Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia

Globozoospermia is a rare (incidence <0.1% in male infertile patients) form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. It originates from a disturbed spermiogenesis, which is expected to be induced by a genetic factor. Several family cases and recessive mouse models with the same phenotype support this expectation. In this study, we present a consanguineous family with three affected brothers, in whom we have identified a homozygous mutation in the spermatogenesis-specific gene SPATA16. This is the first example of a nonsyndromic male infertility condition in humans caused by an autosomal gene defect, and it could also mean that the identification of other partners like SPATA16 could elucidate acrosome formation.     

Calcite and aragonite distributions in the skeletons of bimineralic bryozoans as revealed by Raman spectroscopy

Abstract. Bryozoans are among a diverse range of invertebrates capable of secreting calcium carbonate skeletons. Relatively little is known about biomineralization in bryozoans, despite the importance of understanding biomineralization processes for nanotechnology and the threats imposed by ocean acidification on organisms having calcareous skeletons. Ten species of cheilostome bryozoans that are reported to have bimineralic skeletons of calcite and aragonite are studied here using Raman spectroscopy. This technique allowed identification of the two mineral phases at submicron spatial resolution, allowing the distributions of calcite and aragonite within bryozoan skeletons to be determined with unprecedented precision. Confirming previous findings based on the use of chemical stains, most of the bimineralic species analyzed exhibited a calcitic skeletal framework, composed of basal, vertical, and inner frontal walls, having aragonite deposited subsequently onto the outer surfaces of the frontal walls. In one species ( Odontionella cyclops ), aragonite formed the superstructure above the autozooids, and in two others, traces of aragonite were detected on the undersides of the frontal shields. Using Raman spectroscopy, it was possible for the first time to determine the mineralogy of small-scale structures, including orificial rims, condyles and hinge teeth, avicularian pivotal bars and rostra, and ascopore rims and sieve plates. Even when surrounded by aragonitic frontal shields, these structures were found typically to be calcitic, the two exceptions being the aragonitic avicularia of Stylopoma inchoans and O. cyclops . Unexpectedly, the first-formed part of the basal wall at the distalmost growing edge of Pentapora foliacea was found to consist mainly of aragonite. This may point to a precursory phase of biomineralization comparable with the unusual mineralogies identified previously in the earliest-formed skeletons of members of some other invertebrate phyla.     

Reversing systemic inflammatory response syndrome with chemokine receptor pepducins

We describe a new therapeutic approach for the treatment of lethal sepsis using cell-penetrating lipopeptides-termed pepducins-that target either individual or multiple chemokine receptors. Interleukin-8 (IL-8), a ligand for the CXCR1 and CXCR2 receptors, is the most potent endogenous proinflammatory chemokine in sepsis. IL-8 levels rise in blood and lung fluids to activate neutrophils and other cells, and correlate with shock, lung injury and high mortality. We show that pepducins derived from either the i1 or i3 intracellular loops of CXCR1 and CXCR2 prevent the IL-8 response of both receptors and reverse the lethal sequelae of sepsis, including disseminated intravascular coagulation and multi-organ failure in mice. Conversely, pepducins selective for CXCR4 cause a massive leukocytosis that does not affect survival. CXCR1 and CXCR2 pepducins conferred nearly 100% survival even when treatment was postponed, suggesting that our approach might be beneficial in the setting of advanced disease.     

IL-10 is critical for host resistance and survival during gastrointestinal helminth infection

Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections. The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated. In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity. Interestingly, T. muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality. In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12. Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals. The mortality observed in T. muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum. Interestingly, survival was enhanced in T. muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality. Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T. muris infection, and maintenance of barrier function in the colon.     

Stress resistance and longevity are not directly linked to levels of enzymatic antioxidants in the ponerine ant Harpegnathos saltator

Background

The molecular mechanisms of variations in individual longevity are not well understood, even though longevity can be increased substantially by means of diverse experimental manipulations. One of the factors supposed to be involved in the increase of longevity is a higher stress resistance. To test this hypothesis in a natural system, eusocial insects such as bees or ants are ideally suited. In contrast to most other eusocial insects, ponerine ants show a peculiar life history that comprises the possibility to switch during adult life from a normal worker to a reproductive gamergate, therewith increasing their life expectancy significantly.

Results

We show that increased resistance against major stressors, such as reactive oxygen species and infection accompanies the switch from a life-history trait with normal lifespan to one with a longer life expectancy. A short period of social isolation was sufficient to enhance stress resistance of workers from the ponerine ant species Harpegnathos saltator significantly. All ant groups with increased stress resistances (reproducing gamergates and socially isolated workers) have lower catalase activities and glutathione levels than normal workers. Therewith, these ants resemble the characteristics of the youngest ants in the colony.

Conclusions

Social insects with their specific life history including a switch from normal workers to reproducing gamergates during adult life are well suited for ageing research. The regulation of stress resistance in gamergates seemed to be modified compared to foraging workers in an economic way. Interestingly, a switch towards more stress resistant animals can also be induced by a brief period of social isolation, which may already be associated with a shift to a reproductive trajectory. In Harpegnathos saltator, stress resistances are differently and potentially more economically regulated in reproductive individuals, highlighting the significance of reproduction for an increase in longevity in social insects. As already shown for other organisms with a long lifespan, this trait is not directly coupled to higher levels of enzymatic and non-enzymatic antioxidants.     

Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception

The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects’ genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus for sensitivity to amarogentin, one of the most bitter natural compounds known, and two loci for sensitivity to grosheimin, one of the bitter compounds of artichoke. Our analyses revealed also, besides simple associations, complex associations of bitterness sensitivity across TAS2R loci. Indeed, even if several putative loci harbored both high- and low-sensitivity alleles, phenotypic variation depended on linkage between these alleles. When sensitive alleles for bitter compounds were maintained in the same linkage phase, genetically driven perceptual differences were obvious, e.g. for grosheimin. On the contrary, when sensitive alleles were in opposite phase, only weak genotype-phenotype associations were seen, e.g. for absinthin, the bitter principle of the beverage absinth. These findings illustrate the extent to which genetic influences on taste are complex, yet arise from both receptor activation patterns and linkage structure among receptor genes.     

Interspecific competition between the braconid endoparasitoids Glyptapanteles porthetriae and Glyptapanteles liparidis in Lymantria dispar larvae

The effect of interspecific competition between the solitary endoparasitoid Glyptapanteles porthetriae Muesebeck (Hymenoptera: Braconidae) and the gregarious Glyptapanteles liparidis Bouché (Hymenoptera: Braconidae), was investigated in larvae of Lymantria dispar L. (Lepidoptera: Lymantriidae). Host larvae were parasitized by both wasp species simultaneously in premolt to the 2^nd or the 3^rd host instar or in an additional approach with a 4‐day delay in parasitization by the second wasp species. Host acceptance experiments revealed that both wasp species do not discriminate between unparasitized host larvae and larvae parasitized previously by the same or the other species. In more than 90% female wasps parasitized the larva they encountered first. During the period of endoparasitic development, larvae of the competing parasitoid species never attacked the egg stage of the other species. When host larvae were parasitized simultaneously by both wasp species, the rate of successful development of both species depended on the age of the host larva at the time of its parasitization; G. liparidis emerged successfully from 44% of host larvae parasitized during the premolt to 2^nd instar, G. porthetriae from 28%, and in 20% of the hosts both parasitoid species were able to develop in one gypsy moth larva. However, when host larvae were parasitized simultaneously during premolt to the 3^rd instar, G. liparidis was successful in 90% of the hosts, compared to 8% from which only G. porthetriae emerged. In the experiments with delayed oviposition, generally the species that oviposited first succeeded in completing its larval development. Larvae of the species ovipositing with four days delay were frequently attacked and killed by larvae of the first parasitizing species or suffered reduced growth. As the secondary parasitoid species, G. porthetriae‐larvae were never able to complete their development, whereas G. liparidis developed successfully in at least 12,5% of the multiparasitized host larvae. Thus, multiparasitism of gypsy moth larvae by both Glyptapanteles species corresponds to the contest type; however, G. porthetriae is only able to develop successfully as the primary parasitoid of young host larvae.     

Quantitative analysis of micro-CT imaging and histopathological signatures of experimental arthritis in rats

Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10) stored in formalin consisted of approximately 600 30-mum slices acquired on a 512 x 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.