Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.     

Continuously extruded micro‐textured polypropylene films

The continuous extrusion of micro‐textured isotactic polypropylene (i‐PP) film and its tribological properties are reported. As analyzed by scanning electron microscopy, a rectangular‐semicircular micro‐patterned die successfully produced extruded cast‐films with hill‐like micro‐texture. Such films displayed static and kinetic coefficients of friction (COF_s and COF_k) values of 0.247 ± 0.028 and 0.245 ± 0.003, respectively, for a steel fixture sliding along the micro‐texture of the film. The equivalent COF_s and COF_k values for non‐textured (NT) films were 0.369 ± 0.036 and 0.340 ± 0.024, respectively, confirming that textured films displayed a reduction in COF of about 30%. For textured and NT films sliding on textured films, the COF_k values were even lower at 0.161 ± 0.013 and 0.113 ± 0.004, which represents about 20–40% reduction as compared with that for the NT‐NT counterparts. Films coated with a silicone lubricant displayed COF_s and COF_k values of 0.334 ± 0.042 and 0.099 ± 0.012, respectively, for NT films sliding over lubricated NT films, and 0.426 ± 0.031 and 0.063 ± 0.006, respectively, for textured films sliding over lubricated textured films. The COF_k values for textured/non‐lubricated films approach those of NT/lubricated films, indicating that micro‐textured polypropylene films may be used in environmentally sensitive applications where lubricants and fluorinated additives may not be used for reducing friction. POLYM. ENG. SCI., 54:2147–2154, 2014. © 2013 Society of Plastics Engineers     

Repurposing the Pummerer Rearrangement: Determination of Methionine Sulfoxides in Peptides

The reversible oxidation of methionine residues in proteins has emerged as a biologically important post-translational modification. However, detection and quantitation of methionine sulfoxide in proteins is difficult. Our aim is to develop a method for specifically derivatizing methionine sulfoxide residues. We report a Pummerer rearrangement of methionine sulfoxide treated sequentially with trimethylsilyl chloride and then 2-mercaptoimidazole or pyridine-2-thiol to produce a dithioacetal product. This derivative is stable to standard mass spectrometry conditions, and its formation identified oxidized methionine residues. The scope and requirements of dithioacetal formation are reported for methionine sulfoxide and model substrates. The reaction intermediates have been investigated by computational techniques and by ¹³C NMR spectroscopy. These provide evidence for an α-chlorinated intermediate. The derivatization allows for detection and quantitation of methionine sulfoxide in proteins by mass spectrometry and potentially by immunochemical methods.     

Gene Discovery in Gelsemium Highlights Conserved Gene Clusters in Monoterpene Indole Alkaloid Biosynthesis

Genome mining is a routine technique in microbes for discovering biosynthetic pathways. In plants, however, genomic information is not commonly used to identify novel biosynthesis genes. Here, we present the genome of the medicinal plant and oxindole monoterpene indole alkaloid (MIA) producer Gelsemium sempervirens (Gelsemiaceae). A gene cluster from Catharanthus roseus, which is utilized at least six enzymatic steps downstream from the last common intermediate shared between the two plant alkaloid types, is found in G. sempervirens, although the corresponding enzymes act on entirely different substrates. This study provides insights into the common genomic context of MIA pathways and is an important milestone in the further elucidation of the Gelsemium oxindole alkaloid pathway.     

Chemical Ecology and Sociality in Aphids: Opportunities and Directions

Aphids have long been recognized as good phytochemists. They are small sap-feeding plant herbivores with complex life cycles that can involve cyclical parthenogenesis and seasonal host plant alternation, and most are plant specialists. Aphids have distinctive traits for identifying and exploiting their host plants, including the expression of polyphenisms, a form of discrete phenotypic plasticity characteristic of insects, but taken to extreme in aphids. In a relatively small number of species, a social polyphenism occurs, involving sub-adult “soldiers” that are behaviorally or morphologically specialized to defend their nestmates from predators. Soldiers are sterile in many species, constituting a form of eusociality and reproductive division of labor that bears striking resemblances with other social insects. Despite a wealth of knowledge about the chemical ecology of non-social aphids and their phytophagous lifestyles, the molecular and chemoecological mechanisms involved in social polyphenisms in aphids are poorly understood. We provide a brief primer on aspects of aphid life cycles and chemical ecology for the non-specialists, and an overview of the social biology of aphids, with special attention to chemoecological perspectives. We discuss some of our own efforts to characterize how host plant chemistry may shape social traits in aphids. As good phytochemists, social aphids provide a bridge between the study of insect social evolution sociality, and the chemical ecology of plant-insect interactions. Aphids provide many promising opportunities for the study of sociality in insects, and to understand both the convergent and novel traits that characterize complex sociality on plants.     

Mealtime Behaviors and Food Consumption of Perceived Picky and Nonpicky Eaters through Home Use Test

Picky eating has been investigated through numerous surveys and food recalls, but few studies have applied in‐home meal evaluations as a method to investigate behaviors and food preferences of children perceived by their parent to be a picky eater (PE) or nonpicky eater (NPE). A 2‐wk in‐home meal study was completed to investigate differences in PE and NPE mealtime behaviors and food selections using real‐time parental observations. Parents (n = 170) and their 2‐ to 4‐y‐old children (83 PE and 87 NPE) evaluated 5 standardized meals in‐home. Parents recorded their child's and their own hedonic liking of the products and completed an assessment of their child's behavior and consumption at each meal. Significant differences were found between perceived PE and NPE children for all 16 behaviors assessed. On average, perceived NPE were assessed to consume a higher percentage of the meal served and to have higher acceptance scores for most of the foods evaluated. Some foods, though, like breaded chicken and plain pasta, were liked equally by PE and NPE. Several significant differences in hedonic liking were revealed when PE children were compared to their parents. Yet, few differences in liking occurred between NPE children and their parents or between the 2 parental groups. Because study participants evaluated meals real‐time rather than memory recall, the differences and similarities found between perceived PE and NPE may be considered direct experiential evidence with reduced subjective bias as created when subjects recall past experiences. Thus, findings from this study can provide the foundation to establish an objective definition and classification of PE and NPE.