Logic motif of combinatorial control in transcriptional networks

Combinatorial control is prevalent in transcriptional regulatory networks. However, whether there are specific logic patterns over- or under-represented in real networks remains uninvestigated. Using a theoretic model and _in-silico_ simulations, we systematically study how the relative abundance of distinct regulatory logic patterns influences the network’s global dynamics. We find that global dynamic characteristics are sensitive to several specific logic patterns regardless of the detailed network topology. We show it is possible to infer logic motifs based on the sensitivity profile and the biological interpretations of these global characteristics

Factors associated with one year retention to methadone maintenance treatment program among patients with heroin dependence in China

Abstract Objective The aim of this study was to evaluate the risk factors associated with dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow-up cohort study in China. Methods A data analysis is to explore the adherence of MMT during one year from three hundred and twenty patients with heroin dependence at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were from the part of China-United States cooperation project entitled “Research about improving the compliance and efficacy of methadone maintenance treatment in China”. Our data analysis includes the patients’ attendance in the 6 months clinical study and the data in another 6 months afterward. The data of patients at baseline were collected with the Addiction Severity Index (ASI) which is a semi-structured questionnaire covering socio-demographic characteristics and drug use history. The one year attendance after recruitment at the clinics and daily dose were abstracted from the MMT clinic register system. The Cox proportional hazards model were used to explore the risk factor of dropout, defined as seven consecutive days without methadone. Results By the end of 1 year of treatment 86 patients still remained in MMT without dropout (87% in Shanghai and 13% patients in Kunming). Over the entire 1-year period the median days of remaining in the program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The factors associated with retention included age (HR = 0.98, 95%C.I.:0.96-0.99, P = 0.0062) and ASI alcohol scores (HR = 5.72, 95%C.I.:1.49-21.92, P = 0.0109) at baseline. Conclusion One year retention of newly recruited patients with heroin dependence was related to age and ASI alcohol scores at baseline. The adherence is poorer for the patients who are young and having more serious alcohol problems.http://deepblue.lib.umich.edu/bitstream/2027.42/109460/1/13011_2013_Article_286.pd

Psychometric Properties of the Chinese version of UPPS-P Impulsive Behavior Scale.

OBJECTIVE: The present study aimed to assess the psychometric properties of a Chinese version of the UPPS-P Impulsive Behavior Scale. The associations between the UPPS-P scale and impulsivity choice, gender, smoking, and drinking status were also assessed. METHODS: A total of 127 adults ranging from 21 to 65 years old participated in the study. Participants were administered with the Chinese version of the UPPS-P Impulsive Behavior Scale, Beck Depression Inventory II (BDI-II), and State-Trait Anxiety Inventory (STAI). Impulsivity choice tasks were also tested including the Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART), and Beads Task (Beads). RESULTS: A new version of the UPPS-P Impulsive Behavior Scale was formed that includes 40 items. The scores of the UPPS-P Impulsive Behavior Scale demonstrated adequate internal consistency on five subscales but less sufficient structure validity in the present sample. In addition, positive urgency was negatively related to the Beads task; negative urgency and positive urgency were positively related to the DDT and BART. Moreover, positive and negative urgency were positively correlated with depression; all five subscales were positively correlated with anxiety; sensation seeking was higher in males than females and in alcohol drinkers than non-drinkers; and lack of premeditation and lack of perseverance were higher in nonsmokers than smokers. CONCLUSIONS: The present study supports the reliability but not the structure validity of the UPPS-P Impulsive Behavior Scale. The impulsivity personality trait assessed by the UPPS-P scale was associated with impulsivity choice, depression, anxiety, gender, and drinking and smoking status. Further studies should be conducted to explore the structure of impulsivity in the Chinese population

Impulsivity and craving in subjects with opioid use disorder on methadone maintenance treatment.

BACKGROUND: Methadone maintenance treatment (MMT) is effective in decreasing opioid use or facilitating abstinence. Previous studies using small opioid use disorder samples suggest that cognitive impairments including impulsivity and executive functions may partially improve on MMT, but a range of deficits may persist. However, systematic assessments with larger samples are needed to confirm the profile of cognitive functions on MMT. METHODS: We assessed four types of impulsivity (delay discounting, reflection impulsivity, risk taking and motoric impulsivity), executive functioning (spatial working memory, paired associative learning and strategic planning) and drug cue-induced craving in a relatively large population (115 MMT patients, 115 healthy controls). The relationships between impulsivity, drug cue-induced craving and addiction-related variables were also assessed. RESULTS: Delay discounting, as well as drug cue-induced craving was increased in patients, while motoric impulsivity was lower than in controls. Paired associative learning was additionally impaired, which was explained by increased depression and anxiety levels in patients. Within the MMT group, the delay discounting and drug-cue induced craving scores were positively correlated with self-reported urgency, but unrelated to methadone dosage, duration on methadone, withdrawal symptoms, or presence of nicotine dependence. CONCLUSIONS: Our findings highlight increased delay discounting and cue-induced craving in MMT patients suggesting a potential role for trait effects in delay discounting. Although previous smaller studies have shown impaired executive function, in our large sample size on chronic MMT we only observed impaired associative learning related to depressive and anxiety symptoms highlighting a role for managing comorbid symptoms to further optimize cognitive function

Curvature effect on surface topography and uniform scallop height control in normal grinding of optical curved surface considering wheel vibration

© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. High-precision optical components with complex shapes or microstructures have been extensively used in numerous fields such as biomedicine, energy and aerospace. In order to accurately achieve the specific functions of the components, the form accuracy and uniform surface quality need to reach an ever-high level. To achieve this, ultra-precision normal grinding is used for machining various types of complex optical surfaces. However, the intricate variation of the workpiece curvature and grinding wheel vibration gives rise to great challenges to obtain higher precision and uniform surface conditions. In this study, the influence of curvature on surface topography generation has been investigated and a novel model of scallop height has been developed for surface topography generation in the normal grinding of the curved surface. In addition, the relative influence of the curvature is analyzed experimentally, in which the micro-waviness generation as a consequence of the unbalanced vibration of the grinding wheel is modeled and validated by experiments. Finally, the micro sinusoidal array with the setting value for scallop height is achieved by controlling the feed speed, which is determined by the local curvature of surface profile. The results indicated that the curvature variation posed a significant effect on surface uniformity and the model is valid to achieve surface scallop height control in the normal grinding effectively

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China

Transcriptomics and metabolomics reveal the primary and secondary metabolism changes in Glycyrrhiza uralensis with different forms of nitrogen utilization

The roots and rhizomes of Glycyrrhiza uralensis Fisch. represent the oldest and most frequently used herbal medicines in Eastern and Western countries. However, the quality of cultivated G. uralensis has not been adequate to meet the market demand, thereby exerting increased pressure on wild G. uralensis populations. Nitrogen, vital for plant growth, potentially influences the bioactive constituents of plants. Yet, more information is needed regarding the effect of different forms of nitrogen on G. uralensis. G. uralensis seedlings were exposed to a modified Hoagland nutrient solution (HNS), varying concentrations of nitrate (KNO3), or ammonium (NH4)2SO4. We subsequently obtained the roots of G. uralensis for physiology, transcriptomics, and metabolomics analyses. Our results indicated that medium-level ammonium nitrogen was more effective in promoting G. uralensis growth compared to nitrate nitrogen. However, low-level nitrate nitrogen distinctly accelerated the accumulation of flavonoid ingredients. Illumina sequencing of cDNA libraries prepared from four groups—treated independently with low/medium NH4+ or NO3- identified 364, 96, 103, and 64 differentially expressed genes (DEGs) in each group. Our investigation revealed a general molecular and physiological metabolism stimulation under exclusive NH4+ or NO3- conditions. This included nitrogen absorption and assimilation, glycolysis, Tricarboxylic acid (TCA) cycle, flavonoid, and triterpenoid metabolism. By creating and combining putative biosynthesis networks of nitrogen metabolism, flavonoids, and triterpenoids with related structural DEGs, we observed a positive correlation between the expression trend of DEGs and flavonoid accumulation. Notably, treatments with low-level NH4+ or medium-level NO3- positively improved primary metabolism, including amino acids, TCA cycle, and glycolysis metabolism. Meanwhile, low-level NH4+ and NO3- treatment positively regulated secondary metabolism, especially the biosynthesis of flavonoids in G. uralensis. Our study lays the foundation for a comprehensive analysis of molecular responses to varied nitrogen forms in G. uralensis, which should help understand the relationships between responsive genes and subsequent metabolic reactions. Furthermore, our results provide new insights into the fundamental mechanisms underlying the treatment of G. uralensis and other Glycyrrhiza plants with different nitrogen forms

Overexpression of Na ؉ -Dependent Myo-inositol Transporter Gene in Mouse Lens Led to Congenital Cataract

PURPOSE. Maintaining appropriate osmotic pressure is essential for maintaining lens transparency. This study was performed to investigate whether high levels of myo-inositol, one of the major organic osmolytes in the lens, would lead to cataract development. METHODS. Transgenic mouse lines carrying the bovine Na ϩ -dependent myo-inositol transporter (bSMIT) cDNA under the control of the mouse ␣A-crystallin promoter were generated. RESULTS. Increased bSMIT expression was accompanied by increased myo-inositol level in the lens and increased uptake of ( 3 H) myo-inositol by the lens in culture. The transgenic mice developed observable cataract under normal rearing conditions beginning at 2 to 8 weeks of age, and the severity of cataract development was correlated to the level of bSMIT gene expression and lens myo-inositol accumulation. For transgenic mouse line 3352, heterozygous mice did not develop cataract, whereas homozygous ones did. Prenatal feeding of heterozygous 3352 mice with high myo-inositol diet led to cataract development, indicating that cataract development was not merely due to a nonspecific effect of SMIT overexpression. Introducing aldose reductase overexpressing transgene into heterozygous 3352 mice also led to cataract development, indicating that this type of cataract is primarily due to osmotic stress. CONCLUSIONS. The present results indicate that high levels of myo-inositol and sorbitol in the lens contribute to cataract development. This is a useful model to study the role of osmotic stress in cataractogenesis during lens development. (Invest Ophthalmol Vis Sci. 2000;41:1467-1472 C ataract is the most important cause of blindness in the world. Nearly 16 million people are estimated to be blind because of cataract. 1 There are a number of causes for cataract, including congenital cataract, cataract from infection, cataract from UV and X-ray irradiation and oxidation damage, and cataract associated with several diseases, particularly diabetes. The transparency in mammalian lenses is due to the presence of crystallin structures formed by highly ordered association of several proteins. Changes in ionic environment, a reduction in the level of antioxidants such as reduced glutathione and ascorbic acid, and changes in the level of other solutes may lead to random protein aggregation and disruption of the crystallin structures, resulting in lens opacity and cataract. Therefore, the lens needs to stabilize the intracellular osmotic pressure by regulating the influx and efflux of water, osmolytes, and other solutes. Osmotic stress due to the accumulation of sorbitol in the lens is most likely the cause of diabetic cataract. This is based on the fact that sorbitol accumulates to high levels in the lenses of diabetic animals 6 Development of lens opacity in vitro can be prevented by AR inhibitors or if the medium is made hypertonic to balance the increased sorbitol accumulation in the lens, indicating that osmotic stress is the cause of diabetic cataract. 9 To determine whether cataract caused by sorbitol accumulation is a consequence of osmotic stress rather than the toxic effect of sorbitol, we wanted to increase the lens myoinositol (MI) level to see if that also causes cataract. Myoinositol is one of the three major osmolytes in the lens besides sorbitol and taurine. 10 Influx of MI into lens is dependent on the Na ϩ -dependent MI transporter (SMIT). 11 In this study, we produced transgenic mice that overexpress SMIT constitutively in lens cells and found that they developed congenital cataract under normal rearing condition beginning at 2 to 8 weeks of age. These results provide strong evidence that a high level o