The relevance of non-human primate and rodent malaria models for humans

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.     

Pannexin channels are not gap junction hemichannels

Pannexins, a class of membrane channels, bear significant sequence homology with the invertebrate gap junction proteins, innexins and more distant similarities in their membrane topologies and pharmacological sensitivities with the gap junction proteins, connexins. However, the functional role for the pannexin oligomers, or pannexons, is different from connexin oligomers, the connexons. Many pannexin publications have used the term "hemichannels" to describe pannexin oligomers while others use the term "channels" instead. This has led to confusion within the literature about the function of pannexins that promotes the idea that pannexons serve as gap junction hemichannels and thus have an assembly and functional state as gap junctional intercellular channels. Here we present the case that unlike the connexin gap junction intercellular channels, so far, pannexin oligomers have repeatedly been shown to be channels that are functional in single membranes, but not as intercellular channel in appositional membranes. Hence, they should be referred to as channels and not hemichannels. Thus, we advocate that in the absence of firm evidence that pannexins form gap junctions, the use of the term "hemichannel" be discontinued within the pannexin literature.     

In vitro comparison of agar and microbroth dilution methods for determination of MICs for Mycoplasma hominis

Ten replicates of three Mycoplasma hominis strains were tested by microbroth and agar dilution against levofloxacin, moxifloxacin, gatifloxacin, erythromycin, tetracycline, and clindamycin. Both methods provide reproducible results. Agar dilution tends to yield higher MIC values for some drugs.     

Entrainment of the human circadian system by light

The periodic light-dark cycle is the dominant environmental synchronizer used by humans to entrain to the geophysical 24-h day. Entrainment is a fundamental property of circadian systems by which the period of the internal clock (tau) is synchronized to the period of the entraining stimuli (T cycle). An important aspect of entrainment in humans is the maintenance of an appropriate phase relationship between the circadian system, the timing of sleep and wakefulness, and environmental time (a.k.a. the phase angle of entrainment) to maintain wakefulness throughout the day and consolidated sleep at night. In this article, we review these concepts and the methods for assessing circadian phase and period in humans, as well as discuss findings on the phase angle of entrainment in healthy adults. We review findings from studies that examine how the phase, intensity, duration, and spectral characteristics of light affect the response of the human biological clock and discuss studies on entrainment in humans, including recent studies of the minimum light intensity required for entrainment. We briefly review conditions and disorders in which failure of entrainment occurs. We provide an integrated perspective on circadian entrainment in humans with respect to recent advances in our knowledge of circadian period and of the effects of light on the biological clock in humans.     

Differences between Belclare and Suffolk ewes in fertilization rate, embryo quality and accessory sperm number after cervical or laparoscopic artificial insemination

Ewe breed has been shown to have a major effect on pregnancy rates following cervical AI using frozen-thawed semen. The main objective of this study was to examine the differences between purebred Belclare and Suffolk ewes (multiparous) in fertilization rate, number of accessory sperm and stage of embryo development on day 6 after cervical or laparoscopic AI with frozen-thawed semen. In experiment 1, Belclare and Suffolk ewes were synchronized for 12 days and were either cervically inseminated (year 1: n=28 and 31; year 2: n=16 and 15, respectively) or laparoscopically inseminated (year 2: n=13 and 14). In experiment 2, superovulated Belclare (n=4) and Suffolk (n=13) ewes were laparoscopically inseminated. All ewes were slaughtered 6 days after AI; oocytes/embryos were recovered, morphologically graded and stained to assess the number of cells and accessory spermatozoa. Data from both experiments were combined for statistical analysis. The proportion of ewes with fertilized oocytes was significantly higher following laparoscopic AI compared with cervical AI (54% versus 19%). More Belclare than Suffolk ewes yielded fertilized oocyte(s) after cervical AI (34% versus 10%, P<0.02) but there was no difference after laparoscopic AI (62% versus 60%). From the ewes that yielded at least one fertilized oocyte the proportion of Belclare ewes with embryos at the morula/blastocyst stage was significantly greater than for Suffolk ewes (94% versus 59%, P<0.02). A higher proportion of Belclare than Suffolk ewes had evidence of sperm reaching the site of fertilization following cervical AI (39% versus 15%, P<0.02) but there was no difference after laparoscopic AI (62% versus 64%, P>0.8). Amongst the ewes with evidence of sperm at the site of fertilization, laparoscopic AI resulted in a higher number of sperm per oocyte/embryo or per ewe than cervical AI (P<0.01). These results suggested that the difference in pregnancy rate between Suffolk and Belclare ewes following cervical AI was due to: (i) sperm traversing the cervix and uterus in a higher proportion of Belclare than Suffolk ewes, leading to a higher incidence of fertilization and (ii) the lower developmental competence of fertilized oocytes from Suffolk ewes.     

Molecular and morphological evolution of the amphipod radiation of Lake Baikal

Lake Baikal, in Siberia, Russia, contains the highest biodiversity of any extant lake, including an impressive radiation of gammaroidean amphipods that are often cited as a classic case of adaptive radiation. However, relationships among Baikal's amphipods remain poorly understood. The phylogenetic history of 32 Lake Baikal amphipod species, representing most major lineages of the endemic fauna, was examined using three genes (COI, 16S rRNA, and 18S rRNA), and 152 morphological characters. Results support monophyly of the largest and most diverse of the Baikalian families, the Acanthogammaridae. Analyses suggest that a second Baikalian family, the fossorial Micruropodidae, is paraphyletic and composed of two divergent clades, one of which includes Macrohectopus branickii, a morphologically specialized pelagic planktivore traditionally assigned its own family. The extreme morphological and ecological divergence of Macrohectopus from its close genetic relatives, and conversely, the large genetic distances among other morphologically similar micruropodids, suggest that morphological and molecular evolution have often been uncoupled during the radiation of Baikal's amphipods. This study suggests that the amphipod fauna of Lake Baikal is polyphyletic; originating from two independent invasions of the lake.     

Cyclic urea derivatives as potent NK1 selective antagonists

A series of novel five- and six-membered ring urea derivatives have been described as potent and selective NK1 receptor antagonists. Several compounds in this series exhibited good oral activity and brain penetration. Syntheses of these compounds are also described herein.     

A computational investigation of kinetoplastid trans-splicing

Trans-splicing is an unusual process in which two separate RNA strands are spliced together to yield a mature mRNA. We present a novel computational approach which has an overall accuracy of 82% and can predict 92% of known trans-splicing sites. We have applied our method to chromosomes 1 and 3 of Leishmania major, with high-confidence predictions for 85% and 88% of annotated genes respectively. We suggest some extensions of our method to other systems.     

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts

Background  

Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction.     

Don't lose heart--therapeutic value of apoptosis prevention in the treatment of cardiovascular disease

Cardiovascular disease is a leading cause of death worldwide. Loss of function or death of cardiomyocytes is a major contributing factor to these diseases. Cell death in conditions such as heart failure and myocardial infarction is associated with apoptosis. Apoptotic pathways have been well studied in non-myocytes and it is thought that similar pathways exist in cardiomyocytes. These pathways include death initiated by ligation of membrane-bound death receptors, release of pro-apoptotic factors from mitochondria or stress at the endoplasmic reticulum. The key regulators of apoptosis include inhibitors of caspases (IAPs), the Bcl-2 family of proteins, growth factors, stress proteins, calcium and oxidants. The highly organized and predictive nature of apoptotic signaling means it is amenable to manipulation. A thorough understanding of the apoptotic process would facilitate intervention at the most suitable points, alleviating myocardium decline and dysfunction. This review summarizes the mechanisms underlying apoptosis and the mediators/regulators involved in these signaling pathways. We also discuss how the potential therapeutic value of these molecules could be harnessed.