Miracle-dz/UniFAR-FTUs huggingface dataset:
Adolescent smoking and depression: evidence for self-medication and peer smoking mediation.

AIMS The nature of the relationship between adolescent smoking and depression is unclear and the mechanisms that account for the comorbidity have received little investigation. The present study sought to clarify the temporal precedence for smoking and depression and to determine whether these variables are linked indirectly through peer smoking. PARTICIPANTS The sample was composed of 1093 adolescents participating in a longitudinal study of the behavioral predictors of smoking adoption. DESIGN AND MEASUREMENTS In this prospective cohort study, smoking, depression, peer smoking and other covariates were measured annually from mid-adolescence (9th grade; age 14) to late adolescence (12th grade, age 18). FINDINGS Parallel processes latent growth curve models supported a bidirectional relationship between adolescent smoking and depression, where higher depression symptoms in mid-adolescence (age 14) predicted adolescent smoking progression from mid- to late adolescence (ages 14-18). A significant indirect effect indicated that higher depression symptoms across time predicted an increase in the number of smoking peers, which in turn predicted smoking progression from mid-adolescence to late adolescence. In addition, smoking progression predicted a deceleration of depression symptoms from mid- to late adolescence. A significant indirect effect indicated that greater smoking at baseline predicted a deceleration in the number of smoking peers across time, which predicted a deceleration in depression symptoms from mid-adolescence to late adolescence. CONCLUSIONS The current study provides the first evidence of bidirectional self-medication processes in the relationship between adolescent smoking and depression and highlights peer smoking as one explanation for the comorbidity.
Engineering of mucin-type human glycoproteins in yeast cells

Mucin-type O-glycans are the most typical O-glycans found in mammalian cells and assume many different biological roles. Here, we report a genetic engineered yeast strain capable of producing mucin-type sugar chains. Genes encoding Bacillus subtilis UDP-Gal/GalNAc 4-epimerase, human UDP-Gal/GalNAc transporter, human ppGalNAc-T1, and Drosophila melanogaster core1 β1–3 GalT were introduced into Saccharomyces cerevisiae. The engineered yeast was able to produce a MUC1a peptide containing O-glycan and also a mucin-like glycoprotein, human podoplanin (hPod; also known as aggrus), which is a platelet-aggregating factor that requires a sialyl-core1 structure for activity. After in vitro sialylation, hPod from yeast could induce platelet aggregation. Interestingly, substitution of ppGalNAc-T1 for ppGalNAc-T3 caused a loss of platelet aggregation-inducing activity, despite the fact that the sialyl-core1 was detectable in both hPod proteins on a lectin microarray. Most of O-mannosylation, a common modification in yeast, to MUC1a was suppressed by the addition of a rhodanine-3-acetic acid derivative in the culture medium. The yeast system we describe here is able to produce glycoproteins modified at different glycosylation sites and has the potential for use in basic research and pharmaceutical applications.
Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages

Phagocytes generate nitric oxide (NO) and other reactive oxygen and nitrogen species in large quantities to combat infecting bacteria. Here, we report the surprising observation that in vivo survival of a notorious pathogen—Bacillus anthracis—critically depends on its own NO-synthase (bNOS) activity. Anthrax spores (Sterne strain) deficient in bNOS lose their virulence in an A/J mouse model of systemic infection and exhibit severely compromised survival when germinating within macrophages. The mechanism underlying bNOS-dependent resistance to macrophage killing relies on NO-mediated activation of bacterial catalase and suppression of the damaging Fenton reaction. Our results demonstrate that pathogenic bacteria use their own NO as a key defense against the immune oxidative burst, thereby establishing bNOS as an essential virulence factor. Thus, bNOS represents an attractive antimicrobial target for treatment of anthrax and other infectious diseases.
Original Title: Teaching for understanding at university: Deep approaches and distinctive ways of thinking

Palgrave Macmillan This book was written mainly for teachers in university departments, although it would also be valuable for research students. I read this book from the perspective of a researcher in the particular field who is trying to see “where we are” concerning teaching and learning in HE. The book provides a comprehensive and thorough look at the field of learning and teaching that smoothly brings together educational psychology, pedagogy and education. Throughout the book, the theory and the empirical findings are intertwined comprehensively and the research findings provide a sound basis for the theoretical and practical suggestions for teaching for understanding. Entwistle’s suggestions for teaching for understanding bring to the current literature a fresh pedagogic theoretical look and are thoughtfully accommodated in a scholarly
Both cIAP1 and cIAP2 regulate TNFα-mediated NF-κB activation

The cellular inhibitor of apoptosis 1 and 2 (cIAP1 and cIAP2) proteins have been implicated in the activation of NF-κB by TNFα; however, genetic deletion of either cIAP1 or 2 did not support a physiologically relevant role, perhaps because of functional redundancy. To address this, we used combined genetic and siRNA knockdown approaches and report that cIAP1 and 2 are indeed critical, yet redundant, regulators of NF-κB activation upon TNFα treatment. Whereas NF-κB was properly activated by TNFα in cultured and primary cells deficient in either cIAP1 or 2, removal of both cIAPs severely blunted its activation. After treatment with TNFα, cIAP1 and 2 were rapidly recruited to the TNF receptor 1, along with the adapter protein TNF receptor associated factor 2. Importantly, either cIAP1 or 2 was required for proper TNF receptor 1 signalosome function. In their combined absence, polyubiquitination of receptor interacting protein 1, an upstream event necessary for NF-κB signaling, was attenuated. As a result, phosphorylation of the inhibitor of κB kinase β was diminished, and signal transduction was severely blunted. Consequently, cells missing both cIAP1 and 2 were sensitized to TNFα-mediated apoptosis. Collectively, these data demonstrate that either cIAP1 or 2 is required for proper Rip1 polyubiquitination and NF-κB activation upon TNFα treatment.
The dimensionality of alcohol use disorders and alcohol consumption in a cross-national perspective.

AIMS To replicate the finding that there is a single dimension trait in alcohol use disorders and to test whether the usual 5+ drinks for men and 4+ drinks for women and other measures of alcohol consumption help to improve alcohol use disorder criteria in a series of diverse patients from emergency departments (EDs) in four countries. DESIGN Cross-sectional surveys of patients aged 18 years and older that reflected consecutive arrival at the ED. The Composite International Diagnostic Interview Core was used to obtain a diagnosis of DSM-IV alcohol dependence and alcohol abuse; quantity and frequency of drinking and drunkenness as well as usual number of drinks consumed during the last year. SETTING Participants were 5195 injured and non-injured patients attending seven EDs in four countries: Argentina, Mexico, Poland and the United States (between 1995-2001). FINDINGS Using exploratory factor analyses alcohol use disorders can be described as a single, unidimensional continuum without any clear-cut distinction between the criteria for dependence and abuse in all sites. RESULTS from item response theory analyses showed that the current DSM-IV criteria tap people in the middle-upper end of the alcohol use disorder continuum. Alcohol consumption (amount and frequency of use) can be used in all EDs with the current DSM-IV diagnostic criteria to help tap the middle-lower part of this continuum. Even though some specific diagnostic criteria and some alcohol consumption variables showed differential item function across sites, test response curves were invariant for ED sites and their inclusion would not impact the final (total) performance of the diagnostic system. CONCLUSIONS DSM-IV abuse and dependence form a unidimensional continuum in ED patients regardless of country of survey. Alcohol consumption variables, if added, would help to tap patients with more moderate severity. The DSM diagnostic system for alcohol use disorders showed invariance and performed extremely well in these samples.
Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation.

AIMS To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence. DESIGN Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center. INTERVENTIONS Six weeks of: (i) 0.05 mg nicotine yield cigarettes; (ii) 0.3 mg nicotine yield cigarettes; or (iii) 4 mg nicotine lozenge; 6 weeks of follow-up. Measurements Compensatory smoking behavior, biomarkers of exposure, tobacco dependence, tobacco withdrawal and abstinence rate. FINDINGS Unlike the 0.3 mg cigarettes, 0.05 mg cigarettes were not associated with compensatory smoking behaviors. Furthermore, the 0.05 mg cigarettes and nicotine lozenge were associated with reduced carcinogen exposure, nicotine dependence and product withdrawal scores. The 0.05 mg cigarette was associated with greater relief of withdrawal from usual brand cigarettes than the nicotine lozenge. The 0.05 mg cigarette led to a significantly higher rate of cessation than the 0.3 mg cigarette and a similar rate as nicotine lozenge. CONCLUSION The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.
Characteristics and comorbidity of drug and alcohol-related emergency department presentations detected by nursing triage text.

INTRODUCTION This study used nursing triage text to detect drug- and alcohol-related emergency department (ED) presentations and describe their patient and service delivery characteristics. METHODS Data were reviewed for all ED presentations from 2004 to 2006 (n = 263 937) from two hospitals in Sydney, Australia. Each record included two nursing triage free-text fields, which were searched for more than 100 drug-related and more than 60 alcohol-related terms. Adjusted odds ratios were used to compare the characteristics of drug and alcohol-related ED presentations with all other ED presentation types. RESULTS Just over 5% of ED presentations were identified as alcohol-related and 2% as drug-related. The most prevalent drug-related ED presentations specified were related to amphetamines (18%), heroin (14%), cannabis (14%) and ecstasy (12%), while nearly half (43%) were drug unspecified. Polydrug use was mentioned in 25% of drug-related and 9% of alcohol-related ED presentations, with the highest rate of polydrug use among ecstasy-related (68%) presentations. Drug- and alcohol-related ED presentations were significantly more likely than other ED presentations to have a mental health diagnosis, with the highest rates found among cannabis-related (OR = 7.6) or amphetamine-related (OR = 7.5) presentations. CONCLUSION The ED provides an opportunity for early intervention for patients presenting with comorbid drug and alcohol and mental health problems. Further research is needed to assess the prevalence of drug and alcohol problems in ED patients with mental health problems and to develop effective interventions in that setting.
The effect of changes in drug benefit design among individuals with diabetes in large employer-sponsored insurance plans

THE EFFECT OF CHANGES IN DRUG BENEFIT DESIGN AMONG INDIVIDUALS WITH DIABETES IN LARGE EMPLOYER-SPONSORED INSURANCE PLANS by NINEE SHOUA YANG August 2011 Advisor: Dr. Allen C. Goodman Major: Economics Degree: Doctor of Philosophy With spending for prescription drugs rising so rapidly, employers and insurers are seeking different cost-cutting strategies to stem this tide. Given that prescription drugs have become an indispensable means to treat and manage chronic illnesses, the issues of affordability and trade-offs between medications and other health care services are important for chronically ill patients, particularly for patients with diabetes who typically have more than one comorbidity that require drug therapy, and their health insurance plans. In this dissertation, I analyze the effect of prescription drug cost-shifting via changes in drug benefit design on healthcare expenditure among individuals with diabetes; I take into account the comorbid effect of diabetes for the age population ranging from 18 to 62. Study design, data and organization of the report: This study uses a retrospective research design with observational historical data from the MarketScan Research Database from 2000 to 2001. The subjects are individuals enrolled in large employer-sponsored health insurance plans aged 18 to 62 who were diagnosed with diabetes from 2000 to 2001. The analysis of this study relies on the assumption that changes in spending are caused by changes in the drug benefit plan resulting from the action of employers
Poorly cemented coral reefs of the eastern tropical Pacific: Possible insights into reef development in a high-CO2 world

Ocean acidification describes the progressive, global reduction in seawater pH that is currently underway because of the accelerating oceanic uptake of atmospheric CO2. Acidification is expected to reduce coral reef calcification and increase reef dissolution. Inorganic cementation in reefs describes the precipitation of CaCO3 that acts to bind framework components and occlude porosity. Little is known about the effects of ocean acidification on reef cementation and whether changes in cementation rates will affect reef resistance to erosion. Coral reefs of the eastern tropical Pacific (ETP) are poorly developed and subject to rapid bioerosion. Upwelling processes mix cool, subthermocline waters with elevated pCO2 (the partial pressure of CO2) and nutrients into the surface layers throughout the ETP. Concerns about ocean acidification have led to the suggestion that this region of naturally low pH waters may serve as a model of coral reef development in a high-CO2 world. We analyzed seawater chemistry and reef framework samples from multiple reef sites in the ETP and found that a low carbonate saturation state (Ω) and trace abundances of cement are characteristic of these reefs. These low cement abundances may be a factor in the high bioerosion rates previously reported for ETP reefs, although elevated nutrients in upwelled waters may also be limiting cementation and/or stimulating bioerosion. ETP reefs represent a real-world example of coral reef growth in low-Ω waters that provide insights into how the biological–geological interface of coral reef ecosystems will change in a high-CO2 world.
Computerized detection, segmentation and classification of digital pathology: case study in prostate cancer

OF THE DISSERTATION Computerized Detection, Segmentation and Classification of Digital Pathology: Case Study in Prostate Cancer by Scott Doyle Dissertation Director: Anant Madabhushi Digital pathology refers to the use of scanning hardware and viewing software to digitize samples of stained pathological tissue excised from a patient. Image analysis algorithms can be employed to assist in analyzing these digital samples, increasing the speed and efficiency with which pathology samples are examined in the clinic. Traditionally these algorithms have focused on simple quantification (e.g. cell counting or stain enhancement), but the most recent developments have focused on developing quantitative disease signatures for different tissue types. In this dissertation, an image analysis framework for automated interpretation of histology samples is described using novel image descriptors and new classification techniques. This interpretation of samples has several advantages over the traditional method of manual analysis: (1) by using quantitative disease metrics, it can be applied in a standardized fashion across several institutions with perfect agreement; (2) advanced pattern recognition and machine intelligence algorithms such as supervised classification, intelligent training, and content-based image retrieval can be employed to add to the information used to make a decision regarding diagnosis and treatment; and (3) by providing such an in-depth analysis of tissue, we can make predictions regarding the potential outcome of patients with respect to specific treatment regiments.
Single mutations convert an outward K+ channel into an inward K+ channel

Shaker-type K+ channels in plants display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, an Arabidopsis K+ channel (SKOR) and a tomato K+ channel (LKT1) share high amino acid sequence similarity and identical domain structures; however, SKOR conducts outward K+ current and is activated by positive membrane potentials (depolarization), whereas LKT1 conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the “opposite” voltage-sensing properties of SKOR and LKT1 remains unknown. Using a screening procedure combined with random mutagenesis, we identified in the SKOR channel single amino acid mutations that converted an outward-conducting channel into an inward-conducting channel. Further domain-swapping and random mutagenesis produced similar results, suggesting functional interactions between several regions of SKOR protein that lead to specific voltage-sensing properties. Dramatic changes in rectifying properties can be caused by single amino acid mutations, providing evidence that the inward and outward channels in the Shaker family from plants may derive from the same ancestor.
Broad dispersion and lung localization of virus-specific memory B cells induced by influenza pneumonia

Although memory B cells (BMem) contribute significantly to resistance to infection, BMem population characteristics that may relate to protective efficacy have received little attention. Here, we report a comprehensive quantitative analysis of virus-specific IgG and IgA BMem dispersion after transient influenza pneumonia in mice. From early in the response, BMem circulated continuously and dispersed widely to secondary lymphoid tissues. However, a complicated picture emerged with BMem frequency differences between secondary lymphoid tissues indicating an influence of local tissue factors on trafficking. BMem numbers increased and stabilized at tissue-specific frequencies without contraction of the BMem pool during the period of analysis. The lung was notable as a nonsecondary lymphoid tissue where a rapid influx of IgG and IgA BMem established relatively high frequencies that were maintained long term. Our findings provide insights into the pattern of BMem dispersion, and emphasize the lung as a complex repository of immune memory after local infection.
The importance of family management, closeness with father and family structure in early adolescent alcohol use.

AIMS To examine the importance of family management, family structure and father-adolescent relationships on early adolescent alcohol use. DESIGN Cross-sectional data was collected across 30 randomly selected Australian communities stratified to represent a range of socio-economic and regional variation. SETTING Data were collected during school time from adolescents attending a broad range of schools. PARTICIPANTS The sample consisted of a combined 8256 students (aged 10-14 years). MEASUREMENTS Students completed a web-based survey as part of the Healthy Neighbourhoods project. FINDINGS Family management-which included practices such as parental monitoring and family rules about alcohol use-had the strongest and most consistent relationship with alcohol use in early adolescence. Adolescents reporting higher family management were less likely to have drunk alcohol in their life-time, less likely to drink alcohol in the preceding 30 days and less likely to have had an alcohol binge. Adolescents reporting emotionally close relationships with their fathers were less likely to have drunk alcohol in their life-time and less likely to have had an alcohol binge in the preceding fortnight. CONCLUSIONS Findings indicate that family management practices may contribute to alcohol abstinence in adolescents. Furthermore, emotionally close father-adolescent relationships may also foster abstinence; however, fathers' drinking behaviours need to be considered.
Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome

Fragile X syndrome (FXS) has so far resisted efforts to define the basic cellular defects caused by the absence of a single protein, fragile X mental retardation protein (FMRP), because the patients have a wide variety of symptoms of varying severity. Immature-appearing dendritic spines on neurons found in FXS patients and fmr1-KO mice suggest a role for FMRP in modulating production of synaptic structural proteins. We isolated cortical synaptoneurosomes from WT and KO mice and studied MAPK pathway activation after group I metabotropic glutamate receptor (mGluR) stimulation. Here, we show that ERK in KO synaptoneurosomes is rapidly dephosphorylated upon mGluR1/5 stimulation, whereas it is phosphorylated in WT mice, suggesting that aberrant activation of phosphatases occurs in KO synapses in response to synaptic stimulation. In KO synapses, protein phosphatase 2A (PP2A) is overactivated after mGluR1 stimulation, and tyrosine phosphatase is overactivated after mGluR5 stimulation, causing the rapid deactivation of ERK. ERK activation can be restored in KO by pretreatment with phosphatase blockers; blocking of PP2A by okadaic acid could successfully restore normal ERK activation in KO synaptoneurosomes. We propose that overactivation of phosphatases in synapses may be a key deficit in FXS, which affects synaptic translation, transcription, and synaptic receptor regulation.