Miracle-dz/UniFAR-FTUs huggingface dataset:
Bully on the Bus.

Discussion questions 1) The first poem on page 1 introduces readers to DJ (the girl bullying Leroy) and to Leroy’s feelings of helplessness. What is it about the poem that helps you know how Leroy is feeling? 2) How does Leroy’s sister, Ruby, try to help him? Why isn’t she more successful? 3) Leroy hasn’t asked for help to deal with the bullying situation. Why do you think he doesn’t want to tell? 4) What are some of the things Leroy does to try to stop DJ from bullying him? 5) What role does the bus driver play in the book? 6) When Ruby and Leroy tell their parents about the bullying situation, how do they respond? 7) Mrs. Wilson gives Leroy some good advice about how to stop the bullying behavior, and together they make a list of ideas that could help. What are the ideas? Do you think it helped that Leroy was involved in the decision making process? 8) How does reading The Big Bad Book of Fairy Tales help Leroy? If you could combine characters from different fairy tales to help prevent bullying, which super character would you create? What would their strengths be? 9) Explore and discuss the theme of courage. How does Leroy find the courage to talk about his problem and then do something about it? 10) What else could Leroy have done if confronting DJ didn’t stop the bullying? 11) Discuss how Leroy’s relationships with others helped him with this situation: • His friends • His teachers at school • His sister, Ruby • His mother and father
Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases. To determine how TREM2 variants contribute to these diseases, we performed structural and functional studies of wild-type and variant proteins. Our 3.1 Å TREM2 crystal structure revealed that mutations found in Nasu-Hakola disease are buried whereas Alzheimer’s disease risk variants are found on the surface, suggesting that these mutations have distinct effects on TREM2 function. Biophysical and cellular methods indicate that Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer’s risk variants impact binding to a TREM2 ligand. Additionally, the Alzheimer’s risk variants appear to epitope map a functional surface on TREM2 that is unique within the larger TREM family. These findings provide a guide to structural and functional differences among genetic variants of TREM2, indicating that therapies targeting the TREM2 pathway should be tailored to these genetic and functional differences with patient-specific medicine approaches for neurodegenerative disorders. DOI: http://dx.doi. org/10.7554/eLife.20391. 001
A new subgroup of the IS 3 family and properties of its representative member IS Ppy 1

Recently, we described a novel insertion element, ISPpy1, isolated from a permafrost strain of Psychrobacter maritimus. In this work, we demonstrated that ISPpy1 is a member of a novel subgroup of the IS3 family of insertion sequences (ISs) that was not identified and characterized previously. IS elements of this subgroup termed the ISPpy1 subgroup are broadly distributed among different taxa of Eubacteria, including Geobacteraceae, Chlorobiaceae, Desulfobacteraceae, Methylobacteriaceae, Nitrosomonadaceae and Cyanobacteria. While displaying characteristic features of the IS3-family elements, ISPpy1 subgroup elements exhibit some unusual features. In particular, most of them have longer terminal repeats with unconventional ends and frameshifting box with an atypical organization, and, unlike many other IS3-family elements, do not exhibit any distinct IS specificity. We studied the transposition and mutagenic properties of a representative member of this subgroup, ISPpy1 and showed that in contrast to the original P. maritimus host, in a heterologous host, Escherichia coli K-12, it is able to translocate with extremely high efficiency into the chromosome, either by itself or as a part of a composite transposon containing two ISPpy1 copies. The majority of transposants carry multiple chromosomal copies (up to 12) of ISPpy1. It was discovered that ISPpy1 is characterized by a marked mutagenic activity in E. coli: its chromosomal insertions generate various types of mutations, including auxotrophic, pleiotropic and rifampicin-resistance mutations. The distribution of IS elements of the novel subgroup among different bacteria, their role in the formation of composite transposons and the horizontal transfer of genes are examined and discussed.
Cytoskeletal Reorganization by G Protein-Coupled Receptors Is Dependent on Phosphoinositide 3-Kinase γ, a Rac Guanosine Exchange Factor, and Rac

ABSTRACT Reorganization of the actin cytoskeleton is an early cellular response to a variety of extracellular signals. Dissection of pathways leading to actin rearrangement has focused largely on those initiated by growth factor receptors or integrins, although stimulation of G protein-coupled receptors also leads to cytoskeletal changes. In transfected Cos-7SH cells, activation of the chemoattractant formyl peptide receptor induces cortical actin polymerization and a decrease in the number of central actin bundles. In this report, we show that cytoskeletal reorganization can be transduced by G protein βγ heterodimers (Gβγ), phosphoinositide 3-kinase γ (PI3-Kγ), a guanosine exchange factor (GEF) for Rac, and Rac. Expression of inactive variants of either PI3-Kγ, the Rac GEF Vav, or Rac blocked the actin rearrangement. Neither wortmannin nor LY294002, pharmacologic inhibitors of PI3-K, could inhibit the actin rearrangement induced by a constitutively active Rac. The inhibition of cytoskeletal reorganization by the dominant negative Vav variants could be rescued by coexpression of a constitutively active form of Rac. In contrast, a Vav variant with its pleckstrin homology (PH) domain missing constitutively induced JNK activation and led to cytoskeletal reorganization, even without stimulation by PI3-Kγ. This suggests that the PH domain of Vav controls the guanosine exchange activity of Vav, perhaps by a mechanism regulated by D3 phosphoinositides generated by PI3-K. Taken together, these findings delineate a pathway leading from activation of a G protein-coupled receptor to actin reorganization which sequentially involves Gβγ, PI3-Kγ, a Rac GEF, and Rac.
Inhibition of Caffeine Metabolism by Estrogen Replacement Therapy in Postmenopausal Women

This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2‐mediated metabolism in postmenopausal women using caffeine as a model substrate. Twelve healthy postmenopausal women underwent estrogen replacement therapy in the form of estradiol (Estrace). Estradiol was initiated at a dose of 0.5 mg a day and titrated to achieve a steady‐state plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR; paraxanthine/ caffeine) were assessed both before and after 8 weeks of estrogen replacement. For the 12 subjects, there was a mean reduction in CMR of −29.2 25.0 (p = 0.0019). Consistent with previous results found in younger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2‐mediated caffeine metabolism.
Identi fi cation of Regions in the Receiver Domain of the ETHYLENE RESPONSE 1 Ethylene Receptor of Arabidopsis Important for Functional Divergence 1 [ OPEN ]

Ethylene influences the growth and development of Arabidopsis (Arabidopsis thaliana) via five receptor isoforms. However, the ETHYLENE RESPONSE1 (ETR1) ethylene receptor has unique, and sometimes contrasting, roles from the other receptor isoforms. Prior research indicates that the receiver domain of ETR1 is important for some of these noncanonical roles. We determined that the ETR1 receiver domain is not needed for ETR1’s predominant role in mediating responses to the ethylene antagonist, silver. To understand the structure-function relationship underlying the unique roles of the ETR1 receiver domain in the control of specific traits, we performed alanine-scanning mutagenesis. We chose amino acids that are poorly conserved and are in regions predicted to have altered tertiary structure compared with the receiver domains of the other two receptors that contain a receiver domain, ETR2 and ETHYLENE INSENSITIVE4. The effects of these mutants on various phenotypes were examined in transgenic, receptor-deficient Arabidopsis plants. Some traits, such as growth in air and growth recovery after the removal of ethylene, were unaffected by these mutations. By contrast, three mutations on one surface of the receiver domain rendered the transgene unable to rescue ethylene-stimulated nutations. Additionally, several mutations on another surface altered germination on salt. Some of these mutations conferred hyperfunctionality to ETR1 in the context of seed germination on salt, but not for other traits, that correlated with increased responsiveness to abscisic acid. Thus, the ETR1 receiver domain has multiple functions where different surfaces are involved in the control of different traits. Models are discussed for these observations.
Natural Variation in Maize Aphid Resistance Is Associated with 2,4-Dihydroxy-7-Methoxy-1,4-Benzoxazin-3-One Glucoside Methyltransferase Activity[C][W]

Susceptibility to corn leaf aphid in maize is associated with changes in defense-inducing maize benzoxazinoid levels, with high HDMBOA-Glc levels and low DIMBOA-Glc levels leading to toxicity but a reduced plant aphid defense response of callose deposition. Variation in HDMBOA-Glc production is due to a transposon insertion that inactivates O-methyltransferases in lines with low HDMBOA-Glc levels. Plants differ greatly in their susceptibility to insect herbivory, suggesting both local adaptation and resistance tradeoffs. We used maize (Zea mays) recombinant inbred lines to map a quantitative trait locus (QTL) for the maize leaf aphid (Rhopalosiphum maidis) susceptibility to maize Chromosome 1. Phytochemical analysis revealed that the same locus was also associated with high levels of 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside (HDMBOA-Glc) and low levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside (DIMBOA-Glc). In vitro enzyme assays with candidate genes from the region of the QTL identified three O-methyltransferases (Bx10a-c) that convert DIMBOA-Glc to HDMBOA-Glc. Variation in HDMBOA-Glc production was attributed to a natural CACTA family transposon insertion that inactivates Bx10c in maize lines with low HDMBOA-Glc accumulation. When tested with a population of 26 diverse maize inbred lines, R. maidis produced more progeny on those with high HDMBOA-Glc and low DIMBOA-Glc. Although HDMBOA-Glc was more toxic to R. maidis than DIMBOA-Glc in vitro, BX10c activity and the resulting decline of DIMBOA-Glc upon methylation to HDMBOA-Glc were associated with reduced callose deposition as an aphid defense response in vivo. Thus, a natural transposon insertion appears to mediate an ecologically relevant trade-off between the direct toxicity and defense-inducing properties of maize benzoxazinoids.
The quest for a mechanistic understanding of biodiversity–ecosystem services relationships

Ecosystem services (ES) approaches to biodiversity conservation are currently high on the ecological research and policy agendas. However, despite a wealth of studies into biodiversity's role in maintaining ES (B–ES relationships) across landscapes, we still lack generalities in the nature and strengths of these linkages. Reasons for this are manifold, but can largely be attributed to (i) a lack of adherence to definitions and thus a confusion between final ES and the ecosystem functions (EFs) underpinning them, (ii) a focus on uninformative biodiversity indices and singular hypotheses and (iii) top-down analyses across large spatial scales and overlooking of context-dependency. The biodiversity–ecosystem functioning (B–EF) field provides an alternate context for examining biodiversity's mechanistic role in shaping ES, focusing on species' characteristics that may drive EFs via multiple mechanisms across contexts. Despite acknowledgements of a need for B–ES research to look towards underlying B–EF linkages, the connections between these areas of research remains weak. With this review, we pull together recent B–EF findings to identify key areas for future developments in B–ES research. We highlight a means by which B–ES research may begin to identify how and when multiple underlying B–EF relationships may scale to final ES delivery and trade-offs.
Emotion Recognition and Psychosis-Proneness: Neural and Behavioral Perspectives

Schizophrenia is associated with deficits in social cognition and emotion processing, but it is not known how these deficits relate to other domains of neurocognition and whether they might contribute to psychosis development. The current dissertation approaches this question by looking at the relationship between psychosis proneness and face emotion recognition ability, a core domain of social-emotional processing. Psychosis proneness was inferred by the presence of psychosis-like characteristics in otherwise healthy individuals, using self-report measures. Face emotion recognition ability was found to be associated with psychosis-proneness across four large web-based samples and one lab sample. These associations were relatively specific, and could not be explained by differences in face processing or IQ. Using functional magnetic resonance imaging (fMRI), psychosis-proneness was linked with reduced neural activity in brain regions that underlie normal face emotion recognition, including regions that are implicated in self-representation. Additional experiments were conducted to explore psychosis-proneness related differences in self-representation, and a relationship was revealed between cognitive-perceptual (positive) dimensions of psychosis-proneness and (1) flexibility in the body representation (as measured by the rubber hand illusion), and (2) self-referential source memory (but not self-referential
Aging and Schizophrenia: Current Health Services Research and Recommendations

Little is known about the functioning and health care use of older patients with schizophrenia. Understanding the use patterns of older patients with schizophrenia, a rapidly growing population, will inform health care planners and policy makers who make decisions about resource allocation and program development. The results are presented from a large-scale study to examine the relationship between age and the use of health services and level of functioning in patients with schizophrenia. Older adults with schizophrenia experienced fewer psychiatric hospitalizations but, once hospitalized, had longer inpatient stays. In contrast, older patients had fewer outpatient psychiatric visits and more medical outpatient visits and medical hospitalizations than younger individuals. The relatively lower use of outpatient psychiatric care by older patients with schizophrenia suggests that there may be barriers to accessing these services. When older patients are hospitalized for psychiatric reasons, their stays are longer. The implications of these findings are discussed.
The Impact of Sociotechnical Task Demands on Use of Worker Discretion and Functional Skill

This research applies theoretical propositions from macro-organizational research to the level of task-based work as performed by individual workers. A model, theoretical propositions, and testable hypotheses are developed which relate sociotechnical demand to decisional discretion and worker skill at the task level. Measures of sociotechnical demand are developed for the purpose of this research and the remaining measures of decisional discretion and worker skill are taken from the Functional Job Analysis system. An archival set of 100 tasks from a wide variety of jobs was rated by trained raters on measures of sociotechnical demand, decisional discretion, and worker skill. Analysis of these ratings provided generally good support for our theoretical predictions, with decisional discretion mediating the impact of both technological and social demands on cognitive skill. Complexity of social skill increased exponentially as a function of greater social demand, suggesting some important implications for labor economic theory and analysis. The results provided a strong empirical validation of the Functional Job Analysis model. Implications of the findings for social scientists, human resource planners, government policy makers, and human resource specialists are discuss
Risk factors for injury in rugby union football in New Zealand: a cohort study

Objective To identify risk factors for injury in amateur club rugby. Design Prospective cohort design; with follow-up over the 2004 season. Setting Amateur club rugby in New Zealand. Participants Seven hundred and four male rugby players, aged 13 years and over. Assessment of risk factors The study investigated the independent effect on injury incidence of age, ethnicity, rugby experience, height, weight, body mass index, physical activity, cigarette smoking, previous injury, playing while injured, grade, position, training, time of season, warm-up, foul play, weather conditions, ground conditions and protective equipment. Generalised Poisson regression was used to estimate the effect of each factor after adjusting for all other factors. Main outcome measures Game injury, defined as ‘any event that resulted in an injury requiring medical attention or causing a player to miss at least one scheduled game or team practice’. Results A total of 704 players, representing 6263 player-games, contributed information on injury and exposure. Evidence was obtained of the effect on injury incidence of increasing age, Pacific Island versus Maori ethnicity (injury rate ratio (IRR)=1.48, 1.03–2.13), ≥40 h strenuous physical activity per week (IRR=1.54, 1.11–2.15), playing while injured (IRR=1.46, 1.20–1.79), very hard ground condition (IRR=1.50, 1.13–2.00), foul-play (IRR=1.87, 1.54–2.27) and use of headgear (IRR=1.23, 1.00–1.50). Conclusions Opportunities for injury prevention might include promoting injury-prevention measures more vigorously among players of Pacific Island ethnicity, ensuring injured players are fully rehabilitated before returning to play, reducing the effects of ground hardness through ground preparation and stricter enforcement of the laws relating to foul play.
Correlation Neglect in Belief Formation

Many information structures generate correlated rather than mutually independent signals, the news media being a prime example. This paper shows experimentally that in such contexts many people neglect these correlations in the updating process and treat correlated information as independent. In consequence, people's beliefs are excessively sensitive to well-connected information sources, implying a pattern of "overshooting" beliefs. Additionally, in an experimental asset market, correlation neglect not only drives overoptimism and overpessimism at the individual level, but also affects aggregate outcomes in a systematic manner. In particular, the excessive confidence swings caused by correlated signals give rise to predictable price bubbles and crashes. These findings are reminiscent of popular narratives according to which aggregate booms and busts might be driven by the spread of "stories". Our results also lend direct support to recent models of boundedly rational social learning.
Model-based classification trees

The construction of classification trees is nearly always top-down, locally optimal, and data-driven. Such recursive designs are often globally inefficient, for instance, in terms of the mean depth necessary to reach a given classification rate. We consider statistical models for which exact global optimization is feasible, and thereby demonstrate that recursive and global procedures may result in very different tree graphs and overall performance.
Twin concordance and sibling recurrence rates in multiple sclerosis

Size and ascertainment constraints often limit twin studies to concordance comparisons between identical and fraternal twins. Here we report the final results of a longitudinal, population-based study of twins with multiple sclerosis (MS) in Canada. Bias was demonstrably minimized, and an estimated 75% of all Canadian MS twin pairs were ascertained, giving a sample sufficiently large (n = 370) to permit additional informative comparisons. Twinning was not found to affect prevalence, and twins with MS did not differ from nontwins for DR15 allele frequency nor for MS risk to their siblings. Probandwise concordance rates of 25.3% (SE ± 4.4) for monozygotic (MZ), 5.4% (±2.8) for dizygotic (DZ), and 2.9% (±0.6) for their nontwin siblings were found. MZ twin concordance was in excess of DZ twin concordance. The excess concordance in MZ was derived primarily from like-sexed female pairs with a probandwise concordance rate of 34 of 100 (34 ± 5.7%) compared with 3 of 79 (3.8 ± 2.8%) for female DZ pairs. We did not demonstrate an MZ/DZ difference in males, although the sample size was small. We observed a 2-fold increase in risk to DZ twins over nontwin siblings of twins, but the difference was not significant.
Temperature Effect on the Nanostructure of SDS Micelles in Water

Sodium dodecyl sulfate (SDS) surfactants form micelles when dissolved in water. These are formed of a hydrocarbon core and hydrophilic ionic surface. The small-angle neutron scattering (SANS) technique was used with deuterated water (D2O) in order to characterize the micelle structure. Micelles were found to be slightly compressed (oblate ellipsoids) and their sizes shrink with increasing temperature. Fits of SANS data to the Mean Spherical Approximation (MSA) model yielded a calculated micelle volume fraction which was lower than the SDS surfactant (sample mixing) volume fraction; this suggests that part of the SDS molecules do not participate in micelle formation and remain homogeneously mixed in the solvent. A set of material balance equations allowed the estimation of the SDS fraction in the micelles. This fraction was found to be high (close to one) except for samples around 1 % SDS fraction. The micelle aggregation number was found to decrease with increasing temperature and/or decreasing SDS fraction.
Medium-chain fatty acids increase glucose production in normal and low birth weight newborns.

To study the pathogenesis of hypoglycemia in low birth weight infants, glucose production was measured in five hypotrophic and four premature newborns with glycemia of 45 +/- 6 and 59 +/- 10 mg/dl, respectively. Hepatic glucose output averaged 5.7 +/- 0.4 and 5.3 +/- 0.5 mg.kg-1.min-1 in these neonates vs. 8.2 +/- 0.5 mg.kg-1.min-1 in five normal at term newborns and was correlated with glycemia (P less than 0.02). Despite normal plasma free fatty acids, the low birth weight infants had low ketone levels of 163 +/- 72 and 126 +/- 65 vs. 263 +/- 60 microM in normals. Oral administration of medium-chain triglycerides to the neonates increased their circulating ketones by two- to threefold and restored near-normal glycemia (51 +/- 9 and 76 +/- 8 mg/dl) and production of glucose (6.7 +/- 0.7 and 6.6 +/- 0.8 mg.kg-1.min-1) in the hypotrophic and premature vs. normals (8.7 +/- 0.7 mg.kg-1.min-1). Individual rates of glucose production correlated with ketone concentrations (P less than 0.02). We conclude that the hypoglycemia characterizing low birth weight neonates is primarily due to impaired glucose production. That exogenous lipids were able to increase glucose production indicates that fatty acid oxidation plays an important glucoregulatory role in the human newborn.