Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07: 02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1 , encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07: 02.

registered and, of these, 28% accurately reported a preregistered specific outcome. 4 The respective rates in this study (66% and 67%) are a notable improvement. This may reflect that our study assessed only high-impact-factor journals, the continued impact of policies mandating prospective trial registration, 5 and the increasing recognition of the importance of prospective trial registration by dermatology journals. 6 Discerning whether primary outcome discrepancies reflect benign variations in levels of detail or more sinister post hoc selection of results based on significance can be challenging. Of concern, previous work has associated discrepancies with an increased likelihood of larger effect sizes and statistically significant results. 7,8 Currently, the CONSORT guidelines acknowledge that changes to preregistered outcomes can occur, but that in such instances the change and rationale should be detailed in the manuscript. In the absence of an explanation, discrepancies should raise suspicion of bias.

Significance and Impact of the Study: This is the first study demonstrating antimicrobial potential of flurophoric and chromophoric metabolites extracted from bacterial biosymbionts associated with marine sponges. Our study has significant scope as Indian coastal area especially harbours vast varieties of sponges with novel secondary metabolites-producing organisms. The natural metabolites extracted from sponge-derived bacteria pave novel therapeutic remedy against various pathogens when most of them are emerged as extreme drug resistant superbugs. AbstractMarine coastal areas of India have vast diversity of sponges which harbours many endosymbiotic bacteria which are the source of many potential antimicrobial metabolites. This study focuses the screening and characterization of drug-producing bacteria symbiotically which are associated with marine sponges collected from Gulf of Mannar, South Coast India. Six different sponges were collected and they were identified on the basis of their morphology. The drug-producing isolates were screened by agar overlay method towards various clinical strains. The secondary metabolites were characterized and were found to be quinones, alkaloids, flavanoids and flavonyl glycosides. The metabolites showed significant inhibitory properties against clinical strains that were further identified as chromophoric and fluorophoric in nature. Ethyl acetate extracts of chromophore and floureophore substances showed significant inhibitory properties against Methicillin resistant Staphylococcus aureus (MRSA) and Salmonella typhi respectively. 16S rRNA gene sequencing of theses isolates revealed that chomophore-producing strain were closely related to Pseudomonas spp. RHLB12, isolated from Callyspongia spp. and floureophore-producing bacteria was related to Bacillus licheniformis T6-1 which was isolated from Haliclona spp. Hence, our study demonstrated that antimicrobial metabolites extracted from symbiotic bacteria associated with marine sponges have high therapeutic potential against many bacterial pathogens including multidrug-resistant strains.

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Subjects participated in two trial blocks of an autobiographical oddball paradigm. In the first block, 14% of the stimuli were the subject's phone number, 86% were other, meaningless numbers. Subjects responded yes or no, verbally and truthfully. In the second block, stimuli were dates, and the oddball was the subject's birthdate. Subjects again responded verbally, but dishonestly on about 50% of the trials and truthfully on the other 50%. Reaction times differed between the first and the second blocks, but not between the honest and dishonest trials of the second block. P300 amplitude was reduced in dishonest trials of the second block. Honest trials of both blocks had similar P300 amplitudes. Scaled scalp distributions were the same for honest trials of both blocks, but differed between honest and dishonest trials of the second block. There were no latency effects. The results are discussed from the viewpoint that task demand effects do not mediate the P300 differences between honest and dishonest responses.