Psychomotor Function in Chronic Daily Cannabis Smokers during Sustained Abstinence

Background

The present study assessed psychomotor function in chronic, daily cannabis smokers during 3 weeks continuously monitored abstinence on a secure research unit. We hypothesized that psychomotor performance would improve during abstinence of chronic, daily cannabis smokers.

Methodology/Principal Findings

Performance on the critical tracking (CTT) and divided attention (DAT) tasks was assessed in 19 male chronic, daily cannabis smokers at baseline and after 8, 14–16 and 21–23 days of continuously monitored abstinence. Psychomotor performance was compared to a control group of non-intoxicated occasional drug users. Critical frequency (λ_c) of the CTT and tracking error and control losses of the DAT were the primary outcome measures. Results showed that chronic cannabis smokers’ performance on the CTT (p<0.001) and the DAT (p<0.001) was impaired during baseline relative to the comparison group. Psychomotor performance in the chronic cannabis smokers improved over 3 weeks of abstinence, but did not recover to equivalent control group performance.

Conclusions/Significance

Sustained cannabis abstinence moderately improved critical tracking and divided attention performance in chronic, daily cannabis smokers, but impairment was still observable compared to controls after 3 weeks of abstinence. Between group differences, however, need to be interpreted with caution as chronic smokers and controls were not matched for education, social economic status, life style and race.     

Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.     

狗牙根与牛鞭草在三峡库区消落带水淹结束后的抗氧化酶活力

三峡水库周期性水淹结束后,消落带植物积极恢复生长的能力有利于其生存和定居,因此,探究影响植物恢复生长的关键生理生态机制对于消落带生态治理具有重要意义。采用野外采样、对比测定的手段,研究了生长于三峡水库消落带的狗牙根和牛鞭草根系在冬季水淹结束后清除活性氧(ROS)的关键酶活力恢复动态。结果表明:与对照相比,经历水淹的植物恢复初期发生明显氧化胁迫,超氧化歧化酶(SOD)、抗坏血酸过氧化物酶(APX)均维持了水淹诱导增加的活力水平。两个物种的过氧化氢酶(CAT)在水淹中活力均较低;出露之后后狗牙根CAT趋向于对照水平,牛鞭草CAT活力迅速上升但未到显著水平。水淹结束后24 d各个酶活力均回复到对照水平,表明氧化胁迫已基本消失。消落带位点植物不同酶活力之间表现出显著的相关关系,这可能是植株维持ROS代谢内稳态的表现。     

MiR-143 enhances adipogenic differentiation of 3T3-L1 cells through targeting the coding region of mouse pleiotrophin

Adipogenic differentiation of preadipocytes is a complex process regulated by various factors including miRNAs and cytokines. MiR-143 is a well known miRNA that enhances adipogenesis. Pleiotrophin (PTN), a heparin-binding growth factor, plays a negative role in adipogenesis. In this investigation, we demonstrate that PTN is a target gene of miR-143 during adipogenic differentiation in 3T3-L1 preadipocytes. MiR-143 down regulates PTN expression through interaction with a target site of miR-143 in the coding region of mouse PTN. The rare codons upstream of the target site regulate miR143-induced translational knockdown of PTN, which provides more insight into the mechanism of adipogenic differentiation.     

A dilution-filtration system for removing cryoprotective agents

In most cryopreservation applications, the final concentrations of cryoprotective agents (CPAs) must be reduced to biocompatible levels. However, traditional methods for removing CPAs usually have disadvantages of operation complexity, time consumption, and ease of contamination, especially for the applications involving large volumes of cell suspensions. A dilution-filtration system, which involves pure ultrafiltration for separation, was developed for continuous, automatic, and closed process of removing CPAs. To predict the optimal protocols under given experimental conditions, a theoretical model was established first. Cell-free experiments were then conducted to investigate the variation in CPA concentration during the process, and the experimental data were compared with the theoretical values for the validation of the model. Finally, ten units (212.9?ml/unit±9.5?ml/unit) of thawed human red blood cells (cryopreserved with 40% (w/v) glycerol) were deglycerolized using the theoretically optimal operation protocols to further validate the effectiveness and advantage of the system. In the cell-free experiments, glycerol was continuously removed and the concentration variations fitted the simulated results quite well. In the in-vitro experiments, glycerol concentration in RBC suspension was reduced to 5.57?g/l±2.81?g/l within an hour, and the cell count recovery rate was 91.19%±3.57%, (n=10), which proves that the system is not only safe for removing CPAs, but also particularly efficient for processing large-scale samples. However, the operation parameters must be carefully controlled and the optimal protocols should be specialized and various from case to case. The presented theoretical model provides an effective approach to find out the optimal operation protocols under given experimental conditions and constrains.     

Structural determinants of caspase-9 inhibition by the vaccinia virus protein, F1L

In multicellular organisms, apoptosis is a powerful method of host defense against viral infection. Apoptosis is mediated by a cascade of caspase-family proteases that commit infected cells to a form of programmed cell death. Therefore, to replicate within host cells, viruses have developed various strategies to inhibit caspase activation. In the mitochondrial cell-death pathway, release of cytochrome c from mitochondria into the cytosol triggers assembly of the oligomeric apoptosome, resulting in dimerization and activation of the apical caspase-9 (C9), and in turn its downstream effector caspases, leading to apoptosis. We previously showed that the vaccinia virus-encoded Bcl-2-like protein, F1L, which suppresses cytochrome c release by binding Bcl-2 family proteins, is also a C9 inhibitor. Here, we identify a novel motif within the flexible N-terminal region of F1L that is necessary and sufficient for interaction with and inhibition of C9. Based on functional studies and mutagenesis, we developed an atomic model of the complex in which F1L inhibits C9 by engaging the active site in the reverse orientation with respect to substrate peptides, in a manner analogous to that of XIAP-mediated inhibition of caspases-3 and -7. These studies offer new insights into the mechanism of apoptosome inhibition by F1L as well as novel probes to understand the molecular bases of apoptosome regulation and turnover. They also suggest how the two distinct functionalities of F1L (inhibition of C9 and suppression of pro-apoptotic Bcl-2 family proteins) may operate in a cellular setting.     

Altered expression levels of miRNAs in serum as sensitive biomarkers for early diagnosis of traumatic injury

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides in length which regulate gene expression negatively and play important roles in many pathological processes. It has been demonstrated that circulating miRNAs hold promise to serve as practicable molecular markers for diverse physiological and pathological conditions. In this investigation, we chose partial hepatectomy (PH) as traumatic injury model. There were significantly differential expression of miRNAs in rat serum post-traumatic injury (21 miRNAs were more than twofold up-regulated). Especially, the expression of miR-9 showed the highest up-regulated (>70-fold), and it possessed the characteristics of biomarker that was more sensitive than aspartate aminotransferase and alanine aminotransferase and C-reactive protein for traumatic liver injury. There was also a prominent increase in the expression levels of miR-9 in different brain areas after traumatic injury. Our data suggest that serum miR-9 may serve as promising biomarker for traumatic injury with high sensitivity. Furthermore, these findings may help to elucidate the complex network which mediates stress response to traumatic injury.     

克隆整合提高淹水胁迫下狗牙根根部的活性氧清除能力

虽然国内外已开展大量关于克隆整合影响植物抗逆生理的研究,但迄今未见克隆整合是否会影响逆境下不同分株清除活性氧过程的报道。以河岸带适生克隆植物狗牙根(Cynodon dactylon)为例,研究克隆植物的抗氧化生理响应,检测了狗牙根在先端淹水/不淹水、先端与基端匍匐茎连接/切断两个因素的交互作用下的根部主要抗氧化酶:超氧化岐化酶(Superoxide dismutase, SOD)、抗坏血酸过氧化物酶(Ascorbate peroxidase, APX)、过氧化氢酶(Catalase, CAT)的活力以及生物量的变化。结果显示,淹水环境中狗牙根先端的生物量和根部SOD酶活力在匍匐茎连接处理下显著高于切断处理组,同一处理的生物量以及根部APX、CAT酶活力总体上表现出不同程度的提高趋势;与受淹先端连接的基端分株根部抗氧化酶活力均低于切断处理组,且SOD和CAT受连接处理影响显著;淹水和切断处理显著降低先端分株的生物量,但对基端和克隆片段影响不明显。这表明淹水胁迫下克隆整合提高了其根部活性氧清除能力,显著改善了先端分株的表现。