Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivo

Enterohemorrhagic E. coli (EHEC) are important foodborne pathogens causing gastroenteritis and more severe complications such as hemorrhagic colitis and hemolytic uremic syndrome. Pathology is most pronounced in the colon, but to date there is no direct clinical evidence showing EHEC binding to colonic epithelium in patients. In this study, we investigated EHEC adherence to the human colon by using in vitro organ culture (IVOC) of colonic biopsies and polarized T84 colon carcinoma cells. We showed for the first time that EHEC colonized human colonic biopsies by forming typical attaching/effacing (A/E) lesions which were dependent on EHEC type III secretion (T3S) and binding of the outer membrane protein intimin to the Translocated intimin receptor (Tir). A/E lesion formation was dependent on oxygen levels and suppressed under oxygen-rich culture conditions routinely used for IVOC. In contrast, EHEC adherence to polarized T84 cells occurred independently of T3S and intimin and did not involve Tir translocation into the host cell membrane. Neither colonization of biopsies nor T84 cells was significantly affected by expression of Shiga toxins. Our study suggests that EHEC colonize and form stable A/E lesions on the human colon which is likely to contribute to intestinal pathology during infection. Furthermore, care needs to be taken when using cell culture models as they might not reflect the in vivo situation

Condoms are more effective when applied by males: a study of young black males in the United States

PurposeTo determine, among a sample of young black male (YBM), whether female application of male condoms for penile–vaginal intercourse would be associated with higher or lower rates of breakage or slippage. A secondary aim was to investigate if higher rates of breakage or slippage were associated with increased odds of acquiring chlamydia and/or gonorrhea.MethodsA cross-sectional study of 412 YBM, aged 15 to 23 years, was conducted in three US cities located in the Southern United States.ResultsAmong YBM reporting frequent female application of condoms, 43.5% reported one or more instance of breakage or slippage, compared with those reporting less frequent female application (27.2%, P = .003). Among YBM reporting one or more event of breakage or slippage, 25.4% tested positive for chlamydia and/or gonorrhea. In contrast, among those not reporting breakage or slippage, 17.2% tested positive (P = .047).ConclusionsFindings suggest that educational and behavioral interventions should seek to improve young women's skills relative to condom application and use. Further studies could also investigate whether intervention efforts should encourage some YBM to be responsible for their own condom application

Normative climates of parenthood across Europe : judging voluntary childlessness and working parents

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)Past research on gender role attitudes has often focused on individual- rather than country-level explanations. Drawing on European Social Survey data from 21 countries, we examine the effect of societal normative climates (i.e., shared perceptions of others’ attitudes) on personal attitudes towards two non-traditional gender roles: Voluntary childlessness and working full-time while children are young. To detect potential gender differences, we analyse disapproval of men and women separately. Findings reveal that there are strong differences in normative climates across countries, and that people generally perceive more disapproval of women than of men for both behaviours. Most importantly, in countries where a higher share of respondents perceives disapproval of these behaviours, respondents themselves disapprove more strongly – even if they do not believe that others disapprove, and even after controlling for other relevant individual- and country-level characteristics. What is more, the independent effect of normative climate explains most of the differences between countries. This robust finding demonstrates the power of country-level normative climates in explaining individuals’ attitudes and between-country differences in attitudes toward gender roles

Genetic analysis of safflower domestication.

BackgroundSafflower (Carthamus tinctorius L.) is an oilseed crop in the Compositae (a.k.a. Asteraceae) that is valued for its oils rich in unsaturated fatty acids. Here, we present an analysis of the genetic architecture of safflower domestication and compare our findings to those from sunflower (Helianthus annuus L.), an independently domesticated oilseed crop within the same family.We mapped quantitative trait loci (QTL) underlying 24 domestication-related traits in progeny from a cross between safflower and its wild progenitor, Carthamus palaestinus Eig. Also, we compared QTL positions in safflower against those that have been previously identified in cultivated x wild sunflower crosses to identify instances of colocalization.ResultsWe mapped 61 QTL, the vast majority of which (59) exhibited minor or moderate phenotypic effects. The two large-effect QTL corresponded to one each for flower color and leaf spininess. A total of 14 safflower QTL colocalized with previously reported sunflower QTL for the same traits. Of these, QTL for three traits (days to flower, achene length, and number of selfed seed) had cultivar alleles that conferred effects in the same direction in both species.ConclusionsAs has been observed in sunflower, and unlike many other crops, our results suggest that the genetics of safflower domestication is quite complex. Moreover, our comparative mapping results indicate that safflower and sunflower exhibit numerous instances of QTL colocalization, suggesting that parallel trait transitions during domestication may have been driven, at least in part, by parallel genotypic evolution at some of the same underlying genes

System FC with Explicit Kind Equality (extended version)

System FC, the core language of the Glasgow Haskell Compiler, is an explicitly-typed variant of System F with first-class type equality proofs called coercions. This extensible proof system forms the foundation for type system extensions such as type families (type- level functions) and Generalized Algebraic Datatypes (GADTs). Such features, in conjunction with kind polymorphism and datatype promotion, support expressive compile-time reasoning. However, the core language lacks explicit kind equality proofs. As a result, type-level computation does not have access to kind- level functions or promoted GADTs, the type-level analogues to expression-level features that have been so useful. In this paper, we eliminate such discrepancies by introducing kind equalities to System FC. Our approach is based on dependent type systems with heterogeneous equality and the “Type-in-Type” axiom, yet it preserves the metatheoretic properties of FC. In particular, type checking is simple, decidable and syntax directed. We prove the preservation and progress theorems for the extended language

System FC with Explicit Kind Equality

System FC, the core language of the Glasgow Haskell Compiler, is an explicitly-typed variant of System F with first-class type equality proofs called coercions. This extensible proof system forms the foundation for type system extensions such as type families (type- level functions) and Generalized Algebraic Datatypes (GADTs). Such features, in conjunction with kind polymorphism and datatype promotion, support expressive compile-time reasoning. However, the core language lacks explicit kind equality proofs. As a result, type-level computation does not have access to kind- level functions or promoted GADTs, the type-level analogues to expression-level features that have been so useful. In this paper, we eliminate such discrepancies by introducing kind equalities to System FC. Our approach is based on dependent type systems with heterogeneous equality and the “Type-in-Type” axiom, yet it preserves the metatheoretic properties of FC. In particular, type checking is simple, decidable and syntax directed. We prove the preservation and progress theorems for the extended language

Visible Type Application

The Hindley-Milner HM type system automatically infers the types at which polymorphic functions are used. In HM, the inferred types are unambiguous, and every expression has a principal type. Type annotations make HM compatible with extensions where complete type inference is impossible, such as higher-rank polymorphism and type-level functions. However, programmers cannot use annotations to explicitly provide type arguments to polymorphic functions, as HM requires type instantiations to be inferred. We describe an extension to HM that allows visible type application. Our extension requires a novel type inference algorithm, yet its declarative presentation is a simple extension to HM. We prove that our extended system is a conservative extension of HM and admits principal types. We then extend our approach to a higher-rank type system with bidirectional type-checking. We have implemented this system in the Glasgow Haskell Compiler and show how our approach scales in the presence of complex type system features

Multiscale Entropy Identifies Postural Control Changes in Persons with Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic auto-immune disorder characterized by demyelination of neurons of the central nervous system. MS-related reductions in neural activity have been associated with reductions in balance control and limitations in mobility. Multiscale entropy (MSE) analysis has been used to identify reductions in complexity of the postural control system in various disorders. The purpose of this study was to examine if center-of-pressure fluctuations, analyzed through MSE, differ between persons with MS and healthy controls. We hypothesized that MSE would be reduced in MS compared to controls in all postural tasks in both anterior-posterior (AP) and medio-lateral (ML) directions. Eight persons with MS (7 female, 1 male) and matched controls completed the testing procedures. The MS subjects had minimal functional impairment (Patient Determined Disease Steps, range 0-3). Quiet standing and fixed distance forward and backward reaches were assessed for 30 s. MSE was computed across 30 time scales (range .01-.25s). Effect size (ES) statistics were used to assess differences between MS and control groups. Quiet standing revealed moderate reductions in complexity among persons with MS compared to controls in the AP direction (ES = .71). The backward reach demonstrated moderate and strong reductions in complexity in the AP and ML direction in the MS group (ES = .74 and 1.0, respectively). Moderate reductions in ML complexity were also observed in the forward reach condition in the MS group (ES = .68). These results support the hypothesis that persons with MS display lower postural complexity compared to those without MS. MSE analysis is a promising new tool for detecting MS-related changes in postural complexity. These changes in postural complexity appear to precede locomotor impairment, as assessed by the patient determined disease steps, and may provide novel insight into MS progression

Using a Video Camera-Based Method to Gather Real World High Beam Usage Data

The majority of traffic fatalities involving pedestrians occur at night and this is largely attributed to low illumination conditions. Yet, drivers tend to underuse their high beams despite the visibility benefits afforded to them. In the present study we report high beam usage rates during an open-road drive using a video camera-based method. Measurements of low and high beam headlamp illuminance were also taken for all vehicles used in this study. The results indicate that drivers, on average, used their high beams 48% of the time possible. Furthermore, there was a moderately negative relationship between low beam output and high beam use indicating that drivers whose low beams produced less illumination tended to use their high beams more often. Future research should empirically investigate this relationship to lend further insight into the mechanism by which beam output influences beam usage. Research that improves our understanding of drivers’ knowledge and use of high beams is likely to be important as headlighting technologies continue to advance

Mechanism of Transforming Growth Factor β–induced Inhibition of T Helper Type 1 Differentiation

Regulation by transforming growth factor (TGF)-β plays an important role in immune homeostasis. TGF-β inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-β blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-β. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor β2 chain is not key to the TGF-β–mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-β on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection