Analysis of Galvanic Skin Response: Potential Relationships to Stimulus Responsivity and Brain Dopamine Signal

Fibromyalgia is a chronic pain disorder that presents itself with no apparent medical explanation for the pain. Functional alterations of neurotransmitters such as dopamine (DA) have been implicated in fibromyalgia neuropathology. It is not known how central dopamine function in pain is associated with objective peripheral measurements that are thought to be associated with the presence of pain and stress. Galvanic skin response (GSR), is a physiological measure of nervous system activation. GSR could potentially give insight to novel aspects of DA function. In this study, GSR was recorded from fibromyalgia patients (FM) and healthy controls (HC) while they underwent scanning with [18F]-fallypride (FAL) Positron Emission Tomography (PET). FAL is a D2/D3 DA receptor antagonist that is sensitive to changes in DA levels in the brain. Given the involvement of DA in cognitive processes, FAL PET can be used to examine baseline DA activity as well as changes from baseline during cognitive load tasks. Relationships between GSR and working memory load, acute pain, and DA function were studied and compared between FM and HC

CRISPR/Cas9-mediated mutagenesis of CAROTENOID CLEAVAGE DIOXYGENASE 8 in tomato provides resistance against the parasitic weed Phelipanche aegyptiaca.

Broomrapes (Phelipanche aegyptiaca and Orobanche spp.) are obligate plant parasites that cause extreme damage to crop plants. The parasite seeds have strict requirements for germination, involving preconditioning and exposure to specific chemicals strigolactones [SLs] exuded by the host roots. SLs are plant hormones derived from plant carotenoids via a pathway involving the Carotenoid Cleavage Dioxygenase 8 (CCD8). Having no effective means to control parasitic weeds in most crops, and with CRISPR/Cas9 being an effective gene-editing tool, here we demonstrate that CRISPR/Cas9-mediated mutagenesis of the CCD8 gene can be used to develop host resistance to the parasitic weed P. aegyptiaca. Cas9/single guide (sg) RNA constructs were targeted to the second exon of CCD8 in tomato (Solanum lycopersicum L.) plants. Several CCD8Cas9 mutated tomato lines with variable insertions or deletions in CCD8 were obtained with no identified off-targets. Genotype analysis of T1 plants showed that the introduced CCD8 mutations are inherited. Compared to control tomato plants, the CCD8Cas9 mutant had morphological changes that included dwarfing, excessive shoot branching and adventitious root formation. In addition, SL-deficient CCD8Cas9 mutants showed a significant reduction in parasite infestation compared to non-mutated tomato plants. In the CCD8Cas9 mutated lines, orobanchol (SL) content was significantly reduced but total carotenoids level and expression of genes related to carotenoid biosynthesis were increased, as compared to control plants. Taking into account, the impact of plant parasitic weeds on agriculture and difficulty to constitute efficient control methods, the current study offers insights into the development of a new, efficient method that could be combined with various collections of resistant tomato rootstocks

Correlation Between Chromatid Deletion Production and Progression of the DNA Replication Fork in UV-Irradiated S Phase Xenopus Cells

Experimentation was performed primarily to determine whether progression of the DNA replication fork along segments of S phase Xenopus chromosomes, which contain UV-induced pre-aberrational lesions, plays a significant role in conversion of these lesions into chromatid deletions. Specifically, a Xenopus chromosome that was both easy to identify and that possessed a single DNA replication fork in one arm was found and used to conduct the experimentation. This chromosome was exposed to UV in early S phase and a Bromodeoxyuridine/Giemsa differential staining technique was applied in conjunction with conventional aberrational techniques to correlate progression of the DNA replication fork through segments of this arm with chromatid deletion production in these segments. The results point to direct evidence for the role of the DNA replication fork in converting some UV-induced pre-aberrational DNA damage into chromosomal deletions

Symposium Review: \u3cem\u3eAmish and Old Order Mennonite Schools: A Concise History\u3c/em\u3e—Joseph Stoll; and The School by the Cornfield—Samuel Coon

Joseph Stoll, in Amish and Old Order Mennonite Schools: A Concise History, and Samuel Coon, in The School by the Cornfield, provide two very different perspectives on the struggle to establish Anabaptist schools. The books contrast primarily in their geographic and chronological scope. However, both write about parochial schools with a voice sympathetic to the vision of Amish and Mennonite school founders. They use similar sources, drawing on newspaper accounts, published Amish schools’ histories, and Amish and Mennonite periodicals, as well as personal recollections from individuals involved in school conflicts. [First paragraph.

Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers

RATIONALE: Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood. OBJECTIVES: To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD). METHODS: NTS subjects (n = 10) and SD (n = 13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND. RESULTS: Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST. CONCLUSIONS: Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures

Reliability of Striatal [11C]Raclopride Binding in Smokers Wearing Transdermal Nicotine Patches

PURPOSE: In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches. METHODS: Eleven male smokers were scanned twice with RAC on separate days while wearing TNP. RESULTS: Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 (p < 0.0001). CONCLUSION: Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine

What happens if you single out? An experiment

We present an experiment investigating the effects of singling out an individual on trust and trustworthiness. We find that (a) trustworthiness falls if there is a singled out subject; (b) non-singled out subjects discriminate against the singled out subject when they are not responsible of the distinct status of this person; (c) under a negative frame, the singled out subject returns significantly less; (d) under a positive frame, the singled out subject behaves bimodally, either selecting very low or very high return rates. Overall, singling out induces a negligible effect on trust but is potentially disruptive for trustworthiness

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin