Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking

Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood–brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease

The Effects of Breeding Protocol in C57BL/6J Mice on Adult Offspring Behaviour

Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10–12 days) and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH). The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM). Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI) of the acoustic startle response. We found that length of sire exposure (LSE) had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour

A New Palavela: A Temporal and Enduring Home for the Arts

In choosing a thesis project the desire was to design a facility where similar structures had not done the event justice. The sport of figure skating represented this desire well. This idea transformed into a design for an Olympic site in Turin Italy for the 2006 figure and short track speed skating. The facil¬ity will become a permanent fixture in Turin as a civic-center. Pierre Baron de Coubertin, developer of the foundation for the modern Olympic games, defined what Olympic architecture should strive to achieve, The Olympic City should captivate the visitor as a dignified and grandiose complex by monumentality and impressive appearance; a mere glance at the facilities should clearly display their double character, athletic and artistic by overlapping of functions and the unmistakable nature of the townscape; the silhouette and the landscape should as far as possible form a harmonious unit- games on green plots, buildings integrated into the landscape, interrelationship between interior space and the open space (Wimmer, 23). I chose to do an Olympic arena because of the design significance and the importance to both the host city of Turin. The Olympics is a worldwide event, but it is the host country that bears the major financial investment. Each building is looked at critically as to if and what its future use will be, at the same time as how it will function for the Olympic games. Here Coubertin has laid out the three main functions of an Olympic building: monumentality, integration between inside and out, and harmony. The design will strive to achieve these goals through the mas¬ter planning of the site and the design of an Olympic facility. While Olympic architecture in recent years has em¬braced design, and the 2006 is no different, the Palavela still does not represent Coubertin’s vision of a facility that embodies the spirit of the sport or takes into account the landscape. Turin has decided to house the skating in the Palavela, a structure created in 1961 as a commemoration to the unification of Italy. The reasoning for remodeling this building was because of its iconic status and sail-like roof structure. They have chosen to gut the building leaving only the soaring concrete roof struc¬ture. It is my opinion that the current Palavela’s roof structure is not worth saving simply because of its unique look. In fact, the structure is very similar to that of the 1968 winter Olympics’ Grenoble Ice Sports Arena. Therefore, I have chosen to use the same site, but design a new facility to better represent the sport and the city. The program for the building will cater to the needs both during and after the Olympics. The building will later become an integral part of Turin as a convention center. The program calls for a 30x60m rink with seating for 8500 people that can be transformed later into a multi functional space for activities such as a concert stage, arena for indoor sports, and a place for community fairs. The program should be versatile, similar to that of Omaha’s new Qwest Center. Coubertin was said to have found, “antique Olympia was a city of athletics, art and religious festivals. The city of athletics had a tem¬porary character, the city of art and culture a permanent one (24).” One must take note that this building and site will be just as significant to the people of Turin after the Olympics, therefore it should both represent the fluidity and dynamic nature of figure skating, but also have a lasting home for the nature of figure skating, but also have a lasting home for the arts. The three objectives are similar to that of Coubertin: -The building should be an artistic gesture of the sport with the presence of an Olympic structure, but in doing so should also fluidly meld with the overall park landscape. -The building and site should foremost become a place for gathering and activity for the community of Turin, and secondly, welcome visitors to the Olympics as a place of celebration. -The building and site should function civically paying close attention to the aesthetic of the townscape, and by doing so become a positive statement about the Olympics and Turin both inside and out

The Christopher Parkening Guitar Method, Vol. 1: The Art and Technique of the Classical Guitar

Buku ini memuat sumber yang luar biasa untuk teknik dan repertoar gitar klasik. Di dalamnya memandu semua teknik upper position (posisi atas), produksi nada, teknik tremolo, harminisasi, teknik vibrato, teknik pizzicato, dll. Selain itu memberikan pula tip-tip tentang interpretasi. Bagian pertama dalam buku ini membahas tentang berbagai teknik permainan gitar secara teori sedangkan pada bagian kedua membahas praktek teknik permainan gitar dengan memainkan lagu, misalnya potongan lagu tema karya Dowland, Bach, Scarlatti, Sor, Tarrega, dan lain-lain ditambah dengan lagu-lagu untuk permainan duet

The Christopher Parkening Guitar Method, Vol. 2: The Art and Technique of the Classical Guitar

Buku ini memuat sumber yang luar biasa untuk teknik dan repertoar gitar klasik. Di dalamnya memandu semua teknik upper position (posisi atas), produksi nada, teknik tremolo, harminisasi, teknik vibrato, teknik pizzicato, dll. Bagian pertama dalam buku ini membahas tentang berbagai teknik permainan gitar Disertai dengan repertoar-repertoar untuk dipraktekkan. Sedangkan bagian kedua dalam buku ini memuat repertoir-repertoir yang digolongkan sesuai jamannya, misalnya musik gitar jaman renaissance, barok, klasik dan romantik