Is the postpharyngeal gland of a solitary digger wasp homologous to ants? Evidence from chemistry and physiology

The postpharyngeal gland (PPG) was thought to be restricted to ants where it serves a crucial function in the generation of the colony odour. Recently, head glands that closely resemble the PPG of ants were discovered in females of a solitary digger wasp, the European beewolf. The function of this gland necessarily differs from ants: beewolf females apply the secretion of their PPG onto the bodies of paralysed honeybees that serve as larval provisions in order to delay fungus growth. Since ants and digger wasps are not closely related, the occurrence of this gland in these two taxa might either be due to convergent evolution or it is a homologous organ inherited from a common ancestor. Here we test the hypothesis that the PPGs of both taxa are homologous by comparing characteristics of chemical composition and physiology of the PPG of beewolves and ants. Based on reported characteristics of the PPG content of ants, we tested three predictions that were all met. First, the PPG of beewolves contained mainly long-chain hydrocarbons and very few compounds with functional groups. Second, the composition of hydrocarbons in the beewolf PPG was similar to that of the hemolymph. Taking the structure of the gland epithelium and the huge requirements of beewolf females for gland secretion into account this result suggests that the content of the PPG is also sequestered from the hemolymph in beewolves. Third, the chemical composition of the PPG and the cuticle was similar in beewolves since cuticular hydrocarbons derive either from the hemolymph or the PPG. Taking the considerable morphological similarities into account, our results support the hypothesis of a homologous origin of the PPG in beewolves and ants

The Chemistry of the Postpharyngeal Gland of Female European Beewolves

Females of the European beewolf, Philanthus triangulum, possess a large glove-shaped gland in the head, the postpharyngeal gland (PPG). They apply the content of the PPG to their prey, paralyzed honeybees, where it delays fungal infestation. Here, we describe the chemical composition of the gland by using combined GC-MS, GC-FTIR, and derivatization. The PPG of beewolves contains mainly long-chain unsaturated hydrocarbons (C23–C33), lower amounts of saturated hydrocarbons (C14–C33), and minor amounts of methyl-branched hydrocarbons (C17–C31). Additionally, the hexane-soluble gland content is comprised of small amounts of an unsaturated C25 alcohol, an unknown sesquiterpene, an octadecenylmethylester, and several long-chain saturated (C25, C27) and unsaturated (C23–C27) ketones, some of which have not yet been reported as natural products. Surprisingly, we found a dimorphism with regard to the major component of the PPG with some females having (Z)-9-pentacosene, whereas others have (Z)-9-heptacosene as their predominant component. The biological relevance of the compounds for the prevention of fungal growth on the prey and the significance of the chemical dimorphism are discussed

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE: To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS: Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS: For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS: Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.status: publishe

Expression of the Lantibiotic Mersacidin in Bacillus amyloliquefaciens FZB42

Lantibiotics are small peptide antibiotics that contain the characteristic thioether amino acids lanthionine and methyllanthionine. As ribosomally synthesized peptides, lantibiotics possess biosynthetic gene clusters which contain the structural gene (lanA) as well as the other genes which are involved in lantibiotic modification (lanM, lanB, lanC, lanP), regulation (lanR, lanK), export (lanT(P)) and immunity (lanEFG). The lantibiotic mersacidin is produced by Bacillus sp. HIL Y-85,54728, which is not naturally competent

IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes

Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response

Molecular mechanisms and cellular functions of cGAS-STING signalling

The cGAS–STING signalling axis, comprising the synthase for the second messenger cyclic GMP–AMP (cGAS) and the cyclic GMP–AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGAS–STING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGAS–STING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-κB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquid–liquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved