Platelets present antigen in the context of MHC class I

Platelets are most recognized for their vital role as the cellular mediator of thrombosis, but platelets also have important immune functions. Platelets initiate and sustain vascular inflammation in many disease conditions, including arthritis, atherosclerosis, transplant rejection, and severe malaria. We now demonstrate that platelets express T cell costimulatory molecules, process and present Ag in MHC class I, and directly activate naive T cells in a platelet MHC class I-dependent manner. Using an experimental cerebral malaria mouse model, we also demonstrate that platelets present pathogen-derived Ag to promote T cell responses in vivo, and that platelets can be used in a cell-based vaccine model to induce protective immune responses. Our study demonstrates a novel Ag presentation role for platelets.     

Gorgorhynchoides pseudocarangis n. sp. (Acanthocephala: Isthmosacanthidae) from Pseudocaranx dentex (Carangidae) in southeast Queensland,Australia, with comments on the Isthmosacanthidae

Gorgorhynchoides pseudocarangis n. sp. (Isthmosacanthidae), is described from the intestine of the white trevally Pseudocaranx dentex (Bloch & Schneider) (Carangiformes: Carangidae) collected in Moreton Bay, Queensland, Australia. The new species has a proboscis armature of 27–28 rows of 16–17 hooks. It is most similar morphologically to Gorgorhynchoides bullocki Cable & Marafachisi, 1970 and Gorgorhynchoides gnathanodontos Smales, 2014 but differs from the former in having a longer proboscis with more rows of hooks, ventral hooks 6/7–12 with notched tips and trunk spines which do not extend onto the anterior bulbous swelling, and from the latter in having a longer proboscis, ventral hooks 6/7–12 with notched tips, more circles of trunk spines, larger eggs and a proboscis armature with all hooks lacking manubria. Previous molecular phylogenetic analyses have shown that the genus Serrasentis Van Cleave, 1923 is sister to Gorgorhynchoides Cable & Linderoth, 1963, although some have failed to resolve these two lineages in separate monophyletic clades. We performed novel single-gene and concatenated phylogenetic analyses using cox1 mtDNA, 18S and 28S rDNA gene-sequences, resolving Gorgorhynchoides and Serrasentis in monophyletic sister clades and demonstrating that Gorgorhynchoides pseudocarangis n. sp. is phylogenetically distinct from related species for which molecular sequence data are available. We view the previous amendment of the Isthmosacanthidae to include the genera Golvanorhynchus Noronha, Fabio & Pinto, 1987, Gorgorhynchoides, Isthmosacanthus Smales 2014 and Serrasentis, and the transfer of the family to the Polymorphida, as the most satisfactory classification at present, although additional molecular evidence would provide greater stability.

     

Three acoustic forms of Allen's galagos (Primates; Galagonidae) in the Central African region

This study identifies populations currently classified as Allen's galago (Galago alleni) at ten locations in Gabon, Cameroon and Bioko Island. Morphological diversity was evident both within and between populations. Attention to the loud calls revealed three distinct vocal profiles which are consistent within biogeographical regions. This work is based on the Recognition Concept of Species which refers to a Specific Mate Recognition System. Galagos rely less on visual signals than diurnal primates and recognise each other principally by means of auditory and olfactory signals. Galagos possess repertoires of loud calls relating to contact and alarm which are thought to be species-specific. Other studies of nocturnal prosimians (galagos, tarsiers) have demonstrated that the unique loud call repertoires are reliable indicators of species boundaries; whereas characters such as body size and pelage coloration are highly variable, even within populations. The vocal data in this study provide evidence of at least three acoustic forms of galago within the Allen's group which are predicted to represent three distinct species: the Allen's form on Bioko Island and south-west Cameroon, the Gabon form in southern Cameroon and northern Gabon and the Makandé form in Gabon south of the Ogooué river. Some populations may be vulnerable to extinction due to limited distributions and habitat destruction. Electronic Publication     

Componental analysis of the ocellar electroretinogram of the locust, Schistocerca gregaria

Ruck's componental analysis of the ocellar electroretinogram (ERG) has been reappraised using techniques of signal averaging and waveform subtraction. Components (1), (3), and (4) can readily be isolated in the locust ocellus but component (2) as recorded in the locust ocellus is probably an artefact. Component (1), produced by the receptor cells, only contributes significantly to the total ERG at higher light intensities and it is this contribution which changes most with the degree of light and dark adaptation employed in these experiments. Component (3), the response of the second-order neurones, indicates that the majority of second-order neurones hyperpolarize on illumination of the ocellus. Component (4), the afferent activity of the second-order cells, indicates that more than one afferent axon is involved in the production of off spikes in the locust ocellus.     

Nicotinic acid and DP1 blockade: studies in mouse models of atherosclerosis

The use of nicotinic acid to treat dyslipidemia is limited by induction of a “flushing” response, mediated in part by the interaction of prostaglandin D₂ (PGD₂) with its G-protein coupled receptor, DP1 (Ptgdr). The impact of DP1 blockade (genetic or pharmacologic) was assessed in experimental murine models of atherosclerosis. In Ptgdr^−/−ApoE^−/− mice versus ApoE^−/− mice, both fed a high-fat diet, aortic cholesterol content was modestly higher (1.3- to 1.5-fold, P < 0.05) in Ptgdr^−/−ApoE^−/− mice at 16 and 24 weeks of age, but not at 32 weeks. In multiple ApoE^−/− mouse studies, a DP1-specific antagonist, L-655, generally had a neutral to beneficial effect on aortic lipids in the presence or absence of nicotinic acid treatment. In a separate study, a modest increase in some atherosclerotic measures was observed with L-655 treatment in Ldlr^−/− mice fed a high-fat diet for 8 weeks; however, this effect was not sustained for 16 or 24 weeks. In the same study, treatment with nicotinic acid alone generally decreased plasma and/or aortic lipids, and addition of L-655 did not negate those beneficial effects. These studies demonstrate that inhibition of DP1, with or without nicotinic acid treatment, does not lead to consistent or sustained effects on plaque burden in mouse atherosclerotic models.     

Systematic segregation to mutant mitochondrial DNA and accompanying loss of mitochondrial DNA in human NT2 teratocarcinoma Cybrids

In this study a well-characterized pathological mutation at nucleotide position 3243 of human mitochondrial DNA was introduced into human rho(0) teratocarcinoma (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the mutation, mitotic segregation toward increasing levels of mutant mitochondrial DNA always occurred. Rapid segregation was frequently followed by complete loss of mitochondrial DNA. These findings support the idea that pathological mitochondrial DNA mutations are particularly deleterious in specific cell types, which can explain some of the tissue-specific aspects of mitochondrial DNA diseases. Moreover, these findings suggest that mitochondrial DNA depletion may be an important and widespread feature of mitochondrial DNA disease.     

An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration

Lecithin cholesterol acyltransferase (LCAT) plays a key role in the reverse cholesterol transport (RCT) process by converting cholesterol to cholesteryl ester to form mature HDL particles, which in turn deliver cholesterol back to the liver for excretion and catabolism. HDL levels in human plasma are negatively correlated with cardiovascular risk and HDL functions are believed to be more important in atheroprotection. This study investigates whether and how D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, influences LCAT activity in the completion of the RCT process. We demonstrated that the apparent rate constant value of the LCAT enzyme reaction gives a measure of LCAT activity and determined the effects of free metals and a reducing agent on LCAT activity, showing an inhibition hierarchy of Zn²⁺>Mg²⁺>Ca²⁺ and no inhibition with β-mercaptoethanol up to 10 mM. We reconstituted nano-disc particles using apoA-I or D-4F with phospholipids. These particles elicited good activity in vitro in the stimulation of cholesterol efflux from macrophages through the ATP-binding cassette transporter A1 (ABCA1). With these particles we studied the LCAT activity and demonstrated that D-4F did not activate LCAT in vitro. Furthermore, we have done in vivo experiments with apoE-null mice and demonstrated that D-4F (20 mg/kg body weight, once daily subcutaneously) increased LCAT activity and HDL level as well as apoA-I concentration at 72 hours post initial dosing. Finally, we have established a correlation between HDL concentration and LCAT activity in the D-4F treated mice.     

Cryopreservation of economically valuable marine micro-algae in the classes Bacillariophyceae, Chlorophyceae, Cyanophyceae, Dinophyceae, Haptophyceae, Prasinophyceae, and Rhodophyceae

The ability to routinely cryopreserve micro-algal species reduces costs associated with maintaining large culture collections and reduces the risks of losing particular strains or species through contamination and genetic drift. Cryopreservation is also a useful adjunct in aquaculture hatcheries for strains of micro-algae where the nutritional status may change as a result of continuous sub-culture. In this study, cryopreservation of isolates from seven micro-algal classes was investigated. Successful candidates included the marine dinoflagellates Amphidinium carterae, Amphidinium trulla, and Gymnodinium simplex, and the haptophytes Chrysochromulina simplex, Prymnesium parvum, Prymnesium parvum f. patelliferum, Isochrysis galbana, and Pavlova lutheri. Also successfully cryopreserved were the planktonic diatoms Chaetoceros calcitrans, Chaetoceros muelleri, Chaetoceros sp., and the benthic Nitzschia ovalis, the chlorophyte Chlamydomonas coccoides, the rhodophyte Porphyridium purpureum, the prasinophytes Tetraselmis chuii, and Tetraselmis suecica, and the cyanophytes Raphidiopsis sp., and Aphanizomenon flos-aquae. All species were successfully cryopreserved using 15% Me2SO.     

Lack of Interleukin-6 (IL-6) Enhances Susceptibility to Infection but Does Not Alter Latency or Reactivation of Herpes Simplex Virus Type 1 in IL-6 Knockout Mice

The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 10(5) PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 x 10(4) and 2.7 x 10(3) PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation.     

The extended relationship between child cardiovascular risks and academic performance measures

Objective: To examine the relationship between children's overweight status and other cardiovascular risk fitness factors and academic performance among fifth‐grade students. Research Methods and Procedures: Using a sample of 968 fifth‐grade students (50.7% boys; mean age = 10.6 years), children's cardiovascular risks (BMI, blood pressure, acanthosis nigricans) and fitness measures were compared with their mean group performance scores across four subscales (mathematics, reading/language arts, science, and social studies) of a statewide standardized academic performance test. Results: Of this sample, 39% were either at risk for being overweight or were already overweight; slightly over one half were of normal weight. Initial findings revealed a significant relationship between children's weight category and their reading/language arts, mathematics, and science test scores even after controlling for a proxy of socioeconomic status. When additional cardiovascular risk and fitness measures were included in the model, however, children's BMI status had no association. Instead, a composite fitness index, children's blood pressure, sex, and proxy of socioeconomic status were significantly associated with children's academic test scores. Discussion: This study expanded our understanding of the connection between children's overweight risks and academic performance by examining the impact of other cardiovascular risk factors such as high blood pressure and measures of fitness. These findings support the development and implementation of childhood cardiovascular risk surveillance programs that evaluate not only children's overweight risks but also their fitness, risk for type 2 diabetes, and/or high blood pressure by showing a relationship between some of these risks and children's academic test performance.