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To help address the underrepresentation of arthropods and Asian biodiversity from climate-change assessments, we carried out year-long, weekly sampling campaigns with Malaise traps at different elevations and latitudes in Gaoligongshan National Park in southwestern China. From these 623 samples, we barcoded 10,524 beetles and compared scenarios of climate-change-induced biodiversity loss, by designating seasonal, elevational, and latitudinal subsets of beetles as communities that plausibly could go extinct as a group, which we call "loss sets". The availability of a published mitochondrial-genome-based phylogeny of the Coleoptera allowed us to compare the loss of species diversity with and without accounting for phylogenetic relatedness. We hypothesised that phylogenetic relatedness would mitigate extinction, since the extinction of any loss set would result in the disappearance of all its species but only part of its evolutionary history, which is still extant in the remaining loss sets. We found different patterns of community clustering by season and latitude, depending on whether phylogenetic information was incorporated. However, accounting for phylogeny only slightly mitigated the amount of biodiversity loss under climate change scenarios, against our expectations: there is no phylogenetic "escape clause" for biodiversity conservation. We achieve the same results whether phylogenetic information was derived from the mitogenome phylogeny or from a de novo barcode-gene tree. We encourage interested researchers to use this data set to study lineage-specific community assembly patterns in conjunction with life-history traits and environmental covariates.

MotivationNovel recombinant viruses may have important medical and evolutionary significance, as they sometimes display new traits not present in the parental strains. This is particularly concerning when the new viruses combine fragments coming from phylogenetically-distinct viral types. Here, we consider the task of screening large collections of sequences for such novel recombinants. A number of methods already exist for this task. However, these methods rely on complex models and heavy computations that are not always practical for a quick scan of a large number of sequences.ResultsWe have developed SHERPAS, a new program to detect novel recombinants and provide a first estimate of their parental composition. Our approach is based on the precomputation of a large database of “phylogenetically-informed k-mers”, an idea recently introduced in the context of phylogenetic placement in metagenomics. Our experiments show that SHERPAS is hundreds to thousands of times faster than existing software, and enables the analysis of thousands of whole genomes, or long sequencing reads, within minutes or seconds, and with limited loss of accuracy.Availability and ImplementationThe source code is freely available for download at https://github.com/phylo42/sherpasContactpardi@lirmm.fr, gllm.scholz@gmail.comSupplementary informationSupplementary Materials are available online.

Motivation Phylogenetic placement (PP) is a process of taxonomic identification for which several tools are now available. However, it remains difficult to assess which tool is more adapted to particular genomic data or a particular reference taxonomy. We developed Placement Evaluation WOrkflows (PEWO), the first benchmarking tool dedicated to PP assessment. Its automated workflows can evaluate PP at many levels, from parameter optimization for a particular tool, to the selection of the most appropriate genetic marker when PP-based species identifications are targeted. Our goal is that PEWO will become a community effort and a standard support for future developments and applications of PP. Availability and implementation https://github.com/phylo42/PEWO. Supplementary information Supplementary data are available at Bioinformatics online.

High-throughput DNA methods hold great promise for phylogenetic analysis of lineages that are difficult to study with conventional molecular and morphological approaches. The mites (Acari), and in particular the highly diverse soil-dwelling lineages, are among the least known branches of the metazoan Tree-of-Life. We extracted numerous minute mites from soils in an area of mixed forest and grassland in southern Iberia. Selected specimens representing the full morphological diversity were shotgun sequenced in bulk, followed by genome assembly of short reads from the mixture, which produced >100 mitochondrial genomes representing diverse acarine lineages. Phylogenetic analyses in combination with taxonomically limited mitogenomes available publicly resulted in plausible trees defining basal relationships of the Acari. Several critical nodes were supported by ancestral-state reconstructions of mitochondrial gene rearrangements. Molecular calibration placed the minimum age for the common ancestor of the superorder Acariformes, which includes most soil-dwelling mites, to the Cambrian–Ordovician (likely within 455–552 Ma), whereas the origin of the superorder Parasitiformes was placed later in the Carboniferous-Permian. Most family-level taxa within the Acariformes were dated to the Jurassic and Triassic. The ancient origin of Acariformes and the early diversification of major extant lineages linked to the soil are consistent with a pioneering role for mites in building the earliest terrestrial ecosystems., This research was funded by the NHM Biodiversity Initiative and the CGL2015-66192-R and CGL2015-74178-JIN projects. PA was supported by the Royal Society UK (Newton International Program) and the Spanish Ministry of Economy and Competitiveness (Juan de la Cierva Formación); BL by the NHM Biodiversity Initiative and French Labex Agro-CeMEB-NUMEV

A phylogenetic tree at the species level is still far off for highly diverse insect orders, including the Coleoptera, but the taxonomic breadth of public sequence databases is growing. In addition, new types of data may contribute to increasing taxon coverage, such as metagenomic shotgun sequencing for assembly of mitogenomes from bulk specimen samples. The current study explores the application of these techniques for large-scale efforts to build the tree of Coleoptera. We used shotgun data from 17 different ecological and taxonomic datasets (5 unpublished) to assemble a total of 1942 mitogenome contigs of >3000 bp. These sequences were combined into a single dataset together with all mitochondrial data available at GenBank, in addition to nuclear markers widely used in molecular phylogenetics. The resulting matrix of nearly 16,000 species with two or more loci produced trees (RAxML) showing overall congruence with the Linnaean taxonomy at hierarchical levels from suborders to genera. We tested the role of full-length mitogenomes in stabilizing the tree from GenBank data, as mitogenomes might link terminals with non-overlapping gene representation. However, the mitogenome data were only partly useful in this respect, presumably because of the purely automated approach to assembly and gene delimitation, but improvements in future may be possible by using multiple assemblers and manual curation. In conclusion, the combination of data mining and metagenomic sequencing of bulk samples provided the largest phylogenetic tree of Coleoptera to date, which represents a summary of existing phylogenetic knowledge and a defensible tree of great utility, in particular for studies at the intra-familial level, despite some shortcomings for resolving basal nodes., This work was funded by the Biodiversity Initiative of the NHM and NERC grant NE/M021955. PA received funding through a Newton Fellowship of the Royal Society.

High-throughput DNA methods hold great promise for the study of the hyperdiverse arthropod fauna of the soil. We used the mitochondrial metagenomic approach to generate 39 mitochondrial genomes from adult and larval specimens of Coleoptera collected from soil samples. The mitogenomes correspond to species from the families Carabidae (6), Chrysomelidae (1), Curculionidae (9), Dermestidae (1), Elateridae (1), Latridiidae (1), Scarabaeidae (3), Silvanidae (1), Staphylinidae (12), and Tenebrionidae (4). All the mitogenomes followed the putative ancestral gene order for Coleoptera. We provide the first available mitogenome for 30 genera of Coleoptera, including endogean representatives of the genera Torneuma, Coiffaitiella, Otiorhynchus, Oligotyphlopsis, and Typhlocharis., The study was funded by the NHM Biodiversity Initiative (UK) and the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía y Competitividad) under a project with the number CGL2015-74178-JIN.

Motivation Taxonomic classification is at the core of environmental DNA analysis. When a phylogenetic tree can be built as a prior hypothesis to such classification, phylogenetic placement (PP) provides the most informative type of classification because each query sequence is assigned to its putative origin in the tree. This is useful whenever precision is sought (e.g. in diagnostics). However, likelihood-based PP algorithms struggle to scale with the ever-increasing throughput of DNA sequencing. Results We have developed RAPPAS (Rapid Alignment-free Phylogenetic Placement via Ancestral Sequences) which uses an alignment-free approach, removing the hurdle of query sequence alignment as a preliminary step to PP. Our approach relies on the precomputation of a database of k-mers that may be present with non-negligible probability in relatives of the reference sequences. The placement is performed by inspecting the stored phylogenetic origins of the k-mers in the query, and their probabilities. The database can be reused for the analysis of several different metagenomes. Experiments show that the first implementation of RAPPAS is already faster than competing likelihood-based PP algorithms, while keeping similar accuracy for short reads. RAPPAS scales PP for the era of routine metagenomic diagnostics. Availability and implementation Program and sources freely available for download at https://github.com/blinard-BIOINFO/RAPPAS. Supplementary information Supplementary data are available at Bioinformatics online.

International audience; DNA methods are useful to identify ingested prey items from the gut of predators, but reliable detection is hampered by low amounts of degraded DNA. PCR-based methods can retrieve minute amounts of starting material but suffer from amplification biases and cross-reactions with the predator and related species genomes. Here, we use PCR-free direct shotgun sequencing of total DNA isolated from the gut of the harlequin ladybird Harmonia axyridis at five time points after feeding on a single pea aphid Acyrthosiphon pisum. Sequence reads were matched to three reference databases: Insecta mitogenomes of 587 species, including H. axyridis sequenced here; A. pisum nuclear genome scaffolds; and scaffolds and complete genomes of 13 potential bacterial symbionts. Immediately after feeding , multicopy mtDNA of A. pisum was detected in tens of reads, while hundreds of matches to nuclear scaffolds were detected. Aphid nuclear DNA and mtDNA decayed at similar rates (0.281 and 0.11 h À1 respectively), and the detectability periods were 32.7 and 23.1 h. Metagenomic sequencing also revealed thousands of reads of the obligate Buchnera aphidicola and facultative Regiella insecticola aphid symbionts, which showed exponential decay rates significantly faster than aphid DNA (0.694 and 0.80 h À1 , respectively). However, the facultative aphid symbionts Hamil-tonella defensa, Arsenophonus spp. and Serratia symbiotica showed an unexpected temporary increase in population size by 1–2 orders of magnitude in the predator guts before declining. Metagenomics is a powerful tool that can reveal complex relationships and the dynamics of interactions among predators, prey and their symbionts.

We introduce a multi-factorial, multi-level approach to build and explore evolutionary scenarios of complex protein networks. EvoKEN combines a unique formalism for integrating multiple types of data associated with network molecular components and knowledge extraction techniques for detecting cohesive/anomalous evolutionary processes. We analyzed known human pathway maps and identified perturbations or specializations at the local topology level that reveal important evolutionary and functional aspects of these cellular systems.

International audience; The complete mitochondrial genome of the recently discovered beetle family Iberobaeniidae is described and compared with known coleopteran mitogenomes. The mitochondrial sequence was obtained by shotgun metagenomic sequencing using the Illumina Miseq technology and resulted in an average coverage of 130 × and a minimum coverage of 35×. The mitochondrial genome of Iberobaeniidae includes 13 protein-coding genes, 2 rRNAs, 22 tRNAs genes, and 1 putative control region, and showed a unique rearrangement of protein-coding genes. This is the first rearrangement affecting the relative position of protein-coding and ribosomal genes reported for the order Coleoptera.

International audience; TFIIH is a eukaryotic complex composed of two subcomplexes, the CAK (Cdk activating kinase) and the core-TFIIH. The core-TFIIH, composed of seven subunits (XPB, XPD, P62, P52, P44, P34, and P8), plays a crucial role in transcription and repair. Here, we performed an extended sequence analysis to establish the accurate phy-logenetic distribution of the core-TFIIH in 63 eukaryotic organisms. In spite of the high conservation of the seven subunits at the sequence and genomic levels, the non-enzymatic P8, P34, P52 and P62 are absent from one or a few unicellular species. To gain insight into their respective roles, we undertook a comparative genomic analysis of the whole proteome to identify the gene sets sharing similar presence/absence patterns. While little information was inferred for P8 and P62, our studies confirm the known role of P52 in repair and suggest for the first time the implication of the core TFIIH in mRNA splicing via P34.

International audience; Characterizing trophic networks is fundamental to many questions in ecology, but this typically requires painstaking efforts, especially to identify the diet of small generalist predators. Several attempts have been devoted to develop suitable molecular tools to determine predatory trophic interactions through gut content analysis, and the challenge has been to achieve simultaneously high taxonomic breadth and resolution. General and practical methods are still needed, preferably independent of PCR amplification of barcodes, to recover a broader range of interactions. Here we applied shotgun-sequencing of the DNA from arthro-pod predator gut contents, extracted from four common coccinellid and dermapteran predators co-occurring in an agroecosystem in Brazil. By matching unassembled reads against six DNA reference databases obtained from public databases and newly assembled mito-genomes, and filtering for high overlap length and identity, we identified prey and other foreign DNA in the predator guts. Good taxonomic breadth and resolution was achieved (93% of prey identified to species or genus), but with low recovery of matching reads. Two to nine trophic interactions were found for these predators, some of which were only inferred by the presence of parasitoids and components of the microbiome known to be associated with aphid prey. Intraguild predation was also found, including among closely related ladybird species. Uncertainty arises from the lack of comprehensive reference databases and reliance on low numbers of matching reads accentuating the risk of false positives. We discuss caveats and some future prospects that could improve the use of direct DNA shotgun-sequencing to characterize arthropod trophic networks.

Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision–recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods., Nature Methods, 13 (5), ISSN:1548-7105, ISSN:1548-7091

Field‐collected specimens of invertebrates are regularly killed and preserved in ethanol, prior to DNA extraction from the specimens, while the ethanol fraction is usually discarded. However, DNA may be released from the specimens into the ethanol, which can potentially be exploited to study species diversity in the sample without the need for DNA extraction from tissue. We used shallow shotgun sequencing of the total DNA to characterize the preservative ethanol from two pools of insects (from a freshwater habitat and terrestrial habitat) to evaluate the efficiency of DNA transfer from the specimens to the ethanol. In parallel, the specimens themselves were subjected to bulk DNA extraction and shotgun sequencing, followed by assembly of mitochondrial genomes for 39 of 40 species in the two pools. Shotgun sequencing from the ethanol fraction and read‐matching to the mitogenomes detected ~40% of the arthropod species in the ethanol, confirming the transfer of DNA whose quantity was correlated to the biomass of specimens. The comparison of diversity profiles of microbiota in specimen and ethanol samples showed that ‘closed association’ (internal tissue) bacterial species tend to be more abundant in DNA extracted from the specimens, while ‘open association’ symbionts were enriched in the preservative fluid. The vomiting reflex of many insects also ensures that gut content is released into the ethanol, which provides easy access to DNA from prey items. Shotgun sequencing of DNA from preservative ethanol provides novel opportunities for characterizing the functional or ecological components of an ecosystem and their trophic interactions., This research was funded by the Leverhulme Trust (grant F/00696/P to APV) and the NHM Biodiversity Initiative. PA was supported by two postdoctoral grants from the Royal Society (Newton International Program, UK) and the Spanish Ministry of Economy and Competitiveness (Juan de la Cierva Formación Program, Spain). ACP was funded by a NHM/UCL joint PhD studentship. CA received additional support of a Synthesys grant (GB‐TAF‐2966) and a postdoctoral NERC grant (NE/L013134/1).

International audience; We describe the mitochondrial genome of Hydropsyche pellucidula Curtis 1834, which is first described for the suborder Annulipalpia and the first in the order Trichoptera to show a non-canonical gene order. The mitogenome was obtained by de novo assembly of shotgun sequenced total genomic DNA using Illumina Miseq technology, which produced an average coverage of 115× and a minimum coverage of 48×. The mitochondrial genome includes 13 protein-coding genes, 2 rRNAs and 22 tRNAs. The genome is characterized by a rearrangement in the relative position of protein-coding and ribosomal genes. This mitogenome sequence will be useful for studying the family Hydropsychidae, which is commonly used for freshwater pollution biomonitoring.

Summary Purpose: Although the number of antiepileptic drugs (AEDs) is increasing, none displays neuroprotective or antiepileptogenic properties that could prevent status epilepticus (SE)–induced drug-resistant epilepsy. Ketogenic diet (KD) and calorie restriction (CR) are proposed as alternative treatments in epilepsy. Our goal was to assess the neuroprotective or antiepileptogenic effect of these diets in a well-characterized model of mesial temporal lobe epilepsy following initial SE induced by lithium-pilocarpine in adult rats. Methods: Seventy-five P50 male Wistar rats were fed a specific diet: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), or hypocalorie ketogenic (HK). Rats were subjected to lithium-pilocarpine SE, except six NC to constitute a control group for histology (C). Four rats per group were implanted with epidural electrodes to record electroencephalography (EEG) during SE and the next six following days. From the seventh day, the animals were video-recorded 10 h daily to determine latency to epilepsy onset. Neuronal loss in hippocampus and parahippocampal cortices was analyzed 1 month after the first spontaneous seizure. Results: After lithium-pilocarpine injection, neither KD nor CR modified SE features or latency to epilepsy. In hippocampal layers, KD or CR exhibited a neuroprotective potential without cooperative effect. Parahippocampal cortices were not protected by the diets. Conclusion: The antiepileptic effect of KD and/or CR is overwhelmed by lithium-pilocarpine injection. The isolated protection of hippocampal layers induced by KD or CR or their association failed to modify the course of epileptogenesis.

Metagenomic analyses are challenging in metazoans, but high-copy number and repeat regions can be assembled from low-coverage sequencing by " genome skimming, " which is applied here as a new way of characterizing metagenomes obtained in an ecological or taxonomic context. Illumina shotgun sequencing on two pools of Coleoptera (beetles) of approximately 200 species each were assembled into tens of thousands of scaffolds. Repeated low-coverage sequencing recovered similar scaffold sets consistently, although approximately 70% of scaffolds could not be identified against existing genome databases. Identifiable scaffolds included mitochondrial DNA, conserved sequences with hits to expressed sequence tag and protein databases, and known repeat elements of high and low complexity, including numerous copies of rRNA and histone genes. Assemblies of histones captured a diversity of gene order and primary sequence in Coleoptera. Scaffolds with similarity to multiple sites in available coleopteran genome sequences for Dendroctonus and Tribolium revealed high specificity of scaffolds to either of these genomes, in particular for high-copy number repeats. Numerous " clusters " of scaffolds mapped to the same genomic site revealed intra-and/or intergenomic variation within a metagenome pool. In addition to effect of taxonomic composition of the metagenomes, the number of mapped scaffolds also revealed structural differences between the two reference genomes, although the significance of this striking finding remains unclear. Finally, apparently exogenous sequences were recovered, including potential food plants, fungal pathogens, and bacterial symbionts. The " metagenome skimming " approach is useful for capturing the genomic diversity of poorly studied, species-rich lineages and opens new prospects in environmental genomics.

International audience; A major challenge in the post-genomic era is a better understanding of how human genetic alterations involved in disease affect the gene products. The KD4v (Comprehensible Knowledge Discovery System for Missense Variant) server allows to characterize and predict the phenotypic effects (deleteri-ous/neutral) of missense variants. The server provides a set of rules learned by Induction Logic Programming (ILP) on a set of missense variants described by conservation, physico-chemical, functional and 3D structure predicates. These rules are interpretable by non-expert humans and are used to accurately predict the deleterious/neutral status of an unknown mutation. The web server is available at http://decrypthon.igbmc.fr/kd4v.

Background The data from high throughput genomics technologies provide unique opportunities for studies of complex biological systems, but also pose many new challenges. The shift to the genome scale in evolutionary biology, for example, has led to many interesting, but often controversial studies. It has been suggested that part of the conflict may be due to errors in the initial sequences. Most gene sequences are predicted by bioinformatics programs and a number of quality issues have been raised, concerning DNA sequencing errors or badly predicted coding regions, particularly in eukaryotes. Results We investigated the impact of these errors on evolutionary studies and specifically on the identification of important genetic events. We focused on the detection of asymmetric evolution after duplication, which has been the subject of controversy recently. Using the human genome as a reference, we established a reliable set of 688 duplicated genes in 13 complete vertebrate genomes, where significantly different evolutionary rates are observed. We estimated the rates at which protein sequence errors occur and are accumulated in the higher-level analyses. We showed that the majority of the detected events (57%) are in fact artifacts due to the putative erroneous sequences and that these artifacts are sufficient to mask the true functional significance of the events. Conclusions Initial errors are accumulated throughout the evolutionary analysis, generating artificially high rates of event predictions and leading to substantial uncertainty in the conclusions. This study emphasizes the urgent need for error detection and quality control strategies in order to efficiently extract knowledge from the new genome data.

International audience; Evolutionary systems biology aims to uncover the general trends and principles governing the evolution of biological networks. An essential part of this process is the reconstruction and analysis of the evolutionary histories of these complex, dynamic networks. Unfortunately, the methodologies for representing and exploiting such complex evolutionary histories in large scale studies are currently limited. Here, we propose a new formalism, called EvoluCode (Evolutionary barCode), which allows the integration of different evolutionary parameters (eg, sequence conservation, orthology, synteny …) in a unifying format and facilitates the multilevel analysis and visualization of complex evolutionary histories at the genome scale. The advantages of the approach are demonstrated by constructing barcodes representing the evolution of the complete human proteome. Two large-scale studies are then described: (i) the mapping and visualization of the barcodes on the human chromosomes and (ii) automatic clustering of the barcodes to highlight protein subsets sharing similar evolutionary histories and their functional analysis. The methodologies developed here open the way to the efficient application of other data mining and knowledge extraction techniques in evolutionary systems biology studies. A database containing all EvoluCode data is available at: http://lbgi.igbmc.fr/barcodes.

International audience; Multiple comparison or alignmentof protein sequences has become a fundamental tool in many different domains in modern molecular biology, from evolutionary studies to prediction of 2D/3D structure, molecular function and inter-molecular interactions etc. By placing the sequence in the framework of the overall family, multiple alignments can be used to identify conserved features and to highlight differences or specificities. In this paper, we describe a comprehensive evaluation of many of the most popular methods for multiple sequence alignment (MSA), based on a new benchmark test set. The benchmark is designed to represent typical problems encountered when aligning the large protein sequence sets that result from today's high throughput biotechnologies. We show that alignmentmethods have significantly progressed and can now identify most of the shared sequence features that determine the broad molecular function(s) of a protein family, even for divergent sequences. However,we have identified a number of important challenges. First, the locally conserved regions, that reflect functional specificities or that modulate a protein's function in a given cellular context,are less well aligned. Second, motifs in natively disordered regions are often misaligned. Third, the badly predicted or fragmentary protein sequences, which make up a large proportion of today's databases, lead to a significant number of alignment errors. Based on this study, we demonstrate that the existing MSA methods can be exploited in combination to improve alignment accuracy, although novel approaches will still be needed to fully explore the most difficult regions. We then propose knowledge-enabled, dynamic solutions that will hopefully pave the way to enhanced alignment construction and exploitation in future evolutionary systems biology studies.

Summary: We previously developed OrthoInspector, a package incorporating an original algorithm for the detection of orthology and inparalogy relations between different species. We have added new functionalities to the package. While its original algorithm was not modified, performing similar orthology predictions, we facilitated the prediction of very large databases (thousands of proteomes), refurbished its graphical interface, added new visualization tools for comparative genomics/protein family analysis and facilitated its deployment in a network environment. Finally, we have released three online databases of precomputed orthology relationships. Availability: Package and databases are freely available at http://lbgi.fr/orthoinspector with all major browsers supported. Contact: odile.lecompte@unistra.fr Supplementary information: Supplementary data are available at Bioinformatics online.

Although the number of antiepileptic drugs (AEDs) is increasing, none displays neuroprotective or antiepileptogenic properties that could prevent status epilepticus (SE)-induced drug-resistant epilepsy. Ketogenic diet (KD) and calorie restriction (CR) are proposed as alternative treatments in epilepsy. Our goal was to assess the neuroprotective or antiepileptogenic effect of these diets in a well-characterized model of mesial temporal lobe epilepsy following initial SE induced by lithium-pilocarpine in adult rats.Seventy-five P50 male Wistar rats were fed a specific diet: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), or hypocalorie ketogenic (HK). Rats were subjected to lithium-pilocarpine SE, except six NC to constitute a control group for histology (C). Four rats per group were implanted with epidural electrodes to record electroencephalography (EEG) during SE and the next six following days. From the seventh day, the animals were video-recorded 10 h daily to determine latency to epilepsy onset. Neuronal loss in hippocampus and parahippocampal cortices was analyzed 1 month after the first spontaneous seizure.After lithium-pilocarpine injection, neither KD nor CR modified SE features or latency to epilepsy. In hippocampal layers, KD or CR exhibited a neuroprotective potential without cooperative effect. Parahippocampal cortices were not protected by the diets.The antiepileptic effect of KD and/or CR is overwhelmed by lithium-pilocarpine injection. The isolated protection of hippocampal layers induced by KD or CR or their association failed to modify the course of epileptogenesis.