In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p\u27-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p\u27-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p\u27-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p\u27-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p\u27-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p\u27-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p\u27-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p\u27-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p\u27-DDT was dependent on the FSHR. In addition, p,p\u27-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p\u27-DDT and potentiation of the FSHR response to FSH by p,p\u27-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p\u27-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p\u27-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION:p,p\u27-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptor

Reciprocal genomic evolution in the ant-fungus agricultural symbiosis

The attine ant–fungus agricultural symbiosis evolved over tens of millions of years, producing complex societies with industrial-scale farming analogous to that of humans. Here we document reciprocal shifts in the genomes and transcriptomes of seven fungus-farming ant species and their fungal cultivars. We show that ant subsistence farming probably originated in the early Tertiary (55–60 MYA), followed by further transitions to the farming of fully domesticated cultivars and leaf-cutting, both arising earlier than previously estimated. Evolutionary modifications in the ants include unprecedented rates of genome-wide structural rearrangement, early loss of arginine biosynthesis and positive selection on chitinase pathways. Modifications of fungal cultivars include loss of a key ligninase domain, changes in chitin synthesis and a reduction in carbohydrate-degrading enzymes as the ants gradually transitioned to functional herbivory. In contrast to human farming, increasing dependence on a single cultivar lineage appears to have been essential to the origin of industrial-scale ant agriculture

Wolbachia in the flesh: symbiont intensities in germ-line and somatic tissues challenge the conventional view of Wolbachia transmission routes

Symbionts can substantially affect the evolution and ecology of their hosts. The investigation of the tissue-specific distribution of symbionts (tissue tropism) can provide important insight into host-symbiont interactions. Among other things, it can help to discern the importance of specific transmission routes and potential phenotypic effects. The intracellular bacterial symbiont Wolbachia has been described as the greatest ever panzootic, due to the wide array of arthropods that it infects. Being primarily vertically transmitted, it is expected that the transmission of Wolbachia would be enhanced by focusing infection in the reproductive tissues. In social insect hosts, this tropism would logically extend to reproductive rather than sterile castes, since the latter constitute a dead-end for vertically transmission. Here, we show that Wolbachia are not focused on reproductive tissues of eusocial insects, and that non-reproductive tissues of queens and workers of the ant Acromyrmex echinatior, harbour substantial infections. In particular, the comparatively high intensities of Wolbachia in the haemolymph, fat body, and faeces, suggest potential for horizontal transmission via parasitoids and the faecal-oral route, or a role for Wolbachia modulating the immune response of this host. It may be that somatic tissues and castes are not the evolutionary dead-end for Wolbachia that is commonly thought

The Dynamics of Plant Cell-Wall Polysaccharide Decomposition in Leaf-Cutting Ant Fungus Gardens

The degradation of live plant biomass in fungus gardens of leaf-cutting ants is poorly characterised but fundamental for understanding the mutual advantages and efficiency of this obligate nutritional symbiosis. Controversies about the extent to which the garden-symbiont Leucocoprinus gongylophorus degrades cellulose have hampered our understanding of the selection forces that induced large scale herbivory and of the ensuing ecological footprint of these ants. Here we use a recently established technique, based on polysaccharide microarrays probed with antibodies and carbohydrate binding modules, to map the occurrence of cell wall polymers in consecutive sections of the fungus garden of the leaf-cutting ant Acromyrmex echinatior. We show that pectin, xyloglucan and some xylan epitopes are degraded, whereas more highly substituted xylan and cellulose epitopes remain as residuals in the waste material that the ants remove from their fungus garden. These results demonstrate that biomass entering leaf-cutting ant fungus gardens is only partially utilized and explain why disproportionally large amounts of plant material are needed to sustain colony growth. They also explain why substantial communities of microbial and invertebrate symbionts have evolved associations with the dump material from leaf-cutting ant nests, to exploit decomposition niches that the ant garden-fungus does not utilize. Our approach thus provides detailed insight into the nutritional benefits and shortcomings associated with fungus-farming in ants

Sex Determination in Honeybees: Two Separate Mechanisms Induce and Maintain the Female Pathway

Sex determination in honeybees is realized by the csd and the fem gene that establish and maintain, throughout development, sexual fates via the control of alternative splicing

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Initial stage of cheese production: a molecular modeling study of bovine and camel chymosin complexed with peptides from the chymosin-sensitive region of kappa-casein

Bovine chymosin has long been the preferred enzyme used to coagulate cow's milk, in the initial stage of cheese production, during which it cleaves a specific bond in the milk protein kappa-casein. Recently, camel chymosin has been shown to have a 70% higher clotting activity toward cow's milk and, moreover, to cleave kappa-casein more selectively. Bovine chymosin, on the other hand, is a poor clotting agent toward camel's milk. This paper reports a molecular modeling study aimed at understanding this disparity, based on homology modeling and molecular dynamics simulations using peptide fragments of kappa-casein from cow and camel in both bovine and camel chymosin. The results show that the complex between bovine chymosin and the fragment of camel kappa-casein is indeed less stable in the binding pocket. The results also indicate that this in part may be due to charge repulsion between a lysine residue in bovine chymosin and an arginine residue in the P4 position of camel kappa-casein