Lipid uptake in chronic lymphocytic leukemia.

Many cancers rely on glucose as an energy source, but it is becoming increasingly apparent that some cancers use alternate substrates to fuel their proliferation. Chronic lymphocytic leukaemia (CLL) is one such cancer. Through the use of flow cytometry and confocal microscopy, low levels of glucose uptake were observed in the OSU-CLL and HG3 CLL cell lines relative to highly glucose-avid Raji cells (Burkitt's lymphoma). Glucose uptake in CLL cells correlated with low expression of the GLUT1 and GLUT3 receptors. In contrast, both CLL cell lines and primary CLL cells, but not healthy B cells, were found to rapidly internalise medium- and long-chain, but not short-chain, fatty acids (FAs). Differential FA uptake was also observed in primary cells taken from patients with unmutated immunoglobulin heavy variable chain usage (IGHV) compared with patients with mutated IGHV. Delipidation of serum in the culture medium slowed the proliferation and significantly reduced the viability of OSU-CLL and HG3 cells, effects that were partially reversed by supplementation with a chemically defined lipid concentrate. These observations highlight the potential importance of FAs in the pathogenesis of CLL and raise the possibility that targeting FA utilisation may represent a novel therapeutic and prognostic approach in this disease.

Defining and Measuring Students' Interest in Biology: An Analysis of the Biology Education Literature.

Understanding how students develop biology interests and the roles interest plays in biology contexts could help instructors and researchers to increase science, technology, engineering, and mathematics students' motivation and persistence. However, it is currently unclear how interest has been defined or measured in the biology education research literature. We analyzed this body of literature to determine how interest has been defined and used by the biology education research community. Specifically, we determined the extent to which previously published work drew on theories that conceptualize interest. Further, we identified studies that measured student interest in biology and characterized the types of measures used. Our findings indicate that biology education researchers typically describe interest as a relationship involving positive feelings between an individual and a physical object, activity, or topic of focus. We also found that interest is often not defined, theories involving interest are not often consulted, and the most common measures of interest only assess a single aspect of the construct. On the basis of these results, we make suggestions for future research seeking to examine biology students' interest. We hope that this analysis can serve as tool for biology educators to improve their own investigations of students' interest and measure outcomes of interest-generating educational activities.

Students Who Fail to Achieve Predefined Research Goals May Still Experience Many Positive Outcomes as a Result of CURE Participation.

Course-based undergraduate research experiences (CUREs) provide students opportunities to engage in research in a course. Aspects of CURE design, such as providing students opportunities to make discoveries, collaborate, engage in relevant work, and iterate to solve problems are thought to contribute to outcome achievement in CUREs. Yet how each of these elements contributes to specific outcomes is largely unexplored. This lack of understanding is problematic, because we may unintentionally underemphasize important aspects of CURE design that allow for achievement of highly valued outcomes when designing or teaching our courses. In this work, we take a qualitative approach and leverage unique circumstances in two offerings of a CURE to investigate how these design elements influence outcome achievement. One offering experienced many research challenges that increased engagement in iteration. This level of research challenge ultimately prevented achievement of predefined research goals. In the other offering, students experienced fewer research challenges and ultimately achieved predefined research goals. Our results suggest that, when students encounter research challenges and engage in iteration, they have the potential to increase their ability to navigate scientific obstacles. In addition, our results suggest roles for collaboration and autonomy, or directing one's own work, in outcome achievement.

ER contact sites define the position and timing of endosome fission.

Endocytic cargo and Rab GTPases are segregated to distinct domains of an endosome. These domains maintain their identity until they undergo fission to traffic cargo. It is not fully understood how segregation of cargo or Rab proteins is maintained along the continuous endosomal membrane or what machinery is required for fission. Endosomes form contact sites with the endoplasmic reticulum (ER) that are maintained during trafficking. Here, we show that stable contacts form between the ER and endosome at constricted sorting domains, and free diffusion of cargo is limited at these positions. We demonstrate that the site of constriction and fission for early and late endosomes is spatially and temporally linked to contact sites with the ER. Lastly, we show that altering ER structure and dynamics reduces the efficiency of endosome fission. Together, these data reveal a surprising role for ER contact in defining the timing and position of endosome fission.

Endoplasmic reticulum-endosome contact increases as endosomes traffic and mature.

The endosomal pathway is responsible for plasma membrane cargo uptake, sorting, and, in many cases, lysosome targeting. Endosome maturation is complex, requiring proper spatiotemporal recruitment of factors that regulate the size, maturity, and positioning of endosomal compartments. In animal cells, it also requires trafficking of endosomes on microtubules. Recent work has revealed the presence of contact sites between some endosomes and the endoplasmic reticulum (ER). Although these contact sites are believed to have multiple functions, the frequency, dynamics, and physical attributes of these contacts are poorly understood. Here we use high-resolution three-dimensional electron microscopy to reveal that ER tubules wrap around endosomes and find that both organelles contact microtubules at or near membrane contact sites. As endosomes traffic, they remain bound to the ER, which causes the tubular ER to rearrange its structure around dynamic endosomes at contact sites. Finally, as endosomes transition through steps of maturation, they become more tightly associated with the ER. The major implication of these results is that endosomes mature and traffic while coupled to the ER membrane rather than in isolation.

Endoplasmic reticulum-mitochondria contacts: function of the junction.

The most well-characterized organelle contact sites are those between the endoplasmic reticulum (ER) and mitochondria. Increased understanding is being gained of how ER-mitochondria contact sites are organized and which factors converge at this interface, some of which may provide a tethering function. The role of the ER-mitochondria junction in coordinating the functions of these two organelles is also becoming clearer, and it has been shown to be involved in the regulation of lipid synthesis, Ca(2+) signalling and the control of mitochondrial biogenesis and intracellular trafficking.