STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE : II. THE RELATION BETWEEN HEMAGGLUTINATING ANTIBODY AND GRAFT RESISTANCE IN THE NORMAL MOUSE AND MICE PRETREATED WITH TISSUE PREPARATIONS

The relation between serum antibody and resistance to tumor homografts in the mouse has been investigated. Production of serum antibody in response to homografts of a transplantable sarcoma (Sarcoma 1) was demonstrated, by cytotoxic action on the cells of the tumor, and also by a hemagglutinin test. The simpler and more repeatable hemagglutinin test was further investigated. Peak hemagglutinin titres were reached after the immunizing homografts underwent breakdown. Following transfer of lymph node cells from immunized mice into hosts of the same strain, hemagglutinin could be detected in the host serum. The course of its production showed that this secondary antibody was not elicited by transferred antigen, nor could it be due to transfer of preformed antibody. The cells developed the capacity to transfer hemagglutinin production later than the power to transfer heightened graft resistance. Spleen cells also transferred hemagglutinin production, at a later stage after immunization and to a lesser extent than cells from the regional lymph nodes. Implantation of the sarcoma in mice pretreated with certain preparations of lyophilized or frozen tissue stimulated hemagglutinin production, although the tumor grew progressively. The regional lymph nodes participated in the response: they could transfer hemagglutinin production into secondary hosts, but not graft resistance, and indeed appeared to diminish resistance. Lymph node cells from immunized donors conferred protection against the tumor on pretreated mice. Lymph nodes from normal donors also appeared in some experiments to confer protection although the effect was obscured by the rapidity with which the growing tumor became immunologically invulnerable. The fate of lymph node cells stained with acriflavine was followed after transfer. No effect of the staining on the power of the cells to confer immunity could be detected. Cells transferred to the peritoneal cavity passed into various host tissues, but were not found in test homografts. The conclusion is drawn that the hemagglutinating antibody is distinct from the antibody effective in combating homografts. The similarity in this respect between the homograft reaction and sensitization is emphasized in discussion

Testing the theory of immune selection in cancers that break the rules of transplantation

Abstract Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Diabetes and disordered eating behaviours in a community-based sample of australian adolescents

Background:People with diabetes have been shown to be at risk for disordered eating compared to their non-diabetic peers. However, the majority of studies have been conducted in relatively small samples drawn from clinical diabetes settings or registries. Community-based samples are required to better understand disordered eating behaviours in this population. In a large community-based population sample of Australian adolescents, this study aimed to (1) investigate disordered eating behaviours in adolescents reporting a diagnosis of diabetes compared to their non-diabetic peers and (2) test associations between disordered eating behaviours and insulin restriction.Methods:Secondary school students (n = 4854; mean (SD) age 14.4 (1.6) years; 47% boys) completed an online survey, including self-reported presence of diabetes, demographics, weight status, substance use, insulin restriction and disordered eating behaviours. Clinically meaningful cut-offs for disordered eating behaviours were generated for analysis.Results:Disordered eating behaviours, specifically self-induced vomiting (diabetes 19.2%, no diabetes 3.3%; p p p p Conclusion:There was a high rate of disordered eating behaviours in adolescents with diabetes compared to their peers without diabetes. The findings of this study may have the potential to inform future health promotion, prevention, and early intervention approaches for those with comorbid diabetes and disordered eating behaviours. Future longitudinal studies are required to evaluate disordered eating behaviours in those with diabetes over time in community-based samples

Modeling oscillatory Microtubule--Polymerization

Polymerization of microtubules is ubiquitous in biological cells and under certain conditions it becomes oscillatory in time. Here simple reaction models are analyzed that capture such oscillations as well as the length distribution of microtubules. We assume reaction conditions that are stationary over many oscillation periods, and it is a Hopf bifurcation that leads to a persistent oscillatory microtubule polymerization in these models. Analytical expressions are derived for the threshold of the bifurcation and the oscillation frequency in terms of reaction rates as well as typical trends of their parameter dependence are presented. Both, a catastrophe rate that depends on the density of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay reaction, such as the depolymerization of shrinking microtubules or the decay of oligomers, support oscillations. For a tubulin dimer concentration below the threshold oscillatory microtubule polymerization occurs transiently on the route to a stationary state, as shown by numerical solutions of the model equations. Close to threshold a so--called amplitude equation is derived and it is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure

The UKIDSS Galactic Plane Survey

'The definitive version is available at www.blackwell-synergy.com .' Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.13924.xThe UKIDSS Galactic Plane Survey (GPS) is one of the five near-infrared Public Legacy Surveys that are being undertaken by the UKIDSS consortium, using the Wide Field Camera on the United Kingdom Infrared TelescopePeer reviewe

Burden and health-related quality of life of eating disorders, including Avoidant/Restrictive Food Intake Disorder (ARFID), in the Australian population

Background: Little is known about the epidemiology and health related quality of life (HRQoL) of the new DSM-5 diagnoses, Binge Eating Disorder (BED) and Avoidant/Restrictive Food Intake Disorder (ARFID) in the Australian population. We aimed to investigate the prevalance and burden of these disorders. Methods: We conducted two sequential population-based surveys including individuals aged over 15 years who were interviewed in 2014 (n = 2732) and 2015 (n =3005). Demographic information and diagnostic features of DSM-5 eating disorders were asked including the occurrence of regular (at least weekly over the past 3 months) objective binge eating with levels of distress, extreme dietary restriction/fasting for weight/shape control, purging behaviors, overvaluation of shape and/or weight, and the presence of an avoidant/restrictive food intake without overvaluation of shape and/or weight. In 2014 functional impact or role performance was measured with the 'days out of role' question and in 2015, Health Related Quality of Life (HRQoL) was assessed with the Short Form -12 item questionnaire (SF-12v1). Results: The 2014 and 2015 3-month prevalence of eating disorders were: anorexia nervosa-broad 0.4% (95% CI 0.2-0.7) and 0.5% (0.3-0.9); bulimia nervosa 1.1% (0.7-1.5) and 1.2% (0.9-1.7); ARFID 0.3% (0.1-0.5) and 0.3% (0.2-0.6). The 2015 3-month prevalence rates were: BED-broad 1.5% (1.1-2.0); Other Specified Feeding or Eating Disorder (OSFED) 3.2 (2.6-3.9); and Unspecified Feeding or Eating Disorder (UFED) 10.4% (0.9-11.5). Most people with OSFED had atypical anorexia nervosa and majority with UFED were characterised by having recurrent binge eating without marked distress. Eating disorders were represented throughout sociodemographic groups and those with bulimia nervosa and BED-broad had mean weight (BMI, kg/m²) in the obese range. Mental HRQoL was poor in all eating disorder groups but particularly poor for those with BED-broad and ARFID. Individuals with bulimia nervosa, BED-broad and OSFED-Purging Disorder also had poor physical HRQoL. ARFID and bulimia nervosa groups had lower role performance than those without an eating disorder. Conclusions: Whilst full spectrum eating disorders, including ARFID, were less common than OSFED or UFED, they were associated with poor mental HRQoL and significant functional impairment. The present study supports the movement of eating disorders in to broader socio demographic groups including men, socio-economic disadvantaged groups and those with obesity.Phillipa Hay, Deborah Mitchison, Abraham Ernesto Lopez Collado, David Alejandro González-Chica, Nigel Stocks and Stephen Touy

Ectopic A-lattice seams destabilize microtubules

Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe