resistance along with an improved regulation of the APP processing.     

Models for truth‐telling in physician‐patient encounters: What can we learn from Yoruba concept of Ooto?

Empirical studies have now established that many patients make clinical decisions based on models other than Anglo American model of truth‐telling and patient autonomy. Some scholars also add that current medical ethics frameworks and recent proposals for enhancing communication in health professional‐patient relationship have not adequately accommodated these models. In certain clinical contexts where health professional and patients are motivated by significant cultural and religious values, these current frameworks cannot prevent communication breakdown, which can, in turn, jeopardize patient care, cause undue distress to a patient in certain clinical contexts or negatively impact his/her relationship with the community. These empirical studies have now recommended that additional frameworks developed around other models of truth‐telling; and which take very seriously significant value‐differences which sometimes exist between health professional and patients, as well as patient's cultural/religious values or relational capacities, must be developed. This paper contributes towards the development of one. Specifically, this study proposes a framework for truth‐telling developed around African model of truth‐telling by drawing insights from the communitarian concept of oot?? amongst the Yoruba people of south west Nigeria. I am optimistic that if this model is incorporated into current medical ethics codes and curricula, it will significantly enhance health professional‐patient communication.     

Persistence of the threatened Knysna warbler Bradypterus sylvaticus in an urban landscape: do gardens substitute for fire?

Food resources can limit populations of insectivorous birds. Previous studies have shown strong correlations between bird population densities and their invertebrate food, with declining populations being attributed to loss of prey. This might also be the case for the threatened Knysna warbler (Bradypterus sylvaticus), which in the last 20 years has declined precipitously on the Cape Peninsula, South Africa. The bird is abandoning natural, protected forests, retreating to narrow belts of suburban, riverine woodland with dense, tangled understoreys. The potential invertebrate food availability in natural forests and suburban woodland was assessed against what is known of the bird’s preferred prey. The invertebrate food resource spectrum and abundance were determined using three sampling techniques in both natural forest and suburban woodland. Despite greater overall abundance of invertebrates in suburban woodland, the warbler’s preferred prey items were equally abundant in both habitats. This suggests that reduced food supply does not explain abandonment of natural forests by the warbler. Rather, it is concluded that the availability of suitable nesting substrata, which are more abundant in suburban woodland, has driven the biotope shift. This is an unusual case of a localized and threatened bird species faring better under transformed conditions than in natural habitats.