A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell.

In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging.DOI: http://dx.doi.org/10.7554/eLife.01883.001

Effects of Foot Orthoses on Skeletal Motion During Running

Objective. To quantify the effects of medial foot orthoses on skeletal movements of the calcaneus and tibia during the stance phase in running. Design. Kinematic effects of medial foot orthoses (anterior, posterior, no support) were tested using skeletal (and shoe) markers at the calcaneus and tibia. Background. Previous studies using shoe and skin markers concluded that medially placed orthoses control/reduce foot eversion and tibial rotation. However, it is currently unknown if such orthoses also affect skeletal motion at the lower extremities. Methods. Intracortical Hofman pins with reflective marker triads were inserted under standard local anesthetic into the calcaneus and tibia of five healthy male subjects. The three-dimensional tibiocalcaneal rotations were determined using a joint coordinate system approach. Eversion (skeletal and shoe) and tibial rotation were calculated to study the foot orthoses effects. Results. Orthotic effects on eversion and tibial rotations were found to be small and unsystematic over all subjects. Differences between the subjects were significantly larger (pp\u3c0.05). Conclusions. This in vivo study showed that medially placed foot orthoses did not change tibiocalcaneal movement patterns substantially during the stance phase of running. Relevance Orthoses may have only small kinematic effects on the calcaneus and tibia (measured with bone pins) as well as on the shoes (measured with shoe markers) during running of normal subjects. Present results showed that orthotic effects were subject specific and unsystematic across conditions. It is speculated that orthotic effects during the stance phase of running may be mechanical as well as proprioceptive

Illegal Substance Use among Italian High School Students: Trends over 11 Years (1999–2009)

Purpose: To monitor changes in habits in drug use among Italian high school students. Methods: Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out in Italy annually for 11 years (1999-2009) with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT), use in the last year (LY), use in the last 30 days (LM), frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. Results: When the time-averaged value was considered, cannabis (30% LT) was the most, and heroin the least (2%) frequently used, with cocaine (5%), hallucinogens (2%) and stimulants (2%) in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7-2.4, p,0.05), less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2-1.5, p,0.05). Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. Conclusions: Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.-

Sarcomere dynamics during muscular contraction and their implications to muscle function

ISSN:0142-4319ISSN:1573-265