Morphology, growth characteristics and oestrogen-binding capacity of DMBA-induced mammary tumours from ovariectomized rats.

The morphology of 20 mammary adenocarcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) in Sprague-Dawley rats was compared with their growth characteristics and oestrogen-binding capacity following ovariectomy. The capacity to bind (3H)oestradiol-17B did not appear to be related to the growth characteristics, time of appearance after DMBA administration, or time between ovariectomy and assay for specific oestrogen-binding proteins. Furthermore, different tumours appeared to have oestrogen-binding capacities unrelated to the percentage of neoplastic cells within the tumour, amount of inflammation, mast cell infiltration, or the presence of fluid-filled cysts. The only morphological features which appeared to be correlated with oestrogen-binding capacity were the number of mitoses and the lipid content of the tumour; that is, the oestrogen-binding capacity tended to be lower in tumours with moderate or large numbers of mitoses and in tumours with much lipid in the epithelial cells. Six of the 19 adenocarcinomas found prior to sacrifice either continued growing or remained static following ovariectomy, while the others underwent regression. In 5 of the regressing tumours a new growth phase was observed, usually beginning 2 months after ovariectomy. Tumours other thus osteosarcoma as well as fibroadenomas and Zymbal-gland tumours

Developing trauma-informed teacher education in England

Trauma-informed practice in education is an area of growing interest in England and internationally. Embracing trauma-informed practice in schools requires trauma and related content to be included in teacher education. Over a period of eight years, a short course was developed and incorporated into the teacher preparation programmes at a large university in England. Through methods of teacher educator self-study and autoethnography, we examine the process of the course’s development and identify mechanisms, enablers and barriers to change in the current policy context of teacher education in England. Important factors that supported change were the gradual development, external collaboration, positive outcomes as a warrant and source of motivation, the development of champions and enthusiasts for trauma-informed practice, and departmental leadership support. Barriers to the development were the constraints of prescribed content on initial teacher education courses, prevailing practices in some schools and settings, challenges in adapting material suitably for all education phases, and some beginning teachers’ responses to personally relevant course content. The successful introduction of the short course demonstrates that inclusion of trauma-informed content in initial teacher education is possible even in an unfavourable policy environment

The Scientific Study of Positive Psychology, Religion/Spirituality, and Physical Health

Humans have long been interested in relations among religion/spirituality (R/S), positive psychological constructs, and physical health. Furthermore, many religions attempt to influence behavior through health-related prescriptions about food choices, sexual activity, substance use, and resting. Similarly, positive psychological constructs have been discussed in light of their presumed benefits on both mental and physical health (Ryff & Singer, 1998). However, R/S and positive psychological constructs have only recently become objects of scientific investigation of their associations with physical health.https://digitalcommons.chapman.edu/psychology_books/1025/thumbnail.jp

Gravitational detection of a low-mass dark satellite at cosmological distance

The mass-function of dwarf satellite galaxies that are observed around Local Group galaxies substantially differs from simulations based on cold dark matter: the simulations predict many more dwarf galaxies than are seen. The Local Group, however, may be anomalous in this regard. A massive dark satellite in an early-type lens galaxy at z = 0.222 was recently found using a new method based on gravitational lensing, suggesting that the mass fraction contained in substructure could be higher than is predicted from simulations. The lack of very low mass detections, however, prohibited any constraint on their mass function. Here we report the presence of a 1.9 +/- 0.1 x 10^8 M_sun dark satellite in the Einstein-ring system JVAS B1938+666 at z = 0.881, where M_sun denotes solar mass. This satellite galaxy has a mass similar to the Sagittarius galaxy, which is a satellite of the Milky Way. We determine the logarithmic slope of the mass function for substructure beyond the local Universe to be alpha = 1.1^+0.6_-0.4, with an average mass-fraction of f = 3.3^+3.6_-1.8 %, by combining data on both of these recently discovered galaxies. Our results are consistent with the predictions from cold dark matter simulations at the 95 per cent confidence level, and therefore agree with the view that galaxies formed hierarchically in a Universe composed of cold dark matter.Comment: 25 pages, 7 figures, accepted for publication in Nature (19 January 2012

Conjugation site heterogeneity causes variable electrostatic properties in Fc conjugates

Immunoconjugates, including antibody-drug conjugates and Fc-conjugates, represent a rapidly growing class of therapeutics undergoing clinical development. Despite their growing popularity, the high intrinsic heterogeneity of immunoconjugates often complicates the development process and limits their widespread application. In particular, immunoconjugate charge variants exhibit markedly different colloidal stabilities, solubilities, pharmacokinetics and tissue distributions. Charge variants arise spontaneously due to degradation and, depending on the type of drug, linker and conjugation site, through drug conjugation. Electrostatic changes in naked antibodies often result in poor performance characteristics, and therefore charge alterations due to degradation are critical to control. Charge properties are expected to be equally important to producing well-behaved ADCs. Charge-based methods of analysis, such as isoelectric focusing and ion exchange chromatography, are capable of probing the underlying complexities within immunoconjugate drug products. Despite the utility of these methods, there are only a few published reports of charge-based assays applied to immunoconjugates. In the present study, we sought to identify the effects of chemical conjugation on the electrostatic properties of Fc-conjugates. In order to minimize the effects of post-translational modifications (e.g. deamidation), a single Fc charge variant was isolated prior to conjugation of a fluorescent probe, Alexa Fluor 350, to the side chains of lysine residues. The resulting Fc-conjugates were assessed by a variety of analytical techniques, including isoelectric focusing and ion exchange chromatography, to determine their charge properties

Characterization of the anti‐factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence‐based immunoassay

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110532/1/jth12768.pd

Motility Screen Identifies Drosophila IGF-II mRNA-Binding Protein—Zipcode-Binding Protein Acting in Oogenesis and Synaptogenesis

The localization of specific mRNAs can establish local protein gradients that generate and control the development of cellular asymmetries. While all evidence underscores the importance of the cytoskeleton in the transport and localization of RNAs, we have limited knowledge of how these events are regulated. Using a visual screen for motile proteins in a collection of GFP protein trap lines, we identified the Drosophila IGF-II mRNA-binding protein (Imp), an ortholog of Xenopus Vg1 RNA binding protein and chicken zipcode-binding protein. In Drosophila, Imp is part of a large, RNase-sensitive complex that is enriched in two polarized cell types, the developing oocyte and the neuron. Using time-lapse confocal microscopy, we establish that both dynein and kinesin contribute to the transport of GFP-Imp particles, and that regulation of transport in egg chambers appears to differ from that in neurons. In Drosophila, loss-of-function Imp mutations are zygotic lethal, and mutants die late as pharate adults. Imp has a function in Drosophila oogenesis that is not essential, as well as functions that are essential during embryogenesis and later development. Germline clones of Imp mutations do not block maternal mRNA localization or oocyte development, but overexpression of a specific Imp isoform disrupts dorsal/ventral polarity. We report here that loss-of-function Imp mutations, as well as Imp overexpression, can alter synaptic terminal growth. Our data show that Imp is transported to the neuromuscular junction, where it may modulate the translation of mRNA targets. In oocytes, where Imp function is not essential, we implicate a specific Imp domain in the establishment of dorsoventral polarity

Mergers and Mass Accretion Rates in Galaxy Assembly: The Millennium Simulation Compared to Observations of z~2 Galaxies

Recent observations of UV-/optically selected, massive star forming galaxies at z~2 indicate that the baryonic mass assembly and star formation history is dominated by continuous rapid accretion of gas and internal secular evolution, rather than by major mergers. We use the Millennium Simulation to build new halo merger trees, and extract halo merger fractions and mass accretion rates. We find that even for halos not undergoing major mergers the mass accretion rates are plausibly sufficient to account for the high star formation rates observed in z~2 disks. On the other hand, the fraction of major mergers in the Millennium Simulation is sufficient to account for the number counts of submillimeter galaxies (SMGs), in support of observational evidence that these are major mergers. When following the fate of these two populations in the Millennium Simulation to z=0, we find that subsequent mergers are not frequent enough to convert all z~2 turbulent disks into elliptical galaxies at z=0. Similarly, mergers cannot transform the compact SMGs/red sequence galaxies at z~2 into observed massive cluster ellipticals at z=0. We argue therefore, that secular and internal evolution must play an important role in the evolution of a significant fraction of z~2 UV-/optically and submillimeter selected galaxy populations.Comment: 5 pages, 4 figures, Accepted for publication in Ap