Many insect species subsist on decaying and contaminated matter and are thus exposed to large quantities of microorganisms. To control beneficial commensals and combat infectious pathogens, insects must be armed with efficient systems for microbial recognition, signaling pathways, and effector molecules. The molecular mechanisms regulating these host-microbe interactions in insects have been largely clarified in Drosophila melanogaster with its powerful genetic and genomic tools. Here we review recent advances in this field, focusing mainly on the relationships between microbes and epithelial cells in the intestinal tract where the host exposure to the external environment is most frequent.

Summary:Purpose: Despite use of the ketogenic diet (KD) for >75 years its effectiveness or mechanism of action has been examined in few animal studies. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in adult rats.Methods: Rats fully kindled from the amygdala were divided into KD-fed or standard rat diet-fed groups; diet treatment continued for 5 weeks. The KD approximated at 4:l ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was contributed by fat and 8% was contributed by protein. Afterdischarge threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST, SD) were assessed weekly for 5 weeks. During week 3, learning and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test.Results: Rats receiving the KD became ketonemic and had weight gains similar to those of control rats. As compared with rats receiving a standard diet, those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard to ADD or SD at any time during the study, and both groups performed similarly in the water maze and open field test.Conclusions: In the kindling model, the KD afforded transient protection against the focal generation of kindled seizures but not seizure spread. Rats that received the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promising model for study of the anticonvulsant mechanisms of ketosis. Key Words: Ketogenic diet-Kindling-Seizure-Afterdischarge threshold-Water maze.The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has been used for treatment of refi-actory seizures for >75 years (1). Nevertheless, information on the optimal formulation of the diet, the seizure types in which it might be most effective, and the characteristics of patients who might benefit from its use is limited (2,3). Despite extensive clinical use of the KD, surprisingly few investigators have attempted to determine how and even whether the KD works (3,4). Furthermore, although anecdotal reports cite improved cognition and alertness in patients receiving the KD (5,6), this claim has not been evaluated in any well-controlled clinical or experimental studies.The KD was used widely before antiepileptic drugs (AEDs) became available, but since the advent of modern pharmacological therapy, the KD has largely been paring and maintaining a patient on the KD is often a daunting challenge for both family and physician. Recently, however, there has been a resurgence of interest in the KD (2,7), which has given impetus to efforts designed to verify experimentally the effectiveness and optimal indications of this increasingly popular but unconventional therapy.Animal models offer several advantages for investi...

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The long-term consequences of AED treatment during development are related to the drug used. VPA treatment after KA-induced status epilepticus prevents many of the neurologic sequelae typically seen after KA.

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.

Summary:Purpose: While there is increasing evidence that the adverse effects of prolonged seizures are less pronounced in the immature than in the mature brain, there have been few investigations of the long-term effects of recurrent seizures during development. This study examined the effects of multiple administrations of the convulsant kainic acid (KA) on seizure characteristics and spatial learning as a function of brain development.Metho& To determine the long-term effects of serial KA seizures during ontogeny, saline or convulsant doses of KA were given intraperitoneally 4 times, at 2-day intervals. Immature rats were given KA on P20, P22, P24 and P26; adult rats got KA on P60, P62, P64 and P66. Ictal characteristics and EEGs were recorded. To examine the effects of multiple KA seizures on the retention of spatial learning, water maze testing was performed before (immature group: from P16-19, adult group: from P56-P59) and after (immature: from P60-P63, adult: from PIOO-Pl03) KA injections. Finally, histology was performed to compare KA-induced damage at each age.Results: In immature animals, serial KA administration resulted in seizures with a progressively longer onset latency and decreased severity. In contrast, KA serially administered to adult rats caused severe seizures after each of the 4 injections.In immature rats, epileptiform EEG changes were most prominent after the first KA injection, whereas in adults, prolonged paroxysmal EEG patterns were seen after all 4 KA injections. Before KA, both rat pups and adults acquired place learning in the water maze. One month after the final KA injection, there was no deficit in spatial learning retention in the immature group, whereas the adult group had profound impairment compared to age-matched, saline-injected controls. Histology revealed no lesions in immature rats treated multiple times with KA but profound cell loss in hippocampal fields CA4, CA3 and CAI in rats treated serially with KA as adults.Conclusions: Previous studies have shown that a single KA injection causes prolonged status epilepticus (which persists for several hours), leading to severe histologic and behavioral sequelae in adult rats but not in pups. Our study extends those findings, demonstrating that immature rats are spared the cognitive and pathological sequelae of multiple injections of convulsant doses of KA as well.

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Drosophila adults have been utilized as a genetically tractable model organism to decipher the molecular mechanisms of humoral innate immune responses. In an effort to promote the utility of Drosophila larvae as an additional model system, in this study, we describe a novel aspect of an induction mechanism for innate immunity in these larvae. By using a fine tungsten needle created for manipulating semi-conductor devices, larvae were subjected to septic injury. However, although Toll pathway mutants were susceptible to infection with Gram-positive bacteria as had been shown for Drosophila adults, microbe clearance was not affected in the mutants. In addition, Drosophila larvae were found to be sensitive to mechanical stimuli with respect to the activation of a sterile humoral response. In particular, pinching with forceps to a degree that might cause minor damage to larval tissues could induce the expression of the antifungal peptide gene Drosomycin; notably, this induction was partially independent of the Toll and immune deficiency pathways. We therefore propose that Drosophila larvae might serve as a useful model to analyze the infectious and non-infectious inflammation that underlies various inflammatory diseases such as ischemia, atherosclerosis and cancer.