Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse.

Insulin-dependent diabetes mellitus (IDDM) is thought to be an immunologically mediated disease resulting in the complete destruction of the insulin-producing islets of Langerhans. It has become increasingly clear that autoreactive T cells play a major role in the development and progression of this disease. In this study, we examined the role of the CD28/B7 costimulation pathway in the development and progression of autoimmune diabetes in the nonobese diabetic (NOD) mouse model. Female NOD mice treated at the onset of insulitis (2-4 wk of age) with CTLA4Ig immunoglobulin (Ig) (a soluble CD28 antagonist) or a monoclonal antibody (mAb) specific for B7-2 (a CD28 ligand) did not develop diabetes. However, neither of these treatments altered the disease process when administered late, at > 10 wk of age. Histological examination of islets from the various treatment groups showed that while CTLA4Ig and anti-B7-2 mAb treatment blocked the development of diabetes, these reagents had little effect on the development or severity of insulitis. Together these results suggest that blockade of costimulatory signals by CTLA4Ig or anti-B7-2 acts early in disease development, after insulitis but before the onset of frank diabetes. NOD mice were also treated with mAbs to another CD28 ligand, B7-1. In contrast to the previous results, the anti-B7-1 treatment significantly accelerated the development of disease in female mice and, most interestingly, induced diabetes in normally resistant male mice. A combination of anti-B7-1 and anti-B7-2 mAbs also resulted in an accelerated onset of diabetes, similar to that observed with anti-B7-1 mAb treatment alone, suggesting that anti-B7-1 mAb's effect was dominant. Furthermore, treatment with anti-B7-1 mAbs resulted in a more rapid and severe infiltrate. Finally, T cells isolated from the pancreas of these anti-B7-1-treated animals exhibited a more activated phenotype than T cells isolated from any of the other treatment groups. These studies demonstrate that costimulatory signals play an important role in the autoimmune process, and that different members of the B7 family have distinct regulatory functions during the development of autoimmune diabetes

Evolution of cranial shape in a continental‐scale evolutionary radiation of Australian lizards

A defining character of adaptive radiations is the evolution of a diversity of morphological forms that are associated with the use of different habitats, following the invasion of vacant niches. Island adaptive radiations have been thoroughly investigated but continental scale radiations are more poorly understood. Here, we use 52 species of Australian agamid lizards and their Asian relatives as a model group, and employ three‐dimensional geometric morphometrics to characterize cranial morphology and investigate whether variation in cranial shape reflects patterns expected from the ecological process of adaptive radiation. Phylogenetic affinity, evolutionary allometry, and ecological life habit all play major roles in the evolution of cranial shape in the sampled lizards. We find a significant association between cranial shapes and life habit. Our results are in line with the expectations of an adaptive radiation, and this is the first time detailed geometric morphometric analyses have been used to understand the selective forces that drove an adaptive radiation at a continental scale

Co-propagation of maser emission at 1720 and 4765 MHz

MERLIN observations are presented of OH 4765-MHz and OH 1720-MHz masers in the massive star-forming region W3(OH). Two of the three intense spots of maser emission at 4765 MHz are spatially coincident with two similar spots at 1720 MHz in both left-hand circular (LHC) and right-hand circular (RHC) polarizations, to an accuracy of 15 mas. The spots also overlap in velocity when allowance is made for Zeeman splitting of the 1720-MHz line. We conclude that we have found two examples of masers in different rotational levels of OH which are co-propagating through the same column of gas and experiencing competitive gain effects. The third 4765-MHz maser spot was found to have no overlapping counterpart amongst the 1720-MHz masers

Exceptional Indices

Recently a prescription to compute the superconformal index for all theories of class S was proposed. In this paper we discuss some of the physical information which can be extracted from this index. We derive a simple criterion for the given theory of class S to have a decoupled free component and for it to have enhanced flavor symmetry. Furthermore, we establish a criterion for the "good", the "bad", and the "ugly" trichotomy of the theories. After interpreting the prescription to compute the index with non-maximal flavor symmetry as a residue calculus we address the computation of the index of the bad theories. In particular we suggest explicit expressions for the superconformal index of higher rank theories with E_n flavor symmetry, i.e. for the Hilbert series of the multi-instanton moduli space of E_n.Comment: 33 pages, 11 figures, v2: minor correction

Dopamine, appetitive reinforcement, and the neuropsychology of human learning: An individual differences approach

Personality research is usually perceived as lying towards the “softer” end of psychological inquiry, seemingly far from the “harder” neural mechanisms, processes, and neurological lesions which are the daily stuff of neuropsychology. As biologically-oriented personality psychologists, however, we have always tried to couch our proposals in brain- behavioural terms and have even offered suggestions as to the “neuropsychology” of personality traits such as anxiety and their related clinical conditions (e.g., Gray, 1982). Furthermore, several other personality theorists have also drawn from the rich materials of behavioural neuroscience (e.g., Cloninger, Svracik, & Przybeck, 1993; Depue & Collins, 1999; Zuckerman, 1991). In this chapter we continue to apply our neuropsychological approach to personality: specifically focusing on the effects of personality traits on learning tasks

Learning to laugh : children and being human in early modern thought

This essay explores the construction of the human in early modern English thought, and uses discussions of the nature and use of laughter as a distinguishing feature of humanity from classical arguments as well as early modern ones. Using these classical, reformed English discussions of education and of the nature of children reveals an anxiety about the status of the child. Laughing appropriately - using tile mind and not merely the body - is a key feature of being human, and as such, the child's lack of "true' laughter reveals that child's status to be never always-already human. "Human' is a created rather than merely a natural status

Anticholinergic medication use and falls in postmenopausal women: Findings from the women's health initiative cohort study

Background: Results from studies assessing the association between anticholinergic use and falls are mixed, and prior studies are limited in their ability to control for important potential confounders. Thus, we sought to examine the association between anticholinergic medication use, including over-the-counter medications, and recurrent falls in community-dwelling older women. Methods: We analyzed data from a prospective cohort study of women aged 65 to 79 years from the Women's Health Initiative Observational Study and Clinical Trials. Women were recruited between 1993 and 1998, and analyses included 61,451 women with complete information. Medications with moderate or strong anticholinergic effects were ascertained directly from drug containers during face-to-face interviews. The main outcome measure was recurrent falls (≥2 falls in previous year), which was determined from self-report within 1.5 years subsequent to the medication assessment. Results: At baseline, 11.3 % were using an anticholinergic medication, of which antihistamines (commonly available over-the-counter) were the most common medication class (received by 45.2 % of individuals on anticholinergic medication). Using multivariable GEE models and controlling for potential confounders, the adjusted odds ratio for anticholinergic medication use was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple anticholinergic medications had a 100 % increase in likelihood of recurrent falls (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity analysis. Conclusions: Anticholinergic medication use was associated with increased risk for recurrent falls. Our findings reinforce judicious use of anticholinergic medications in older women. Public health efforts should emphasize educating older women regarding the risk of using over-the-counter anticholinergics, such as first-generation antihistamines

Multifunctional photo/thermal catalysts for the reduction of carbon dioxide

The photochemical fixation of CO2 to energy rich products for solar energy storage or feedstock chemicals is an attractive, albeit daunting, challenge. The overall feasibility of CO2 conversion is limited by the availability of efficient photo-active materials that meet the energetic requirements for CO2 reduction and are optically matched to the solar spectrum. Surface modification of TiO2 with earth abundant metal oxides presents one approach to develop visible active photocatalysts through band gap narrowing, while providing catalytic sites to lower the activation energy for CO2 reduction. In this work density functional theory was used to model the effect of surface modification of rutile and anatase using MnOx nanoclusters. The results indicate the formation of inter-band gap states following surface modification with MnOx, but surface water can change this. Oxygen vacancies are predicted to form in supported MnOx and the interaction with CO2 was investigated. MnOx-TiO2 was synthesized and characterised using surface analytical methods and photoelectrochemistry. The interaction of CO2 with the materials under irradiation was probed using in-situ FTIR to interrogate the role of oxygen vacancies in CO2 binding and reaction. These results provide insights into the requirements of a multifunctional catalyst for CO2 conversion