Temporal and spatial variations in the parasitoid complex of the horse chestnut leafminer during its invasion of Europe

The enemy release hypothesis posits that the initial success of invasive species depends on the scarcity and poor adaptation of native natural enemies such as predators and parasitoids. As for parasitoids, invading hosts are first attacked at low rates by a species-poor complex of mainly generalist species. Over the years, however, parasitoid richness may increase either because the invading host continuously encounters new parasitoid species during its spread (geographic spread-hypothesis) or because local parasitoids need different periods of time to adapt to the novel host (adjustment-hypothesis). Both scenarios should result in a continuous increase of parasitoid richness over time. In this study, we reconstructed the development of the hymenopteran parasitoid complex of the invasive leafminer Cameraria ohridella (Lepidoptera, Gracillariidae). Our results show that the overall parasitism rate increases as a function of host residence time as well as geographic and climatic factors, altogether reflecting the historic spread of C. ohridella. The same variables also explain the individual parasitism rates of several species in the parasitoid complex, but fail to explain the abundance of others. Evidence supporting the “geographic spread-hypothesis” was found in the parasitism pattern of Cirrospilus talitzkii (Hymenoptera, Eulophidae), while that of Pediobius saulius, another eulophid, indicated an increase of parasitism rates by behavioral, phenological or biological adjustments. Compared to fully integrated host-parasitoid associations, however, parasitism rates of C. ohridella are still very low. In addition, the parasitoid complex lacks specialists, provided that the species determined are valid and not complexes of cryptic (and presumably more specialized) species. Probably, the adjustment of specialist parasitoids requires more than a few decades, particularly to invaders which establish in ecological niches free of native hosts, thus eliminating any possibility of recruitment of pre-adapted parasitoids

Epithelial maturation and molecular biology of oral HPV

Human papillomavirus (HPV) is widespread and can cause latent infection in basal cells, with low HPV DNA copy-number insufficient for transmission of infection; can cause subclinical infection that is active but without clinical signs; or can cause clinical infection leading to benign, potentially malignant or malignant lesions. The HPV cycle is influenced by the stage of maturation of the infected keratinocytes, and the production of virions is restricted to the post-mitotic suprabasal epithelial cells where all the virus genes are expressed

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with non-Syndromic Hearing impairment and auditory neuropathy.

Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene. Cohorts of 708 Spanish, 83 Colombian, and 30 Argentinean unrelated subjects with autosomal recessive NSHI were screened for the common p.Gln829X mutation. In compound heterozygotes, the second mutant allele was identified by DNA sequencing. In total, 23 Spanish, two Colombian and two Argentinean subjects were shown to carry two mutant alleles of OTOF. Of these, one Colombian and 13 Spanish subjects presented with auditory neuropathy. In addition, a cohort of 20 unrelated subjects with a diagnosis of auditory neuropathy, from several countries, was screened for mutations in OTOF by DNA sequencing. A total of 11 of these subjects were shown to carry two mutant alleles of OTOF. In total, 18 pathogenic and four neutral novel alleles of the OTOF gene were identified. Haplotype analysis for markers close to OTOF suggests a common founder for the novel c.2905_2923delinsCTCCGAGCGCA mutation, frequently found in Argentina. Our results confirm that mutation of the OTOF gene correlates with a phenotype of prelingual, profound NSHI, and indicate that OTOF mutations are a major cause of inherited auditory neuropathy