Janus kinase inhibitors may be an effective treatment to reduce skin depigmentation in vitiligo

A clinical decision report appraising Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, Turkowski Y, Sheth V, Huang V, Au SC, Kachuk C, Dumont N, Gottlieb AB, Rosmarin D. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol. 2017 Jun;76(6):1054-1060.e1. https://doi.org/10.1016/j.jaad.2017.02.049 for a patient with worsening vitiligo

Mechanisms of ATP release and signalling in the blood vessel wall

The nucleotide adenosine 5′-triphosphate (ATP) has classically been considered the cell's primary energy currency. Importantly, a novel role for ATP as an extracellular autocrine and/or paracrine signalling molecule has evolved over the past century and extensive work has been conducted to characterize the ATP-sensitive purinergic receptors expressed on almost all cell types in the body. Extracellular ATP elicits potent effects on vascular cells to regulate blood vessel tone but can also be involved in vascular pathologies such as atherosclerosis. While the effects of purinergic signalling in the vasculature have been well documented, the mechanism(s) mediating the regulated release of ATP from cells in the blood vessel wall and circulation are now a key target of investigation. The aim of this review is to examine the current proposed mechanisms of ATP release from vascular cells, with a special emphasis on the transporters and channels involved in ATP release from vascular smooth muscle cells, endothelial cells, circulating red blood cells, and perivascular sympathetic nerves, including vesicular exocytosis, plasma membrane F1/F0-ATP synthase, ATP-binding cassette (ABC) transporters, connexin hemichannels, and pannexin channel

The Influence of Parental Alcoholism on Parent–Adolescent Relationships From Adolescence Into Emerging Adulthood: A Qualitative Inquiry

Exposure to parental alcoholism can inhibit a child’s ability to become a successfully functioning young adult. Based on qualitative interviews, this study provides a deeper understanding of how those parent–adolescent relationships are associated with risky internalizing and externalizing behaviors. This qualitative study explores the lives of 13 young adult children of alcoholics (ACOAs) and provides a unique perspective through an adaptive developmental approach by evaluating emerging adults who were ACOAs and successfully functioning. Compelling findings emerged with respect to how young adults define alcoholism and being a child of alcoholism and how the parent–adolescent relationship adapts in the unstable environment associated with family alcoholism. Salient findings revealed that when emotional and physical detachment from a parent’s alcoholic behaviors in addition to an acceptance that those behaviors are not the adolescent’s responsibility, individuals gained better control of their environment aiding them in becoming healthy, functioning young adults

Phylogeography and genetic diversity of a widespread Old World butterfly, Lampides boeticus (Lepidoptera: Lycaenidae)

<p>Abstract</p> <p>Background</p> <p>Evolutionary genetics provides a rich theoretical framework for empirical studies of phylogeography. Investigations of intraspecific genetic variation can uncover new putative species while allowing inference into the evolutionary origin and history of extant populations. With a distribution on four continents ranging throughout most of the Old World, <it>Lampides boeticus </it>(Lepidoptera: Lycaenidae) is one of the most widely distributed species of butterfly. It is placed in a monotypic genus with no commonly accepted subspecies. Here, we investigate the demographic history and taxonomic status of this widespread species, and screen for the presence or absence of the bacterial endosymbiont <it>Wolbachia</it>.</p> <p>Results</p> <p>We performed phylogenetic, population genetic, and phylogeographic analyses using 1799 bp of mitochondrial sequence data from 57 specimens collected throughout the species' range. Most of the samples (>90%) were nearly genetically identical, with uncorrected pairwise sequence differences of 0 – 0.5% across geographic distances > 9,000 km. However, five samples from central Thailand, Madagascar, northern Australia and the Moluccas formed two divergent clades differing from the majority of samples by uncorrected pairwise distances ranging from 1.79 – 2.21%. Phylogenetic analyses suggest that <it>L. boeticus </it>is almost certainly monophyletic, with all sampled genes coalescing well after the divergence from three closely related taxa included for outgroup comparisons. Analyses of molecular diversity indicate that most <it>L. boeticus </it>individuals in extant populations are descended from one or two relatively recent population bottlenecks.</p> <p>Conclusion</p> <p>The combined analyses suggest a scenario in which the most recent common ancestor of <it>L. boeticus </it>and its sister taxon lived in the African region approximately 7 Mya; extant lineages of <it>L. boeticus </it>began spreading throughout the Old World at least 1.5 Mya. More recently, expansion after population bottlenecks approximately 1.4 Mya seem to have displaced most of the ancestral polymorphism throughout its range, though at least two early-branching lineages still persist. One of these lineages, in northern Australia and the Moluccas, may have experienced accelerated differentiation due to infection with the bacterial endosymbiont <it>Wolbachia</it>, which affects reproduction. Examination of a haplotype network suggests that Australia has been colonized by the species several times. While there is little evidence for the existence of morphologically cryptic species, these results suggest a complex history affected by repeated dispersal events.</p

Sharing a Top Manager’s Experience with the Next Generation: The Use of Electronic Discussions and Short Video Fragments in Teaching

In: A.J. Kallenberg and M.J.J.M. van de Ven (Eds), 2002, The New Educational Benefits of ICT in Higher Education: Proceedings. Rotterdam: Erasmus Plus BV, OECR ISBN 90-9016127-9This paper presents an effective educational method to transfer managerial knowledge to students. This method consists among other of online discussions between small groups of students and video clips of lectures. The set-up of the course and the ICT-tool used in the course were evaluated for two years through a questionnaire among the students. The results show that the applied e-learning concept is highly appreciated and serves as an effective tool to exchange knowledge

Velocity and processivity of helicase unwinding of double-stranded nucleic acids

Helicases are molecular motors which unwind double-stranded nucleic acids (dsNA) in cells. Many helicases move with directional bias on single-stranded (ss) nucleic acids, and couple their directional translocation to strand separation. A model of the coupling between translocation and unwinding uses an interaction potential to represent passive and active helicase mechanisms. A passive helicase must wait for thermal fluctuations to open dsNA base pairs before it can advance and inhibit NA closing. An active helicase directly destabilizes dsNA base pairs, accelerating the opening rate. Here we extend this model to include helicase unbinding from the nucleic-acid strand. The helicase processivity depends on the form of the interaction potential. A passive helicase has a mean attachment time which does not change between ss translocation and ds unwinding, while an active helicase in general shows a decrease in attachment time during unwinding relative to ss translocation. In addition, we describe how helicase unwinding velocity and processivity vary if the base-pair binding free energy is changed.Comment: To appear in special issue on molecular motors, Journal of Physics - Condensed Matte

Helicase activity promoted through dynamic interactions between a ssDNA translocase and a diffusing SSB protein

Replication protein A (RPA) is a eukaryotic single-stranded (ss) DNA-binding (SSB) protein that is essential for all aspects of genome maintenance. RPA binds ssDNA with high affinity but can also diffuse along ssDNA. By itself, RPA is capable of transiently disrupting short regions of duplex DNA by diffusing from a ssDNA that flanks the duplex DNA. Using single-molecule total internal reflection fluorescence and optical trapping combined with fluorescence approaches, we show tha

Assessing the importance of a self-generated detachment process in river biofilm models

1. Epilithic biofilm biomass was measured for 14 months in two sites, located up- and downstream of the city of Toulouse in the Garonne River (south-west France). Periodical sampling provided a biomass data set to compare with simulations from the model of Uehlinger, Bürher and Reichert (1996: Freshwater Biology, 36, 249–263.), in order to evaluate the impact of hydraulic disturbance. 2. Despite differences in application conditions (e.g. river size, discharge, frequency of disturbance), the base equation satisfactorily predicted biomass between low and high water periods of the year, suggesting that the flood disturbance regime may be considered a universal mechanism controlling periphyton biomass. 3. However modelling gave no agreement with biomass dynamics during the 7-month long low water period that the river experienced. The influence of other biomass-regulating factors (temperature, light and soluble reactive phosphorus) on temporal biomass dynamics was weak. 4. Implementing a supplementary mechanism corresponding to a temperature-dependent self-generated loss because of heterotrophic processes allowed us to accurately reproduce the observed pattern: a succession of two peaks. This case study suggests that during typical summer low water periods (flow stability and favourable temperature) river biofilm modelling requires self-generated detachment to be considered

Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD

The helicase PcrA unwinds DNA during asymmetric replication of plasmids, acting with an initiator protein, in our case RepD. Detailed kinetics of PcrA activity were measured using bulk solution and a single-molecule imaging technique to investigate the oligomeric state of the active helicase complex, its processivity and the mechanism of unwinding. By tethering either DNA or PcrA to a microscope coverslip surface, unwinding of both linear and natural circular plasmid DNA by PcrA/RepD was followed in real-time using total internal reflection fluorescence microscopy. Visualization was achieved using a fluorescent single-stranded DNA-binding protein. The single-molecule data show that PcrA, in combination with RepD, can unwind plasmid lengths of DNA in a single run, and that PcrA is active as a monomer. Although the average rate of unwinding was similar in single-molecule and bulk solution assays, the single-molecule experiments revealed a wide distribution of unwinding speeds by different molecules. The average rate of unwinding was several-fold slower than the PcrA translocation rate on single-stranded DNA, suggesting that DNA unwinding may proceed via a partially passive mechanism. However, the fastest dsDNA unwinding rates measured in the single-molecule unwinding assays approached the PcrA translocation speed measured on ssDNA