Biology subjects

Johnson, J. D.

Publications and source records attributed to Johnson, J. D..

42 records · Page 3Linked to original sources

bioRxiv2019

Repetition Attenuates the Influence of Recency on Recognition Memory: Behavioral and Electrophysiological Evidence

Studies of recognition memory often demonstrate a recency effect on behavioral performance, whereby response times (RTs) are faster for stimuli that were previously presented recently as opposed to more remotely in the past. This relationship between performance and presentation lag has been taken to reflect that memories are accessed by serially searching backwards in time, such that RT indicates the self-terminating moment of such a process. Here, we investigated the conditions under which this serial search gives way to more efficient means of retrieving memories. Event-related potentials (ERPs) were recorded during a continuous recognition task in which subjects made binary old/new judgments to stimuli that were each presented up to four times across a range of lags. Stimulus repetition and shorter presentation lag both gave rise to speeded RTs, consistent with previous findings, and we novelly extend these effects to a robust latency measure of the left parietal ERP effect associated with retrieval success. Importantly, the relationship between repetition and recency was further elucidated, such that repetition attenuated lag-related differences that were initially present in both the behavioral and neural latency data. These findings are consistent with the idea that a serial search through recent memory can quickly be abandoned in favor of relying on more efficient time-independent cognitive processes or neural signals.

neuroscience↗

bioRxiv2019

Plumage redness signals mitochondrial function in the House Finch

Carotenoid coloration is widely recognized as a signal of individual condition in various animals, but despite decades of study, the mechanisms that link carotenoid coloration to condition remain unresolved. Most birds with red feathers convert yellow dietary carotenoids to red carotenoids in an oxidation process requiring the gene encoding the putative cytochrome P450 enzyme CYP2J19. Here, we tested the hypothesis that the process of carotenoid oxidation and feather pigmentation is functionally linked to mitochondrial performance. Consistent with this hypothesis, we observed high levels of red ketolated carotenoids associated with the hepatic mitochondria of molting wild house finches (Haemorhous mexicanus), and upon fractionation, we found the highest concentration of ketolated carotenoids in the inner mitochondrial membrane. We further found that the redness of growing feathers was positively related to the performance of liver mitochondria. Structural modeling of CYP2J19 supports a direct role of this protein in carotenoid ketolation that may be functionally linked to cellular respiration. These observations suggest that feather coloration serves as a signal of core functionality through inexorable links to cellular respiration in the mitochondria.

evolutionary biology↗

bioRxiv2019

Presynaptic boutons that contain mitochondria are more stable

Addition and removal of presynaptic terminals reconfigures neuronal circuits of the mammalian neocortex, but little is known about how this presynaptic structural plasticity is controlled. Since mitochondria can regulate presynaptic function, we investigated whether the presence of axonal mitochondria relates to structural plasticity of presynaptic boutons in mouse neocortex. We found that the overall density of axonal mitochondria did not appear to influence loss and gain of boutons. However, positioning of mitochondria at individual presynaptic sites did relate to increased stability of those boutons. In line with this, synaptic localisation of mitochondria increased as boutons aged and showed differing patterns of localisation at en passant and terminaux boutons. These results suggest that mitochondria accumulate locally at boutons over time to increase bouton stability.

neuroscience↗

bioRxiv2019

Modulation of Insr and insulin receptor signaling by hyperinsulinemia in vitro and in vivo

Hyperinsulinemia is commonly viewed as a compensatory response to insulin resistance, yet studies have suggested that chronically elevated insulin may also drive insulin resistance. The molecular mechanisms underpinning this potentially cyclic process remain poorly defined, especially on a transcriptome-wide level. To study the direct effects of prolonged exposure to excess insulin in muscle cells, we incubated C2C12 myotubes with elevated insulin for 16 hours, followed by 6 hours of serum starvation, and established that acute AKT and ERK signaling were attenuated in this model of in vitro hyperinsulinemia. Global RNA-sequencing of cells both before and after nutrient withdrawal highlighted genes in the insulin signaling, FOXO signaling, and glucose metabolism pathways indicative of hyperinsulinemia and starvation programs. We observed that hyperinsulinemia led to a substantial reduction in insulin receptor (Insr) gene expression, and subsequently a reduced surface INSR and total INSR protein, both in vitro and in vivo. Transcriptomic meta-analysis in >450 human samples demonstrated that fasting insulin reliably and negatively correlated with insulin receptor (INSR) mRNA in skeletal muscle. Bioinformatic modeling combined with RNAi, identified SIN3A as a negative regulator of Insr mRNA (and JUND, MAX, and MXI as positive regulators of Irs2 mRNA). Together, our analysis identifies novel mechanisms which may explain the cyclic processes underlying hyperinsulinemia-induced insulin resistance in muscle, a process directly relevant to the etiology and disease progression of type 2 diabetes.

physiology↗

bioRxiv2019

Endogenous insulin contributes to pancreatic cancer development

Obesity and early-stage type 2 diabetes (T2D) increase the risk for many cancers, including pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking obesity and T2D to cancer have not been established, preventing targeted interventions. Arguments have been made that hyperinsulinemia, hyperglycemia, or inflammation could drive cancer initiation and/or progression1. Hyperinsulinemia is a cardinal feature of obesity and T2D, and is independently associated with PDAC incidence and mortality2-4, even in non-obese people5. Despite ample human epidemiological evidence linking hyperinsulinemia to PDAC, there is no direct in vivo evidence of a causal role for endogenous insulin in cancer in any system. Using mice with reduced insulin gene dosage6, 7, we show here that a modest reduction in endogenous insulin production leads to a ~50% reduction in pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in high fat diet-fed mice expressing the KrasG12D oncogene8. The significant reduction in PanIN lesions occurred in the absence of changes in fasting glucose. Reduced insulin also led to a ~50% reduction in pancreatic fibrosis, suggesting that endogenous insulin drives PanIN development, in part, via its pro-fibrotic effects on the stroma surrounding acinar cells and PanIN. Collectively, our data indicate that endogenous insulin hypersecretion contributes causally to pancreatic cancer development. This suggests a modest reduction in fasting insulin via lifestyle interventions or therapeutics may be useful in cancer prevention.

cancer biology↗

bioRxiv2017

Failure to reactivate salient episodic information during indirect and direct tests of memory retrieval

Several fMRI and EEG studies have demonstrated that successful episodic retrieval is accompanied by the reactivation of cortical regions that were active during encoding. These findings are consistent with influential models of episodic memory that posit that conscious retrieval (recollection) relies on hippocampally-mediated cortical reinstatement. Evidence of reactivation corresponding to episodic information that is beyond conscious awareness at the time of memory retrieval, however, is limited. A recent exception is from an EEG study by Wimber, Maa{beta}, Staudigl, Richardson-Klavehn, and Hanslmayr (2012) in which words were encoded in the context of highly salient visual flicker entrainment and then presented at retrieval in the absence of any flicker. In that study, coherent (phase-locked) neural activity was observed at the corresponding entrained frequencies during retrieval, consistent with the notion that encoding representations were reactivated. Given the important implications of unconscious reactivation to past findings and the modeling literature, the current study set out to provide a direct replication of the previous study. Additionally, an attempt was made to extend such findings to intentional retrieval by acquiring EEG while subjects were explicitly asked to make memory judgments about the flicker frequency from encoding. Throughout a comprehensive set of analyses, the current study consistently failed to demonstrate evidence for unconscious reactivation, and instead provided support that test items were indistinguishable according to their prior encoding context. The findings thus establish an important boundary condition for the involvement of cortical reinstatement in episodic memory.

neuroscience↗