We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.

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Mutations in the human cellular retinaldehyde binding protein (CRALBP) gene cause retinal pathology. To understand the molecular basis of impaired CRALBP function, we have characterized human recombinant CRALBP containing the disease causing mutations R233W or M225K. Protein structures were verified by amino acid analysis and mass spectrometry, retinoid binding properties were evaluated by UV-visible and fluorescence spectroscopy and substrate carrier functions were assayed for recombinant 11-cis-retinol dehydrogenase (rRDH5). The M225K mutant was less soluble than the R233W mutant and lacked retinoid binding capability and substrate carrier function. In contrast, the R233W mutant exhibited solubility comparable to wild type rCRALBP and bound stoichiometric amounts of 11-cis-and 9-cis-retinal with at least 2-fold higher affinity than wild type rCRALBP. Holo-R233W significantly decreased the apparent affinity of rRDH5 for 11-cis-retinoid relative to wild type rCRALBP. Analyses by heteronuclear single quantum correlation NMR demonstrated that the R233W protein exhibits a different conformation than wild type rCRALBP, including a different retinoid-binding pocket conformation. The R233W mutant also undergoes less extensive structural changes upon photoisomerization of bound ligand, suggesting a more constrained structure than that of the wild type protein. Overall, the results show that the M225K mutation abolishes and the R233W mutation tightens retinoid binding and both impair CRALBP function in the visual cycle as an 11-cisretinol acceptor and as a substrate carrier.Mutations in the human gene RLBP1 encoding the cellular retinaldehyde-binding protein (CRALBP) 1 cause retinal pathology and have been associated with autosomal recessive retinitis pigmentosa (1), Bothnia dystrophy (2, 3), retinitis punctata albescens (4), fundus albipunctatus (5), and Newfoundland rod-cone dystrophy (6). These diseased phenotypes are all characterized by photoreceptor degeneration and night blindness (delayed dark adaptation) but differ in age of onset, rate of progression, and severity. The molecular basis for the clinical differences in these related retinal dystrophies is not well understood and no effective therapies exist for the pathology resulting from impaired CRALBP function.CRALBP is an abundant, 36-kDa protein in the cytosol of the retinal pigment epithelium (RPE) and Mü ller cells of the retina where it carries endogenous 11-cis-retinol and 11-cis-retinal (7). The CRALBP ligand binding cavity is mapped in the accompanying report (8). In vivo studies (9) show that CRALBP serves as a major 11-cis-retinol acceptor in the isomerization step of the visual cycle (7, 10, 11), stimulating the enzymatic isomerization of all-trans-to 11-cis-retinol in the rod visual cycle. However, CRALBP appears to function within an RPE protein complex (12) and to serve multiple functions. In vitro, CRALBP facilitates the oxidation of 11-cis-retinol to 11-cisretinal by 11-cis-retinol dehydrogenase (12, 13), retards 11-cisretinol esterification...

Premature ovarian failure (POF) is characterized by hypergonadotropic hypogonadism and amenorrhea before the age of 40. The condition has a heterogeneous background but genetic factors are demonstrated by the occurrence of familial cases. We identified a mother and daughter with POF both of whom carry an X;autosome translocation [t(X;11)(q24;q13)]. RNA expression studies of genes flanking the X-chromosome breakpoint revealed that both patients have reduced expression levels of the gene Progesterone Receptor Membrane Component-1 (PGRMC1). Mutation screening of 67 females with idiopathic POF identified a third patient with a missense mutation (H165R) located in the cytochrome b5 domain of PGRMC1. PGRMC1 mediates the anti-apoptotic action of progesterone in ovarian cells and it acts as a positive regulator of several cytochrome P450 (CYP)-catalyzed reactions. The CYPs are critical for intracellular sterol metabolism, including biosynthesis of steroid hormones. We show that the H165R mutation associated with POF abolishes the binding of cytochrome P450 7A1 (CYP7A1) to PGRMC1. In addition, the missense mutation attenuates PGRMC1's ability to mediate the anti-apoptotic action of progesterone in ovarian cells. These findings suggest that mutant or reduced levels of PGMRC1 may cause POF through impaired activation of the microsomal cytochrome P450 and increased apoptosis of ovarian cells.

Loss of chromosomes is the primary event in near-haploid and low hypodiploid acute lymphoblastic leukemia. Link to publication Citation for published version (APA): Safavi, S., Forestier, E., Golovleva, I., Barbany, G., Hansén Nord, K., Moorman, A. V., ... Paulsson, K. (2013). Loss of chromosomes is the primary event in near-haploid and low hypodiploid acute lymphoblastic leukemia. Leukemia, 27(1), 248-250. DOI: 10.1038/leu.2012 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal The majority of patients with hypodiploid ALL have 45 chromosomes; near-haploidy and HoL are very rare, comprising less than 1% of B-cell precursor (BCP) ALL. 2,4 Near-haploid ALL is seen primarily in children and adolescents, although some adult cases have been reported, whereas HoL occurs at all ages. 4 Cases usually have an early pre-B