Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease

Oxidative damage control in a human (mini-) organ: Nrf2 activation protects against oxidative stress-induced hair growth inhibition

The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of Nrf2, the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ, human scalp hair follicles (HFs). Microarray and qPCR analysis of human HFs following Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, ROS clearance, the pentose phosphate pathway and glutathione homeostasis. Nrf2 knockdown (siRNA) in cultured human HFs confirmed the regulation of key Nrf2 target genes (i.e. HO-1, NQO1, GSR, GCLC, ABCC1, PRDX1). Importantly, Nrf2 activation significantly reduced ROS levels and associated lipid peroxidation. Nrf2 pre-activation reduced oxidative stress-stimulated (H2O2 or menadione) premature catagen and hair growth inhibition, significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the ROS-induced reduction in proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e. scalp HFs) against redox insult

Mining for significant execution profiles for software assessment -

Thesis. M.E. American University of Beirut. Department of Electrical and Computer Engineering, 2014. ET:6009Advisor : Prof. Wassim Masri, Associate Professor, Electrical and Computer Engineering ; Committee members: Prof. Hazem Hajj, Associate Professor, Electrical and Computer Engineering ; Prof. Fadi Zaraket, Assistant Professor, Electrical and Computer Engineering.Includes bibliographical references (leaves 63-66)The interest in applying data mining and statistical techniques to solve software analysis problems has increased tremendously in recent years. Researchers have presented numerous techniques that mine and analyze execution profiles to assist software testing, fault localization, and program comprehension. Previous empirical studies have shown that the effectiveness of such techniques is likely to be impacted by the type of the profiled program elements. This work further studies the impact of the characteristics of execution profiles by focusing on their size; noting that a typical profile comprises a large number of elements, in the order of thousands or higher. Specifically, we devised six reduction techniques and comparatively evaluated them by measuring the following: 1) reduction rate; 2) information loss; 3) impact on the quality of cluster analysis, using various metrics; 4) cost of reduction; and 5) impact on two software analysis techniques, namely, cluster-based test suite minimization and profile-based online intrusion detection. Our results were promising as: a) the average reduction rate ranged from 92percent to 98percent; b) three techniques were lossless and three were slightly lossy; c) the quality of cluster analysis was not deteriorated; d) the cost of reduction was not very significant; and e) reducing execution profiles noticeably benefited the two software analysis techniques in our experiments

The potential of nanomedicine therapies to treat neovascular disease in the retina

Neovascular disease in the retina is the leading cause of blindness in all age groups. Thus, there is a great need to develop effective therapeutic agents to inhibit and prevent neovascularization in the retina. Over the past decade, anti-VEGF therapeutic agents have entered the clinic for the treatment of neovascular retinal disease, and these agents have been effective for slowing and preventing the progression of neovascularization. However, the therapeutic benefits of anti-VEGF therapy can be diminished by the need for prolonged treatment regimens of repeated intravitreal injections, which can lead to complications such as endophthalmitis, retinal tears, and retinal detachment. Recent advances in nanoparticle-based drug delivery systems offer the opportunity to improve bioactivity and prolong bioavailability of drugs in the retina to reduce the risks associated with treating neovascular disease. This article reviews recent advances in the development of nanoparticle-based drug delivery systems which could be utilized to improve the treatment of neovascular disease in the retina

“PASSARINHEIROS” – UMA ETNOGRAFIA SOBRE PESSOAS & PÁSSAROS DA ILHA DE FLORIANÓPOLIS.

TCC (graduação) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Curso de Ciências Sociais.O trabalho a seguir trás depoimentos e cenas de encontros com criadores de pássaros canoros em um documentário gravado na Ilha de Florianópolis – Santa Catarina. Propõe obter reflexões e conhecimentos sobre esta tradição através do ponto de vista e opiniões dos próprios criadores, suas estórias e experiências sobre pássaros, e mostrando os espaços de convivência entre eles.The following work brings testimony and scenes of encounters with breeders of singing birds in a documentary recorded on the Island of Florianópolis - Santa Catarina. It proposes to obtain reflections and knowledge on this tradition through the point of view and opinions of the breeders themselves, their stories and experiences about birds, and showing the spaces of coexistence between them

Male pattern hair loss: can developmental origins explain the pattern?

Male pattern hair loss (MPHL), also referred to as male androgenetic alopecia (AGA) is the most common type of non-scarring progressive hair loss, with 80% of men suffering from this condition in their lifetime. In MPHL, the hair line recedes to a specific part of the scalp which cannot be accurately predicted. Hair is lost from the front, vertex, and the crown, yet temporal and occipital follicles remain. The visual effect of hair loss is due to hair follicle miniaturisation, where terminal hair follicles become dimensionally smaller. Miniaturisation is also characterised by a shortening of the growth phase of the hair cycle (anagen), and a prolongation of the dormant phase (kenogen). Together, these changes result in the production of thinner and shorter hair fibres, referred to as miniaturised or vellus hairs. It remains unclear why miniaturisation occurs in this specific pattern, with frontal follicles susceptible while occipital follicles remain in a terminal state. One main factor we believe to be at play, which will be discussed in this viewpoint, is the developmental origin of the skin and hair follicle dermis on different regions of the scalp

Axillary Artery Pseudoaneurysm Following Percutaneous Transaxillary Access for Impella Device Placement during Percutaneous Coronary Intervention

Percutaneous transaxillary access is currently considered an acceptable alternative to transfemoral approach for large-bore access, especially in the setting of hostile iliofemoral arteries. Few published reports exist concerning complications of upper extremity access. We describe development of an axillary artery pseudoaneurysm and its management following transaxillary access. (Level of Difficulty: Advanced.