Cognition and behaviour in children with congenital abdominal wall defects.

Aim: To characterise neurodevelopment at age two years and cognition and behaviour at age five years in children born with abdominal wall defects (gastroschisis or exomphalos).

Study Design: Participants were treated as neonates for gastroschisis or exomphalos and invited for routine clinical follow-up at ages two and five years. Thirty-nine two year-olds and 20 five year-olds with gastroschisis and 20 two year-olds and 10 five year-olds with exomphalos returned for age-appropriate assessments of development (two years) and intellectual functioning (IQ), executive function, and behavioural problems.

Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) Subunit.

Building upon the success of bortezomib (VELCADE) and carfilzomib (KYPROLIS), the design of a next generation of inhibitors targeting specific subunits within the immunoproteasome is of interest for the treatment of autoimmune disease. There are three catalytic subunits within the immunoproteasome (low molecular mass polypeptide-7, -2, and multicatalytic endopeptidase complex subunit-1; LMP7, LMP2, and MECL-1), and a campaign was undertaken to design a potent and selective LMP2 inhibitor with sufficient properties to allow for sustained inhibition . Screening a focused library of epoxyketones revealed a series of potent dipeptides that were optimized to provide the highly selective inhibitor ().

Assessment of Blood Collection from the Lateral Saphenous Vein for Microfilaria Counts in Mongolian Gerbils (Meriones unguiculatus) Infected with Brugia pahangi.

The NIH guidelines for survival bleeding of mice and rats note that using the retroorbital plexus has a greater potential for complications than do other methods of blood collection and that this procedure should be performed on anesthetized animals. Lateral saphenous vein puncture has a low potential for complications and can be performed without anesthesia. Mongolian gerbils (Meriones unguiculatus) are the preferred rodent model for filarial parasite research.

Endotracheal intubation and oral gavage in the domestic chicken.

The domestic chicken (Gallus gallus) is increasing in popularity as a laboratory animal, as it is useful in multiple fields of biomedical research and has the practical benefits of being relatively inexpensive, easy to handle and able to adapt to various settings. Here, we describe two procedures commonly used with chickens in research: endotracheal intubation and oral gavage.

Techniques for collecting blood from the domestic chicken.

As the use of chickens in biomedical research is increasing, demand is growing for technical skills involving poultry, particularly techniques such as venipuncture. Phlebotomy (blood collection) is an important diagnostic tool for determining causes of morbidity and mortality and for collection of other research-relevant data. This column describes four standard methods of blood collection from the domestic chicken.

Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses.

7α,25-dihydroxycholesterol (7α,25-OHC) is a ligand for the G protein-coupled receptor EBI2; however, the cellular sources of this oxysterol are undefined. 7α,25-OHC is synthesized from cholesterol by the stepwise actions of two enzymes, CH25H and CYP7B1, and is metabolized to a 3-oxo derivative by HSD3B7. We showed that all three enzymes control EBI2 ligand concentration in lymphoid tissues.

Unassisted blood collection from unanesthetized rats and gerbils.

Blood collection is a common procedure in animal research. This column describes humane methods of collecting blood from the rat and the gerbil that can be carried out by a single person on an awake animal.

Transtracheal aspiration and infusion in the horse.

Transtracheal access enables researchers to obtain diagnostic samples from or infuse materials into the lower respiratory tract. This column describes transtracheal aspiration and infusion of horses.

EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues.

EBV-induced gene 2 (EBI2) was recently shown to direct the delayed movement of activated B cells to interfollicular and outer follicular regions of secondary lymphoid organs and to be required for mounting a normal T-dependent Ab response. In this study, we show that EBI2 promotes an early wave of Ag-activated B cell migration to the outer follicle in mice. Later, when B cells have moved to the T zone in a CCR7-dependent manner, EBI2 helps distribute the cells along the B zone-T zone boundary.

Oxysterols direct immune cell migration via EBI2.

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2.

Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses.

Humoral immune responses depend on B cells encountering antigen, interacting with helper T cells, proliferating and differentiating into low-affinity plasma cells or, after organizing into a germinal center (GC), high-affinity plasma cells and memory B cells. Remarkably, each of these events occurs in association with distinct stromal cells in separate subcompartments of the lymphoid tissue. B cells must migrate from niche to niche in a rapid and highly regulated manner to successfully mount a response.

EBI2 mediates B cell segregation between the outer and centre follicle.

B cell follicles are specialized microenvironments that support events necessary for humoral immunity. After antigen encounter, activated B cells initially seek T-cell help at the follicle-T-zone boundary and then move to interfollicular and T-zone distal (outer) regions of the follicle. Subsequently, some cells move to the follicle centre, become germinal centre B cells and undergo antibody affinity maturation.

Visualizing B cell capture of cognate antigen from follicular dendritic cells.

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs.

Recanalization of chronic total peripheral arterial occlusions using optical coherent reflectometry with guided radiofrequency energy: a single center experience.

Background: A forward-looking, fiberoptic guided device (Safe-Cross System, Intraluminal Therapeutics, Carlsbad, CA) has been used with guided radiofrequency energy to open chronic total occlusions (CTOs). This report describes the use of optical coherent reflectometry (OCR) system to assess safety and efficacy of opening CTOs in native peripheral arteries in the lower extremities: iliac, femoral, and popliteal.

Methods: 18 CTOs in native peripheral arteries in 17 patients were treated with OCR after failed attempts with conventional wires (minimum 10 min of fluoroscopic time).

Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell survival.

Chronic engagement of the B cell receptor by soluble autoantigen leads to reduced B cell survival. Using the Ig and hen egg lysozyme double transgenic mouse model, we demonstrate that the survival of soluble autoantigen-engaged B cells is further reduced in mice lacking CD4 T cells or deficient in CD40. Mixed bone marrow chimera experiments reveal that, under homeostatic conditions, the CD40L-CD40 pathway can augment autoreactive B cell survival in a non-cell-autonomous manner.

Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis.

Inflammation in the central nervous system (CNS) can be studied in experimental autoimmune encephalomyelitis (EAE). The proinflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) are implicated in EAE pathogenesis. Signals through the type 1 TNF receptor (TNFR1) are required for severe EAE to develop, whereas deficiency in IFN-gamma or its receptor result in more severe EAE.