Impacts of Drugs on Neurotransmission

The most sophisticated and mysterious human organ is the brain. The human brain is made up of billions of neurons, which are working nonstop to send and receive messages to regulate the body’s basic functions. Neurons communicate by releasing neurotransmitters from a sending neuron into the synapse, then a receiving neuron picks up the signals on its receptors from neurotransmitters. Drugs can interfere with the communication between neurons in the brain. They can affect the way people feel, react or behave. Drug use impacts the brain’s neuronal circuits which may lead to inflexible behaviors, lack of self-control, and compulsive drug use. Unlike most diseases causing cellular dysfunction, addiction is unusual. It is a disorder caused by addictive drugs acting to reinforce their acquisition. Addictive drugs which have different structures perform in large varieties of actions, however, they all can dissociate striatal dopamine neurotransmission from its ordinary drive; enhancing the neurotransmitters by environmental cues. Drugs can alter neurotransmission in three major ways: (1) Stimulate neurons, mimicking natural neurotransmitters (i.e., nicotine attaches acetylcholine receptors); (2) alter neurotransmission through interaction with molecular components of neurotransmission (i.e., cocaine attaches to the dopamine transporter); (3) increasing or decreasing number of receptors stimulated in neurotransmission (i.e., benzodiazepines enhance effects of GABA;). Drug addiction can affect important areas of the brain which control basic functions. The basal ganglia, the extended amygdala, the prefrontal cortex, and the brain stem are the main areas disrupted by addictive drugs. To address the negative impact of addictive drugs on the brain, an interactive project affiliated with Dr. Caroline Easton’s multidisciplinary Behavioral Health Medical Interactive Therapy (BHMT) team was created to promote a healthy lifestyle

ACRYLONITRILE HAS DISTINCT HORMETIC EFFECTS ON ACETYLCHOLINESTERASE ACTIVITY IN MOUSE BRAIN AND BLOOD THAT ARE MODULATED BY ETHANOL

Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on acetylcholinesterase (AChE) activity remain controversial. This study aimed to determine the dose-response effects of AN on AChE activity and the modulatory role of ethanol pretreatment. A total of 144 Kunming mice were randomly divided into 18 groups: nine groups received 5% ethanol in their drinking water, and the remaining nine groups received regular tap water. One week later, both the ethanol and tap water only groups were given an intraperitoneal injection of AN at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20 mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h later. Blood AChE activity was higher in AN-injected mice than in controls at all doses. AChE activity in blood increased in a dose-dependent manner, peaking at 0.156 mg/kg, after which a gradual decrease ensued, displaying a β-typed dose-response relationship. In contrast, brain AChE activity, following a single AN injection, was consistently lower than in control mice, and continued to fall up to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses. Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity indistinguishable from that of control mice, demonstrating a typical U-typed dose-response relationship. The activity of AChE in the blood and brain of the AN + ethanol-treated groups displayed a shift to the right, and the magnitude of the decrease in AChE activity induced by AN was attenuated relative to the AN-only group. These results suggest that AN affects AChE activity in both mouse blood and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of AN on AChE, indicating that parent AN has a more prominent role than its metabolites in modulating enzyme activity

Author Correction: The disease resistance protein SNC1 represses the biogenesis of microRNAs and phased siRNAs.

The original version of this Article contained an error in the spelling of the author Beixin Mo, which was incorrectly given as Beixing Mo. This has now been corrected in both the PDF and HTML versions of the Article

Ndrg2 regulates vertebral specification in differentiating somites

AbstractIt is generally thought that vertebral patterning and identity are globally determined prior to somite formation. Relatively little is known about the regulators of vertebral specification after somite segmentation. Here, we demonstrated that Ndrg2, a tumor suppressor gene, was dynamically expressed in the presomitic mesoderm (PSM) and at early stage of differentiating somites. Loss of Ndrg2 in mice resulted in vertebral homeotic transformations in thoracic/lumbar and lumbar/sacral transitional regions in a dose-dependent manner. Interestingly, the inactivation of Ndrg2 in osteoblasts or chondrocytes caused defects resembling those observed in Ndrg2−/− mice, with a lower penetrance. In addition, forced overexpression of Ndrg2 in osteoblasts or chondrocytes also conferred vertebral defects, which were distinct from those in Ndrg2−/− mice. These genetic analyses revealed that Ndrg2 modulates vertebral identity in segmented somites rather than in the PSM. At the molecular level, combinatory alterations of the amount of Hoxc8-11 gene transcripts were detected in the differentiating somites of Ndrg2−/− embryos, which may partially account for the vertebral defects in Ndrg2 mutants. Nevertheless, Bmp/Smad signaling activity was elevated in the differentiating somites of Ndrg2−/− embryos. Collectively, our findings unveiled Ndrg2 as a novel regulator of vertebral specification in differentiating somites

Fast colorimetric detection of copper ions using L-Cysteine functionalized gold nanoparticles

This communication reports an efficient visual detection method of Cu2+ by L-cysteine functionalized gold nanoparticles in aqueous solution. Upon exposure to Cu2+, the gold nanoparticle solution changed from red to blue, in response to surface plasmon absorption of dispersed and aggregated nanoparticles. This colorimetric sensor allows a rapid quantitative assay of Cu2+ down to the concentration range of 10&minus;5 M. Recognition of Cu2+ and formation of the aggregates are proposed to occur via a 2 : 1 sandwich complex between L-cysteine and Cu2+. <br /

Genome-Wide Scan for Runs of Homozygosity Identifies Candidate Genes Related to Economically Important Traits in Chinese Merino

In this study, we estimated the number, length, and frequency of runs of homozygosity (ROH) in 635 Chinese Merino and identified genomic regions with high ROH frequency using the OvineSNP50 whole-genome genotyping array. A total of 6039 ROH exceeding 1 Mb were detected in 634 animals. The average number of ROH in each animal was 9.23 and the average length was 5.87 Mb. Most of the ROH were less than 10 Mb, accounting for 88.77% of the total number of detected ROH. In addition, Ovies aries chromosome (OAR) 21 and OAR3 exhibited the highest and lowest coverage of chromosomes by ROH, respectively. OAR1 displayed the highest number of ROH, while the lowest number of ROH was found on OAR24. An inbreeding coefficient of 0.023 was calculated from ROH greater than 1 Mb. Thirteen regions on chromosomes 1, 2, 3, 5, 6, 10, 11, and 16 were found to contain ROH hotspots. Within the genome regions of OAR6 and OAR11, NCAPG/LCORL, FGF11 and TP53 were identified as the candidate genes related to body size, while the genome region of OAR10 harbored RXFP2 gene responsible for the horn trait. These findings indicate the adaptive to directional trait selection in Chinese Merino

FIERY1 promotes microRNA accumulation by suppressing rRNA-derived small interfering RNAs in Arabidopsis.

Plant microRNAs (miRNAs) associate with ARGONAUTE1 (AGO1) to direct post-transcriptional gene silencing and regulate numerous biological processes. Although AGO1 predominantly binds miRNAs in vivo, it also associates with endogenous small interfering RNAs (siRNAs). It is unclear whether the miRNA/siRNA balance affects miRNA activities. Here we report that FIERY1 (FRY1), which is involved in 5'-3' RNA degradation, regulates miRNA abundance and function by suppressing the biogenesis of ribosomal RNA-derived siRNAs (risiRNAs). In mutants of FRY1 and the nuclear 5'-3' exonuclease genes XRN2 and XRN3, we find that a large number of 21-nt risiRNAs are generated through an endogenous siRNA biogenesis pathway. The production of risiRNAs correlates with pre-rRNA processing defects in these mutants. We also show that these risiRNAs are loaded into AGO1, causing reduced loading of miRNAs. This study reveals a previously unknown link between rRNA processing and miRNA accumulation