Modulation of Cellular Cholesterol and Its Effect on Cornified Envelope Formation in Cultured Human Epidermal Keratinocytes

When cultured human epidermal keratinocytes (NHK) reach confluence they start to differentiate and an increase in the total cellular cholesterol content is observed. This increase parallels the appearance of a characteristic feature of terminal keratinocyte differentiation, the spontaneous formation of cornified envelopes (CE). Synthesis of CE is catalyzed by the plasma membrane-associated transglutaminase (TGm). Supplementation of the medium with inhibitors of cholesterologenesis suppressed increase in cholesterol levels and CE formation but did not interfere with TGm expression or TGm activity. Modulation of the plasma membrane cholesterol-phospholipid ratio of confluent NHK cultures using either pure phospholipid liposomes or liposomes enriched in cholesterol strongly affected spontaneous CE formation. Pure phospholipid liposomes completely inhibited CE formation, whereas cholesterol-enriched liposomes ensured envelope formation, even in the presence of inhibitors of cholesterol synthesis. From these results we conclude that in differentiating NHK an increase in the cellular cholesterol level is part of the differentiation program and is essential for the spontaneous CE formation

Half-Dead Colonies of Montastraea Annularis Release Viable Gametes On A Degraded Reef In The Us Virgin Islands

This article contributes to scholarship on Afroeurope by investigating the intersection of blackness, Africanness, and Europeanness in everyday discourses and social practices in the Netherlands and Italy. We examine how young African-descended Europeans are forging new ways of being both African and European through practices of self-making, which should be understood against both the historical background of colonialism and the contemporary politics of othering. Such practices take on an urgency for these youth, often encompassing a reinvention of Africanness and/or blackness as well as a challenge to dominant, exclusionary understandings of Europeanness. Comparing Afro-Dutch and Afro-Italian modes of self-making, centred on African heritage and roots, we discuss: 1) the emergence of a transnational, Afroeuropean imaginary, distinguished from both white Europe and African-American formations; and 2) the diversity of Afroeuropean modes of self-making, all rooted in distinct histories of colonialism, slavery, and immigration, and influenced by global formations of Africanness and blackness. These new Afro and African identities advanced by young Europeans do not turn away from Europeanness (as dominant identity models would assume: the more African, the less European), nor simply add to Europeanness (“multicultural” identities), nor even mix with Europeanness (“hybrid” identities), but are in and of themselves European

A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis

The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis . It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed

Development of crystalline inclusions (“ergosterol crystals”) in Neurospora crassa

Development of crystalline inclusions (“ergosterol crystals”) in “snowflake”, a morphological mutant of Neurospora crassa has been examined. The inclusions which arise in membranebound organelles appear as electron dense deposits, increase in size, and occupy nearly all the space within the organelle at maturity. The presence of catalase activity in the organelle was not detected using cytochemical procedures employing diaminobenzidine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41731/1/709_2005_Article_BF01275681.pd

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

The oxidation of a borane intermediate by PFC provides a convenient synthesis of 24-ketolanosteryl acetate