MHC class I–specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice

In a manner partially independent of activating Fcγ receptors, antibody-mediated production of complement component C5a and recruitment of macrophages elicit transfusion-related acute lung injury in mice

Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β

Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation

Differential effects of nicotine on alcohol consumption in men and women

Nicotine and alcohol are frequently co-used, suggesting that use of one drug may facilitate use of the other. Furthermore, because men and women differ in their responses to both drugs, it is possible that men and women also differ in their responses to the combination of nicotine and alcohol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46375/1/213_2006_Article_338.pd

Wavelength-dependent fluorescent immunosensors via incorporation of polarity indicators near the binding interface of antibody fragments

Herein, we describe a fluorescent immunosensor designed by incorporating an unnatural amino acid fluorophore into the binding site of an EGFR-specific antibody fragment, resulting in quantifiable EGFR-dependent changes in peak fluorescence emission wavelength. To date, immunosensor design strategies have relied on binding-induced changes in fluorescence intensity that are prone to excitation source fluctuations and sample-dependent noise. In this study, we used a rational design approach to incorporate a polarity indicator (Anap) into specific positions of an anti-EGFR single chain antibody to generate an emission wavelength-dependent immunosensor. We found that when incorporated within the topological neighborhood of the antigen binding interface, the Anap emission wavelength is blue-shifted by EGFR-binding in a titratable manner, up to 20 nm, with nanomolar detection limits. This approach could be applicable to other antibody/antigen combinations for integration into a wide range of assay platforms (including homogeneous, solid-phase assay, or microfluidic assays) for one-step protein quantification

Facial motor nucleus AAV-Cre injection leads to MN-selective expression of Cre

Facial MNs immunohistochemically labeled for expression of either the MN marker, choline acetyltransferase (red in A) or the neuronal marker, NeuN (red in B), and Cre (green in both A and B; yellow where both signals are approximately balanced). The Cre is found in the MNs, consistent with the reporter data. Arrows designate MNs with higher levels of Cre immunoreactivity, while arrowheads designate MNs with lower levels. Scale bars: 10 μm (A); 15 μm (B).<p><b>Copyright information:</b></p><p>Taken from "Conditional, genetic disruption of ciliary neurotrophic factor receptors reveals a role in adult motor neuron survival"</p><p></p><p>The European Journal of Neuroscience 2008;27(11):2830-2837.</p><p>Published online Jan 2008</p><p>PMCID:PMC2431126.</p><p>© The Authors (2008). Journal compilation © 2008 Federation of European Neuroscience Societies and Blackwell Publishing Ltd</p