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

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

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

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

Symbiotic bacteria protect wasp larvae from fungal infestation

AbstractSymbiotic associations between different organisms are of great importance for evolutionary and ecological processes [1–4]. Bacteria are particularly valuable symbiotic partners owing to their huge diversity of biochemical pathways that may open entirely new ecological niches for higher organisms [1–3]. Here, we report on a unique association between a new Streptomyces species and a solitary hunting wasp, the European beewolf (Philanthus triangulum, Hymenoptera, Crabronidae). Beewolf females cultivate the Streptomyces bacteria in specialized antennal glands and apply them to the brood cell prior to oviposition. The bacteria are taken up by the larva and occur on the walls of the cocoon. Bioassays indicate that the streptomycetes protect the cocoon from fungal infestation and significantly enhance the survival probability of the larva, possibly by producing antibiotics. Behavioral observations strongly suggest a vertical transmission of the bacteria. Two congeneric beewolf species harbor closely related streptomycetes in their antennae, indicating that the association with protective bacteria is widespread among philanthine wasps and might play an important role in other insects as well. This is the first report on the cultivation of bacteria in insect antennae and the first case of a symbiosis involving bacteria of the important antibiotic-producing genus Streptomyces