Mcl-1 dynamics influence mitotic slippage and death in mitosis

Microtubule-binding drugs such as taxol are frontline treatments for a variety of cancers but exactly how they yield patient benefit is unclear. In cell culture, inhibiting microtubule dynamics prevents spindle assembly, leading to mitotic arrest followed by either apoptosis in mitosis or slippage, whereby a cell returns to interphase without dividing. Myeloid cell leukaemia-1 (Mcl-1), a pro-survival member of the Bcl-2 family central to the intrinsic apoptosis pathway, is degraded during a prolonged mitotic arrest and may therefore act as a mitotic death timer. Consistently, we show that blocking proteasome-mediated degradation inhibits taxol-induced mitotic apoptosis in a Mcl-1-dependent manner. However, this degradation does not require the activity of either APC/C-Cdc20, FBW7 or MULE, three separate E3 ubiquitin ligases implicated in targeting Mcl-1 for degradation. This therefore challenges the notion that Mcl-1 undergoes regulated degradation during mitosis. We also show that Mcl-1 is continuously synthesized during mitosis and that blocking protein synthesis accelerates taxol induced death-in-mitosis. Modulating Mcl-1 levels also influences slippage; overexpressing Mcl-1 extends the time from mitotic entry to mitotic exit in the presence of taxol, while inhibiting Mcl-1 accelerates it. We suggest that Mcl-1 competes with Cyclin B1 for binding to components of the proteolysis machinery, thereby slowing down the slow degradation of Cyclin B1 responsible for slippage. Thus, modulating Mcl-1 dynamics influences both death-in-mitosis and slippage. However, because mitotic degradation of Mcl-1 appears not to be under the control of an E3 ligase, we suggest that the notion of network crosstalk is used with caution

Influence of Parenting Practices on Eating Behaviors of Early Adolescents during Independent Eating Occasions: Implications for Obesity Prevention

Among early adolescents (10–14 years), poor diet quality along with physical inactivity can contribute to an increased risk of obesity and associated biomarkers for chronic disease. Approximately one-third of United States (USA) children in this age group are overweight or obese. Therefore, attention to factors affecting dietary intake as one of the primary contributors to obesity is important. Early adolescents consume foods and beverages during eating occasions that occur with and without parental supervision. Parents may influence eating behaviors of early adolescents during eating occasions when they are present or during independent eating occasions by engaging in practices that affect availability of foods and beverages, and through perceived normative beliefs and expectations for intake. Therefore, the purpose of this article was to describe the influence of parenting practices on eating behaviors in general and when specifically applied to independent eating occasions of early adolescents. This information may be helpful to inform parenting interventions targeting obesity prevention among early adolescents focusing on independent eating occasions

Generalized just-in-time trace compilation using a parallel task farm in a dynamic binary translator

Dynamic Binary Translation (DBT) is the key technology behind cross-platform virtualization and allows software compiled for one Instruction Set Architecture (ISA) to be executed on a processor supporting a different ISA. Under the hood, DBT is typically implemented using Just-In-Time (JIT) compilation of frequently executed program regions, also called traces. The main challenge is translating frequently executed program regions as fast as possible into highly efficient native code. As time for JIT compilation adds to the overall execution time, the JIT compiler is often decoupled and operates in a separate thread independent from the main simulation loop to reduce the overhead of JIT compilation. In this paper we present two innovative contributions. The first contribution is a generalized trace compilation approach that considers all frequently executed paths in a program for JIT compilation

Parenting practices and adolescent eating behaviors in African American families.

Parents play an important role in developing the eating behaviors of their children by adopting specific parenting practices. As the prevalence of obesity is high amongst African American adolescents, investigations into associations of specific parenting practices and adolescents' eating behaviors are essential. In this exploratory study, 14 African American parent-adolescent dyads were interviewed to characterize the influence of eight different parenting practices on the consumption of three main food categories (dairy, fruits and vegetables, and unhealthy snacks). The results revealed that authoritarian parenting practices were correlated with a higher BMI percentile in adolescents, whereas modeling and monitoring are correlated with a higher parent BMI. In addition, reasoning, monitoring, modeling, and authoritative parenting practices were associated with less unhealthy snack consumption among adolescents. Reasoning and monitoring were the only parenting practices associated with higher fruit and vegetable consumption. Finally, a significant correlation was found between eating fruits and vegetables and unhealthy snacks and the location of eating. In conclusion, different parenting practices and environmental factors may impact BMI and food consumption of African American dyads. The results of this study can be used to guide improvement in, and/or development of, nutritional education interventions considering the cultural differences of racial minorities

Managing Local Order in Conjugated Polymer Blends via Polarity Contrast

The optoelectronic landscape of conjugated polymers is intimately related to their molecular arrangement and packing, with minute changes in local order, such as chain conformation and torsional backbone order/disorder, frequently having a substantial effect on macroscopic properties. While many of these local features can be manipulated via chemical design, the synthesis of a series of compounds is often required to elucidate correlations between chemical structure and macromolecular ordering. Here, we show that blending semiconducting polymers with insulating commodity plastics enables controlled manipulation of the semiconductor backbone planarity. The key is to create a polarity difference between the semiconductor backbone and its side chains, while matching the polarity of the side chains and the additive. We demonstrate the applicability of this approach through judicious comparison of regioregular poly(3-hexylthiophene) (P3HT) with two of its more polar derivatives, namely the diblock copolymer poly(3-hexylthiophene)-block-poly(ethylene oxide) (P3HT-b-PEO) and the graft polymer poly[3-but(ethylene oxide)thiophene] (P3BEOT), as well as their blends with poly(ethylene oxide) (PEO). Proximity between polar side chains and a similarly polar additive reduces steric hindrance between individual chain segments by essentially "expelling" the side chains away from the semiconducting backbones. This process, shown to be facilitated via exposure to polar environments such as humid air/water vapor, facilitates backbone realignment toward specific chain arrangements and, in particular, planar backbone configurations