Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs.Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor alpha (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio.These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism

Résistance et aliénation des esclaves dans les textes de Pétrone, Martial et Juvénal

RESUMEN: Los textos de Petronio, Marcial y Juvenal reflejan muchos signos de resistencia de los esclavos. Si el discurso invita a la crítica —porque es especialmente el reflejo de la preocupación de los libres—, no parece, con todo, negar que los esclavos intentaran escapar por todos los medios de la explotación acabando con las vidas de sus señores, aunque más frecuentemente huyendo o recurriendo a la holgazanería en sus tareas, al descuido o al chantaje; sin olvidar, por supuesto, los astutamente extendidos rumores que comprometían a sus señores, o el disfrute excesivo de sus vicios y pasiones. ABSTRACT: The texts of Petronius, Martial and Juvenal present many signs of resistance on the part of the slaves. If the discourse invites criticism - because it is especially the reflection of the concern of free men - it is nevertheless a fact that we see the slaves there trying by all means to escape exploitation through the murder of the master, more often by flight and more often by laziness, nonchalance and blackmail. Added to these was their cleverness in compromising their master by dangerous gossip as well as by the exploitation of his vices and passions

Résistance et aliénation des esclaves dans les textes de Pétrone, Martial et Juvénal

RESUMEN: Los textos de Petronio, Marcial y Juvenal reflejan muchos signos de resistencia de los esclavos. Si el discurso invita a la crítica —porque es especialmente el reflejo de la preocupación de los libres—, no parece, con todo, negar que los esclavos intentaran escapar por todos los medios de la explotación acabando con las vidas de sus señores, aunque más frecuentemente huyendo o recurriendo a la holgazanería en sus tareas, al descuido o al chantaje; sin olvidar, por supuesto, los astutamente extendidos rumores que comprometían a sus señores, o el disfrute excesivo de sus vicios y pasiones

A bilateral comparison of optical glass refractive index between NMIJ and INRiM for the validation of the measuring systems

A bilateral comparison of refractive index measurements between the National Metrology Institute of Japan (NMIJ) and the Istituto Nazionale di Ricerca Metrologica (INRiM) was carried out in 2008. Each laboratory developed a measurement system based on different principles. NMIJ’s system was based on the interferometric technique and INRiM’s system was based on a modified method of the traditional refractive technique. A comparison using a prism-shaped glass made of OHARA BSL7Y was carried out in order to evaluate the newly developed methods and confirm the consistency of the results. The details of the comparison artefacts, measurement conditions and uncertainty factors and their degrees of freedom of each laboratory are described here. The measurement results for the glass at 633 nm at 20 ◦C and 23 ◦C are within each laboratory’s claimed expanded uncertainty (coverage factor k = 2) which was of the order of 10−6. The agreement between the two different measurement approaches shows that both systems can be used to obtain accurate measurements