LIM kinase 1, a key regulator of actin dynamics, is widely expressed in embryonic and adult tissues.

The expression of endogenous LIM kinase 1 (LIMK1) protein was investigated in embryonic and adult mice using a rat monoclonal antibody (mAb), which recognizes specifically the PDZ domain of LIMK1 and not LIMK2. Immunoblotting analysis revealed widespread expression of LIMK1 existing as a 70-kDa protein in tissues and in cell lines, with a higher mass form (approximately 75 kDa) present in some tissues and cell lines. Smaller isoforms of approximately 50 kDa were also occasionally evident.

(Pro)insulin-specific regulatory T cells.

Regulatory anti-diabetogenic T cells (T(reg)) can be induced by the mucosal administration of insulin or proinsulin peptides, in the non-obese diabetic (NOD) mouse model of autoimmune type 1 diabetes. Naso-respirtory insulin (which avoids insulin degradation) induces CD8+ alpha(alpha) TCR gamma(delta) T(reg) whereas peptides that bind to the NOD MHC class II molecule, I-Ag7, insulin B9-23 and proinsulin B24-C36, induce CD4+ T(regs) Following naso-respiratory delivery of insulin to NOD mice increased numbers of CD8+ gamma(delta) T cells expressing interleukin (IL)10 are detected in the pancreatic lymph nodes. Neonatal (3 day) thymectomy (NTX) dramatically accelerates diabetes development in NOD mice, associated with lymphopaenia and a block in the maturation of mucosal intrepithelial lymphocytes (IEL), especially extrathymic-derived CD8+ alpha(alpha) TCR gamma(delta) IEL.

Conservation of L and 3C proteinase activities across distantly related aphthoviruses.

The foot-and-mouth disease virus (FMDV) leader (L) proteinase is an important virulence determinant in FMDV infections. It possesses two distinct catalytic activities: (i) C-terminal processing at the L/VP4 junction; and (ii) induction of the cleavage of translation initiation factor eIF4G, an event that inhibits cap-dependent translation in infected cells. The only other member of the Aphthovirus genus, equine rhinitis A virus (ERAV), also encodes an L protein, but this shares only 32% amino acid identity with its FMDV counterpart.

Anti-CD45RB antibody deters xenograft rejection by modulating T cell priming and homing.

Pancreatic islet xenotransplantation has been advocated as a way of overcoming the shortage of human donor tissue for the treatment of type 1 diabetes. However, the potent immune response against xenografts is a major barrier to their use. We show that a short course of the anti-CD45RB antibody, MB23G2, prolongs survival of fetal pig pancreas grafts in mice.

Bone morphogenetic proteins promote development of fetal pancreas epithelial colonies containing insulin-positive cells.

Extracellular signals that guide pancreas cell development are not well characterized. In an in vitro culture system of dissociated pancreas cells from the E15.5 mouse fetus we show that, in the presence of the extracellular matrix protein laminin-1, bone morphogenetic proteins (BMPs-4, -5 and -6) promote the development of cystic epithelial colonies.

The novel picornavirus Equine rhinitis B virus contains a strong type II internal ribosomal entry site which functions similarly to that of Encephalomyocarditis virus.

Equine rhinitis B virus (ERBV) has recently been classified as an Erbovirus, a new genus in the Picornaviridae family. ERBV is distantly related to members of the Cardiovirus and Aphthovirus genera which utilize a type II internal ribosome entry sequence (IRES) to initiate translation. We show that ERBV also possesses the core stem-loop structures (H-L) of a type II IRES.

Precursor cells in the subventricular zone of the adult mouse are actively inhibited from differentiating into neurons.

The adult mouse subventricular zone (SVZ) contains precursor cells capable of generating new neurons which populate the olfactory bulb. The SVZ precursors, however, appear to be restricted in their capacity to generate neurons in other regions of the brain indicating a tight regulation of their differentiation. We demonstrate in vitro that explants of SVZ are unable to generate neurons from dividing precursors, even though precursors are present and dividing within explant cultures.

Signaling of neuronal cell death by the p75NTR neurotrophin receptor.

The neurotrophin receptor (p75NTR) is best known for mediating tropic support by participating in the formation of high-affinity nerve growth factor (NGF) receptor complexes with trkA, however, p75NTR more recently has been shown to act as a bona fide death-signaling receptor, which can signal independently of trkA. This article discusses the evidence for an active role of p75NTR in neuronal cell death and the mechanisms controlling this process, including roles for Bcl-2 family members, the c-jun stress kinase JNK, the transcription factor nuclear factor kappa B (NFkappaB), and caspases.

Help for cytotoxic-T-cell responses is mediated by CD40 signalling.

Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effectors can act alone when killing target cells, their differentiation from naive CD8-positive T cells is often dependent on 'help' from CD4-positive helper T (TH) cells.