Biology subjects

Shinkle, J.

Publications and source records attributed to Shinkle, J..

4 recordsLinked to original sources

bioRxiv2023

The ventral hippocampus and nucleus accumbens as neural substrates for cocaine contextual memory reconsolidation

Drug craving triggered by cues that were once associated with drug intoxication is a major contributor to continued drug-seeking behaviors. Addictive drugs engage molecular pathways of associative learning and memory. Reactivated memories are vulnerable to disruption by interference with the process of reconsolidation, hence targeting reconsolidation could be a strategy to reduce cue-induced drug craving and relapse. Here we examined the circuitry of cocaine contextual memory reconsolidation and explored neuroplasticity following memory reactivation. Mice underwent chemogenetic inhibition of either nucleus accumbens (NA) neurons or the glutamatergic projection neurons from the ventral hippocampus (vHPC) to NA using inhibitory designer receptors exclusively activated by designer drugs (iDREADD). Mice underwent cocaine conditioned place preference followed by reactivation of the cocaine contextual memory. Clozapine-N-oxide (CNO) was administered after memory reactivation to inhibit either NA neurons or the accumbens-projecting vHPC neurons during the reconsolidation period. When retested 3 days later, a significant reduction in the previously established preference for the cocaine context was found in both conditions. FosTRAP2-Ai14 mice were used to identify neurons activated by cocaine memory recall and to evaluate plasticity in NA medium spiny neurons (MSNs) and vHPC pyramidal neurons upon recall of cocaine memories. Results indicate a significant increase in dendritic spine density in NA MSNs activated by cocaine memory recall, particularly of the thin spine type. Sholl analysis indicated longer dendritic length and more branching of NA MSNs after cocaine memory recall than without memory reactivation. vHPC neurons showed increased spine density, with the most robust change in stubby spines. These results implicate a circuit involving glutamatergic projections from the vHPC onto NA neurons which is necessary for the reconsolidation of cocaine memories. Interruption of cocaine memory reconsolidation reduced drug-seeking behavior.

neuroscience↗

bioRxiv2022

Natural Shortwave UV-B Radiation Increases UV absorbing pigments levels in Texas native grasses Chasmanthium latifolium and Bouteloua curtipendula

Plants are routinely exposed to UV-B radiation (280-315 nm) as a natural component of incident solar radiation. UV-B radiation is relevant to plants as both a source of damage and as a photomorphogenic cue, but the relative impacts of different wavelengths within the UV-B waveband are largely unresolved. Previous studies indicate that the full spectrum of solar UV-B radiation elicits unique responses in model plants under laboratory conditions compared to photons within the longwave UV-B band (300-315 nm), but the impacts of shortwave UV-B radiation (SW-UVB; 280-300 nm) remain unknown in a field environment. In this study, we examine the impact of shortwave UV-B radiation on the pigmentation and morphology of C3 shade-adapted inland sea oats (Chasmanthium latifolium) and C4 sun-adapted side-oats grama (Bouteloua curtipendula) in field conditions. We characterized the responses of these grasses to SW-UVB radiation by placing UV-naive individuals under SW-UVB excluding or transmitting filters at three field sites in Central Texas and measuring their responses through leaf pigment extract absorbance, leaf surface reflectance, and whole leaf chlorophyll and flavonoid content. We found that both species exhibited changes to their UV-B associated traits following exposure to the field environment, which were influenced by field site location, maximum daily temperature, and SW-UVB exposure. In particular, C. latifolium increased the ratio of its maximum to minimum absorbance in response to SW-UVB, while B. curtipendula exhibited higher flavonoid content in response to SW-UVB exposure. We believe this is the first time that the effects of SW-UVB radiation have been documented in a field environment.

plant biology↗

bioRxiv2019

Determinants of telomere length across human tissues

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in non-blood, disease-relevant tissue types. Here we characterize variability in TL measurements for 6,391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) Project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation impacts TL in multiple tissue types, and that TL can mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.\n\nONE SENTENCE SUMMARYTelomere length varies by tissue type but is generally correlated among tissue types (positively) and with age (negatively).

genetics↗

bioRxiv2018

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., \"direct\" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5,069 Bangladeshi adults with substantial relatedness. For each of the 7,254 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL (({Delta}LTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness ({phi}). The association between Tshared and ({Delta}LTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs ({phi} >0.05), the association between Tshared and ({Delta}LTL)2 (P=0.002) was stronger than the association between {phi} and ({Delta}LTL)2 (P=0.45). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere \"reprogramming\" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direction transmission.

genetics↗