Bax limits adult neural stem cell persistence through caspase and IP3 receptor activation

Neural stem cells in the mammalian brain persist and are functional well into adulthood. There is, however, little insight into mechanisms that control adult neural stem cell survival. Mice deficient in the proapoptotic molecule Bax exhibit increased numbers of multipotent progenitor cells in the adult subventricular zone. In vitro, these progenitors behave as neural stem cells and utilize Bax and caspase activation to direct cell death. We demonstrate that the predominate mechanism underlying caspase and Bax-mediated adult neural stem cell death lies in the modulation of calcium flux through interaction with the IP3 receptor.     

A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase.

Insulin receptor-related receptor (IRR), an orphan receptor in the insulin receptor (IR) family of receptor tyrosine kinases, is primarily localized to neural crest-derived sensory neurons during embryonic development. Expression of IRR closely resembles that of the nerve growth factor receptor, TrkA. To analyze the signaling properties and function of IRR in PC12 cells, a TrkB/IRR hybrid receptor was used. In contrast to IR activation, brain-derived neurotrophic growth factor-mediated activation of the TrkB/IRR receptor resulted in differentiation rather than proliferation. Analysis of cytoplasmic substrates activated by the TrkB/IRR receptor indicates a signaling pathway similar to that of the IR. Mutagenesis studies further show that only TrkB/IRR receptors able to phosphorylate mitogen-activated protein kinase elicit a differentiation response. Our analysis indicates that prolonged kinetics of mitogen-activated protein kinase activation mediated by the TrkB/IRR chimeric receptor correlates with induction to differentiate.     

Improved monitoring of oriental fruit moth (Lepidoptera: Tortricidae) with terpinyl acetate plus acetic acid membrane lures

Male and female moth catches of Grapholita molesta (Busck) in traps were evaluated in stone and pome fruit orchards untreated or treated with sex pheromones for mating disruption in Uruguay, Argentina, Chile, USA, and Italy from 2015 to 2017. Trials evaluated various blends loaded into either membrane cup lures or septa. Membrane lures were loaded with terpinyl acetate (TA), acetic acid (AA) and (Z)‐3‐hexenyl acetate alone or in combinations. Two septa lures were loaded with either the three‐component sex pheromone blend for G. molesta alone or in combination with codlemone (2‐PH), the sex pheromone of Cydia pomonella (L). A third septum lure included the combination sex pheromone blend plus pear ester, (E,Z)‐2,4‐ethyl decadienoate (2‐PH/PE), and a fourth septum was loaded with only β‐ocimene. Results were consistent across geographical areas showing that the addition of β‐ocimene or (Z)‐3‐hexenyl acetate did not increase moth catches. The addition of pear ester to the sex pheromone lure marginally increased moth catches. The use of TA and AA together significantly increased moth catches compared with the use of only one of the two components. Traps with the TA/AA lure outperformed the Ajar trap baited with a liquid TA plus sugar bait. The emission rate of AA was not a significant factor affecting the performance of the TA/AA lure. The addition of TA/AA significantly increased moth catches when combined with the 2‐PH lure. The TA/AA lure also allowed traps to catch both sexes. Catch of C. pomonella with the 2‐PH lure was comparable to the use of codlemone; however, moth catch was significantly reduced with the 2‐PH/PE lure. Optimization of these complex lures can likely further improve managers’ ability to monitor G. molesta and help to develop multispecies tortricid lures for use in individual traps.     

Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts.

The requirements for transformation of rat embryo fibroblasts (REFs) by transfected ras and myc oncogenes were explored. Under conditions of dense monolayer culture, neither oncogene was able to transform REFs on its own. However, the introduction of a ras oncogene together with a selectable neomycin resistance marker into REFs allowed killing of the normal nontransfected cells and the outgrowth of colonies of ras transformants, 10% of which survived crisis and became tumorigenic. These cells expressed greater than 10-fold-higher levels of ras p21 than tumorigenic cells cotransfected with ras and myc oncogenes. The myc oncogene similarly was unable to induce tumorigenic conversion of REFs unless especially refractile colonies of oncogene-bearing cells, produced by use of a cotransfected selectable marker, were picked and subcultured. Tumorigenic conversion of REFs by single transfected oncogenes appears to require special culture conditions and high levels of gene expression.     

People Efficiently Explore the Solution Space of the Computationally Intractable Traveling Salesman Problem to Find Near-Optimal Tours

Humans need to solve computationally intractable problems such as visual search, categorization, and simultaneous learning and acting, yet an increasing body of evidence suggests that their solutions to instantiations of these problems are near optimal. Computational complexity advances an explanation to this apparent paradox: (1) only a small portion of instances of such problems are actually hard, and (2) successful heuristics exploit structural properties of the typical instance to selectively improve parts that are likely to be sub-optimal. We hypothesize that these two ideas largely account for the good performance of humans on computationally hard problems. We tested part of this hypothesis by studying the solutions of 28 participants to 28 instances of the Euclidean Traveling Salesman Problem (TSP). Participants were provided feedback on the cost of their solutions and were allowed unlimited solution attempts (trials). We found a significant improvement between the first and last trials and that solutions are significantly different from random tours that follow the convex hull and do not have self-crossings. More importantly, we found that participants modified their current better solutions in such a way that edges belonging to the optimal solution (“good” edges) were significantly more likely to stay than other edges (“bad” edges), a hallmark of structural exploitation. We found, however, that more trials harmed the participants'' ability to tell good from bad edges, suggesting that after too many trials the participants “ran out of ideas.” In sum, we provide the first demonstration of significant performance improvement on the TSP under repetition and feedback and evidence that human problem-solving may exploit the structure of hard problems paralleling behavior of state-of-the-art heuristics.     

Monitoring oriental fruit moth and codling moth (Lepidoptera: Tortricidae) with combinations of pheromones and kairomones

Experiments were conducted in North and South America during 2012–2013 to evaluate the use of lure combinations of sex pheromones (PH), host plant volatiles (HPVs) and food baits in traps to capture the oriental fruit moth, Grapholita molesta (Busck), and codling moth, Cydia pomonella (L.), in pome and stone fruit orchards treated with sex pheromones. The combination of the sex pheromone of both species (PH combo lure) significantly increased G. molesta and marginally decreased C. pomonella captures as compared with captures of each species with either of their sex pheromones alone. The addition of a HPV combination lure [(E,Z)‐2,4‐ethyl decadienoate plus (E)‐β‐ocimene] or acetic acid used alone or together did not significantly increase the catch of either species in traps with the PH combo lure. The Ajar trap baited with terpinyl acetate and brown sugar (TAS bait) caught significantly more G. molesta than the delta trap baited with PH combo plus acetic acid in California during 2012. The addition of a PH combo lure to an Ajar trap significantly increased catches of G. molesta compared to the use of the TAS bait or PH combo lure alone in 2013. Female G. molesta were caught in TAS‐baited Ajar traps at similar levels with or without the use of additional lures. Ajar traps baited with the TAS bait alone or with (E)‐β‐ocimene and/or PH combo lures caught significantly fewer C. pomonella than delta traps with sex pheromone alone. Ajar traps with 6.4‐mm screened flaps caught similar numbers of total and female G. molesta as similarly baited open Ajar traps, and with a significant reduction in the catch of non‐targets. Broader testing of HPV and PH combo lures for G. molesta in either delta or screened or open Ajar traps is warranted.     

Chromosome positioning in the interphase nucleus

Chromosomes occupy distinct territories in the interphase cell nucleus. These chromosome territories are non-randomly arranged within the nuclear space. We are only just uncovering how chromosome territories are organized, what determines their position and how their spatial organization affects the expression of genes and genomes. Here, we discuss emerging models of non-random nuclear chromosome organization and consider the functional implications of chromosome positioning for gene expression and genome stability.     

Gene expression profiling of hereditary exencephaly in chickens

In this preliminary study, differentially expressed genes were investigated in cranial tissues from chickens with hereditary exencephaly using cDNA microarrays containing 1,152 genes and expressed sequence tags (ESTs). Genes showing twofold or greater differences at P < 0.05 between affected and normal cranial cells were considered to be candidates for hereditary exencephaly in chicken. Eighteen ESTs (11 known genes/homologues) were upregulated and 108 ESTs (51 known genes/homologues) were downregulated. The EST AL584231 (ROS006C9), orthologous to human MTHFD1, a known candidate gene for human neural tube defects (NTDs), was expressed at the same level both in normal and affected chicken cranial tissues. ESTs AL584253 (ROS006F7, thioredoxin reductase 1) and AL585511 (ROS024H9, thioredoxin), both involved in NTD pathogenic pathways in mice, were downregulated and had mean ratios of 0.41 and 0.04 for expression in affected vs. normal cells respectively. Expression differences of these two ESTs were confirmed by quantitative real-time polymerase chain reaction. These data indicate that ESTs AL584253 and AL585511 are candidates for hereditary exencephaly in chickens.