Collagen Can Selectively Trigger a Platelet Secretory Phenotype via Glycoprotein VI

Platelets are not only central actors of hemostasis and thrombosis but also of other processes including inflammation, angiogenesis, and tissue regeneration. Accumulating evidence indicates that these “non classical” functions of platelets do not necessarily rely on their well-known ability to form thrombi upon activation. This suggests the existence of non-thrombotic alternative states of platelets activation. We investigated this possibility through dose-response analysis of thrombin- and collagen-induced changes in platelet phenotype, with regards to morphological and functional markers of platelet activation including shape change, aggregation, P-selectin and phosphatidylserine surface expression, integrin activation, and release of soluble factors. We show that collagen at low dose (0.25 µg/mL) selectively triggers a platelet secretory phenotype characterized by the release of dense- and alpha granule-derived soluble factors without causing any of the other major platelet changes that usually accompany thrombus formation. Using a blocking antibody to glycoprotein VI (GPVI), we further show that this response is mediated by GPVI. Taken together, our results show that platelet activation goes beyond the mechanisms leading to platelet aggregation and also includes alternative platelet phenotypes that might contribute to their thrombus-independent functions.     

DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)

Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.     

Attention to elders' voice in non-human primates

The observed respect and attention to elders'' speech in traditional cultures appears to have a ‘universal’ component which questions its possible biological bases. Animals present differential attention to the vocalizations of other individuals according to their characteristics but little is known about the potential propensity to pay more attention to vocalizations of elders. On the basis of several hundreds of vocal exchanges recorded, here we show that aged female Campbell''s monkeys (Cercopithecus campbelli), despite being significantly less ‘loquacious’ than their younger adult counterparts, elicit many more responses when calling. These findings show that attention to elders'' vocal production appears in non-human primates, leading to new lines of questioning on human culture and language evolution.     

Multiple molecular forms of rat superior cervical ganglion acetylcholinesterase: Developmental aspects in primary cell culture and during postnatal maturation in vivo

Four main molecular forms of acetylcholinesterase (AChE) can be solubilized from newborn rat superior cervical ganglia (SCG), homogenized in the presence of a high-ionic-strength, detergent-containing medium. These forms, respectively referred to as 16, 10, 6.5, and 4 S, are characterized by their sedimentation coefficients. Their relative proportions in SCG are notably different in vivo during postnatal maturation, and in culture. The 16-S AChE appears to be mainly neuronal in origin, is maintained in culture independently of original presynaptic in vivo elements, and its cellular pool is not depleted in the presence of tetrodotoxin (TTX).     

Sexing Adult Pale-Winged Starlings Using Morphometric and Discriminant Function Analysis

Accurate sexing of birds is vital for behavioral studies but can be a real problem in the field, especially for monomorphic species. Our goal here was to characterize the morphology of male and female monomorphic pale-winged starlings (Onychognathus nabouroup), a South African sturnid whose plumage is sexually monomorphic. Morphological measurements of genetically sexed animals indicated that males were statistically larger than females for five measurements: Mass, tail length, tarsus length and wing length. By using a Discriminant Function Analysis based on the measurements taken by one ringer, we were able to predict correctly the sex of 81.10% of the birds of data collected in the field and 77.9% of museum skins independently of year of capture and ringer. The model developed here should be useful for further field studies of this species.     

Constitutive autophagy contributes to resistance to TP53-mediated apoptosis in Epstein-Barr virus-positive latency III B-cell lymphoproliferations

The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders and lymphomas. We have previously demonstrated that treating wild-type TP53-expressing B cell lines with the TP53 pathway activator nutlin-3 induced apoptosis in EBV-negative and EBV-positive latency I cells whereas EBV-positive latency III cells remained much more apoptosis-resistant. Here, we report a constitutively high level of autophagy in these resistant cells which express high levels of the proautophagic protein BECN1/Beclin 1 based, at least in part, on the activation of the NFKB signaling pathway by the viral protein LMP1. Following treatment with nutlin-3, several autophagy-stimulating genes were upregulated both in EBV-negative and EBV-positive latency III cells. However the process of autophagy was only triggered in the latter and was associated with an upregulation of SESN1/sestrin 1 and inhibition of MTOR more rapid than in EBV-negative cells. A treatment with chloroquine, an inhibitor of autophagy, potentiated the apoptotic effect of nutlin-3, particularly in those EBV-positive cells which were resistant to apoptosis induced by nutlin-3 alone, thereby showing that autophagy participates in this resistant phenotype. Finally, using immunohistochemical staining, clinical samples from various B cell lymphoproliferations with the EBV-positive latency II or III phenotype were found to harbor a constitutively active autophagy.     

Anaeromyces mucronatus nov. gen., nov. sp. A new strictly anaerobic rumen fungus with polycentric thallus

A new species of strictly anaerobic fungus was isolated from the cow rumen. It is characterized by a polycentric thallus, a polynuclear rhizomycelium, mucronate zoosporangia and uniflagellated zoospores. It is also singular in that the sporocysts do not react to the specific lectins of L-fucose, N-acetyl-D-galactosamine and diacetyl chitobiose. These characteristics justify the creation of a new genus.     

Structural features involved in the mitogenic activity of bordetella pertussis lipopolysaccharides for spleen cells of C3H/HeJ mice

Abstract Spleen cells from the C3H/HeJ mouse strain cannot be stimulated by many smooth-type lipopolysaccharides (LPSs), and by the main biologically-active region (lipid A) of these molecules. The genetic origin of this defect (expression of the mutant allele Lps^d at the chromosome 4 locus) was established over 20 years ago, but its biochemical nature has remained undefined. Several investigators have noted, however, that some particular LPSs can bypass this defect, and stimulate the proliferation of C3H/HeJ B lymphocytes. In this study we compare the mitogenic activities of the LPSs isolated from a wild strain (1414) and from a mutant ‘rough’ strain (A100) of Bordetella pertussis . Both LPS-1414 and LPS-A100 were mitogenic for C3H/HeJ spleen cells, but their lipid A fragments were not. This indicates that a carbohydrate structure proximal to lipid A is involved in the mitogenic activity. However, the isolated polysaccharides were not mitogenic. Four sugars are common to both LPS-1414 and LPS-A100: an heptose, and three sugars bearing free amino groups. After removal of these four sugars from the LPSs by nitrous acid treatment, the recovered lipooligosaccharides were not mitogenic in Lps^d spleen cells. The results suggest that substructures present in lipid A and in this group of four sugars are both required for induction of a mitogenic effect in Lps^d splenocytes, whereas lipid A alone can stimulate Lpsⁿ spleen cells.     

Regulation of the Saccharomyces cerevisiae Srs2 helicase during the mitotic cell cycle, meiosis and after irradiation

The expression of theSRS2 gene, which encodes a DNA helicase involved in DNA repair inSaccharomyces cerevisiae, was studied using anSRS2-lacZ fusion integrated at the chromosomalSRS2 locus. It is shown here that this gene is expressed at a low level and is tightly regulated. It is cell-cycle regulated, with induction probably being coordinated with that of the DNA-synthesis genes, which are transcribed at the G1-S boundary. It is also induced by DNA-damaging agents, but only during the G2 phase of the cell cycle; this distinguishes it from a number of other repair genes, which are inducible throughout the cycle. During meiosis, the expression ofSRS2 rises at a time nearly coincident with commitment to recombination. Sincesrs2 null mutants are radiation sensitive essentially when treated in G1, the mitotic regulation pattern described here leads us to postulate that either secondary regulatory events limit Srs2 activity to G1 cells or Srs2 functions in a repair mechanism associated with replication.