Neural correlates of individual differences in strategic retrieval processing.

Processes engaged when information is encoded into memory are an important determinant of whether that information will be recovered subsequently. Also influential, however, are processes engaged at the time of retrieval, and these were investigated here by using event-related potentials (ERPs) to measure a specific class of retrieval operations. These operations were revealed by contrasts between ERPs elicited by new (unstudied) test items in distinct tasks, the assumption being that these contrasts index operations that are engaged in service of retrieval and that vary according to the demands of different retrieval tasks. Specific functional accounts of this class of retrieval processing operations assume that they influence the accuracy of memory judgments, and this experiment was designed to test for the first time whether this is in fact the case. Toward this end, participants completed 2 retrieval tasks while ERPs were acquired, and the extent to which processes were engaged differentially across tasks in service of retrieval was operationalized as the magnitude of the differences between the new-item ERPs that were elicited. This measure correlated positively with response accuracy on the tasks, which provides strong evidence that this class of retrieval processing operations benefits the accuracy of memory judgments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The impact of childhood symptoms of conduct disorder on driver aggression in adulthood

Background

Despite limited empirical investigation, existing scientific literature suggests that individuals with a history or current diagnosis of conduct disorder (CD) may be more likely to demonstrate reckless and aggressive driving. Much of the limited research in this field examines the impact of childhood CD on driver behaviour and collision risk in young adults. Few if any, studies assess the impact of this disorder on driver behaviour beyond age 21 years. The current research is a population-based study of the impact of CD symptoms during childhood on the risk of engaging in driver aggression during adulthood.

Methods

Data are based on telephone interviews with 5230 respondents who reported having driven in the past year. Data are derived from the 2011–2013 cycles of the CAMH Monitor, an ongoing cross-sectional survey of adults in Ontario, Canada aged 18 years and older. A binary logistic regression analysis of self-reported driver aggression in the previous 12 months was conducted, consisting of measures of demographic characteristics, driving exposure, problem substance use, alcohol- and drug-impaired driving, symptoms of attention deficit hyperactivity disorder, and childhood (before age 15) symptoms of CD.

Results

When entered with demographic characteristics, driving exposure, and other potential confounders, childhood symptoms of CD increased the odds of reporting driver aggression more than two-fold (adjusted OR = 2.12). Exploratory analyses of the interaction between childhood symptoms of CD and age was not a significant predictor of driver aggression.

Conclusions

Results suggest that symptoms of CD during childhood are associated with significantly increased odds of self-reported driver aggression during adulthood. Limitations and future directions of the research are discussed.     

Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues

Pactamycin is a bacteria‐derived aminocyclitol antibiotic with a wide‐range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites.     

Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring

Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.     

Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.     

SARM1 Ablation Is Protective and Preserves Spatial Vision in an In Vivo Mouse Model of Retinal Ganglion Cell Degeneration

The challenge of developing gene therapies for genetic forms of blindness is heightened by the heterogeneity of these conditions. However, mechanistic commonalities indicate key pathways that may be targeted in a gene-independent approach. Mitochondrial dysfunction and axon degeneration are common features of many neurodegenerative conditions including retinal degenerations. Here we explore the neuroprotective effect afforded by the absence of sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1), a prodegenerative NADase, in a rotenone-induced mouse model of retinal ganglion cell loss and visual dysfunction. Sarm1 knockout mice retain visual function after rotenone insult, displaying preservation of photopic negative response following rotenone treatment in addition to significantly higher optokinetic response measurements than wild type mice following rotenone. Protection of spatial vision is sustained over time in both sexes and is accompanied by increased RGC survival and additionally preservation of axonal density in optic nerves of Sarm1^−/− mice insulted with rotenone. Primary fibroblasts extracted from Sarm1^−/− mice demonstrate an increased oxygen consumption rate relative to those from wild type mice, with significantly higher basal, maximal and spare respiratory capacity. Collectively, our data indicate that Sarm1 ablation increases mitochondrial bioenergetics and confers histological and functional protection in vivo in the mouse retina against mitochondrial dysfunction, a hallmark of many neurodegenerative conditions including a variety of ocular disorders.     

Subtle variations in the structure of crosslinked epoxy networks and the impact upon mechanical and thermal properties

Presented here is an investigation of the structure–property relationships of crosslinked networks using three bi-functional glycidyl ether aromatic epoxy resins, two bi-aryl and one tri-aryl, cured with bi- and tri-aryl amines. Subtle changes to the monomer chemistry including changing aromatic substitution patterns from meta to para, methylene to isopropyl and isopropyl to ether were explored. Changing an epoxy resin backbone from methylene to isopropyl enhances backbone rigidity thus increasing glass transition temperature (T_g), yield strength, and strain despite reducing modulus. Changing meta-substitution to para increases T_g and yield strain while leaving strength unaffected and reducing modulus. Changing isopropyl linkages to ether reduces modulus, strength, T_g, and yield strain reflecting increased molecular flexibility. Using three instead of two aromatic rings increases the molecular weight between crosslinks thereby decreasing T_g and yield strain while increasing modulus and strength. Despite the complexities of multiple systems for varying epoxy resins and amine hardeners, the effect upon network properties is explained in terms of short- and long-range molecular and segmental mobility, crosslink density, and equilibrium packing density. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48874.     

Role of speciation in organotin toxicity to the yeast Candida maltosa

Assessment of organometal pollution requires an understanding of the various processes that influence the bioavailability and toxicity of the contaminant. Organotins may exist as both cationic species and neutral hydroxides in aqueous solution, with the formation of chloride species in the presence of Cl-. Although these species have different chemical properties, there is very little information on the influence of speciation on organotin and microbial cell interactions. Tributyltin (TBT) and triphenyltin (TPT) interactions with the yeast Candida maltosa were investigated between pH 3.5 and 7.5 and in up to 0.5 M NaCl at pH 5.5. Toxicity increased with both pH and NaCl concentration and the mechanisms of interaction depended on the species present in solution. TBT and TPT interacted by different mechanisms, as evidenced by action on membrane fluidity. Furthermore, there was a strong correlation between toxicity and overall octanol-water distribution ratio (D(OW)) of organotin compounds. Triorganotin cations are less toxic than triorganotin hydroxides, which are in turn less toxic than triorganotin chlorides. These findings underline the importance of speciation effects on organotin interactions in the environment.