Investigation of pre-existing reactivity to biotherapeutics can uncover potential immunogenic epitopes and predict immunogenicity risk.
AuthorsBivi N, Moore T, Rodgers G, Denning H, Shockley T, Swearingen CA, Gelfanova V, Calderon B, Peterson DA, Hodsdon ME, Siegel RW, Higgs RE, Konrad RJ
JournalMAbs
PubMed ID31099718
'Despite recent advances in the development of tools to predict immunogenicity risk of biotherapeutic molecules, the ability of a protein to elicit the formation of anti-drug antibodies (ADA) remains one of the most common causes for termination of clinical development programs. In this study, we use ADA assays to detect ... More
Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance.
AuthorsWang Y, Cho C, Williams J, Smallwood PM, Zhang C, Junge HJ, Nathans J
JournalProc Natl Acad Sci U S A
PubMed ID30478038
'ß-Catenin signaling controls the development and maintenance of the blood-brain barrier (BBB) and the blood-retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand-receptor systems-the Norrin and Wnt7a/Wnt7b systems-are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB ... More
Beneficial Role of Rosuvastatin in Blood-Brain Barrier Damage Following Experimental Ischemic Stroke.
'Hemorrhage transformation is the most challenging preventable complication in thrombolytic therapy and is related to recombinant tissue plasminogen activator (rt-PA)-induced blood-brain barrier (BBB) damage. Intraperitoneal injections of normal or high doses of rosuvastatin were administered to Balb/c mice 20 min prior to middle cerebral artery occlusion (MCAO) surgery for 3 ... More
Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells.
AuthorsAdkins I, Sadilkova L, Hradilova N, Tomala J, Kovar M, Spisek R
JournalOncoimmunology
PubMed ID28638734
The mechanisms of immunogenicity underlying mild heat-shock (mHS) treatment < 42°C of tumor cells are largely attributed to the action of heat-shock proteins; however, little is known about the immunogenicity of tumor cells undergoing severe cytotoxic heat-shock treatment (sHS > 43°C). Here, we found that sHS, but not mHS (42°C), ... More
Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.
AuthorsDionne G, Qiu X, Rapp M, Liang X, Zhao B, Peng G, Katsamba PS, Ahlsen G, Rubinstein R, Potter CS, Carragher B, Honig B, Müller U, Shapiro L
JournalNeuron
PubMed ID30057206
The tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric ... More
The Capsule of Cryptococcus neoformans Modulates Phagosomal pH through Its Acid-Base Properties.
AuthorsDe Leon-Rodriguez CM, Fu MS, Çorbali MO, Cordero RJB, Casadevall A
JournalmSphere
PubMed ID30355667
Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that ... More
Engineering of anti-human interleukin-4 receptor alpha antibodies with potent antagonistic activity.
AuthorsKim JE, Jung K, Kim JA, Kim SH, Park HS, Kim YS
JournalSci Rep
PubMed ID31123339
Development of antagonistic antibody (Ab) against interleukin-4 receptor alpha (IL-4Ra) subunit of IL-4/IL-13 receptors is a promising therapeutic strategy for T helper 2 (T
Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer's disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability ... More
Sex-regulated gene dosage effect of PPARa on synaptic plasticity.
AuthorsPierrot N, Ris L, Stancu IC, Doshina A, Ribeiro F, Tyteca D, Baugé E, Lalloyer F, Malong L, Schakman O, Leroy K, Kienlen-Campard P, Gailly P, Brion JP, Dewachter I, Staels B, Octave JN
JournalLife Sci Alliance
PubMed ID30894406
Mechanisms driving cognitive improvements following nuclear receptor activation are poorly understood. The peroxisome proliferator-activated nuclear receptor alpha (PPARa) forms heterodimers with the nuclear retinoid X receptor (RXR). We report that PPARa mediates the improvement of hippocampal synaptic plasticity upon RXR activation in a transgenic mouse model with cognitive deficits. This ... More
Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures.
AuthorsWang Y, Sabbagh MF, Gu X, Rattner A, Williams J, Nathans J
JournalElife
PubMed ID30932813
The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high ... More