Analysis of primary cilia in the developing mouse brain.

Stem and progenitor cells in the developing mammalian brain are highly polarized cells that carry a primary cilium protruding into the brain ventricles. Here, cilia detect signals present in the cerebrospinal fluid that fills the ventricles. Recently, striking observations have been made regarding the dynamics of primary cilia in mitosis and cilium reformation after cell division.

Neurogenesis during development of the vertebrate central nervous system.

During vertebrate development, a wide variety of cell types and tissues emerge from a single fertilized oocyte. One of these tissues, the central nervous system, contains many types of neurons and glial cells that were born during the period of embryonic and post-natal neuro- and gliogenesis. As to neurogenesis, neural progenitors initially divide symmetrically to expand their pool and switch to asymmetric neurogenic divisions at the onset of neurogenesis.

A comparative study of nucleostemin family members in zebrafish reveals specific roles in ribosome biogenesis.

Nucleostemin (NS) is an essential protein for the growth and viability of developmental stem cells. Its functions are multi-faceted, including important roles in ribosome biogenesis and in the p53-induced apoptosis pathway. While NS has been well studied, the functions of its family members GNL2 and GNL3-like (GNL3L) remain relatively obscure despite a high degree of sequence and domain homology.

Asymmetric inheritance of centrosome-associated primary cilium membrane directs ciliogenesis after cell division.

Primary cilia are key sensory organelles that are thought to be disassembled prior to mitosis. Inheritance of the mother centriole, which nucleates the primary cilium, in relation to asymmetric daughter cell behavior has previously been studied. However, the fate of the ciliary membrane upon cell division is unknown.

Basolateral rather than apical primary cilia on neuroepithelial cells committed to delamination.

Delamination of neural progenitors from the apical adherens junction belt of the neuroepithelium is a hallmark of cerebral cortex development and evolution. Specific cell biological processes preceding this delamination are largely unknown. Here, we identify a novel, pre-delamination state of neuroepithelial cells in mouse embryonic neocortex.

The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish.

Nucleostemin (NS), a member of a family of nucleolar GTP-binding proteins, is highly expressed in proliferating cells such as stem and cancer cells and is involved in the control of cell cycle progression. Both depletion and overexpression of NS result in stabilization of the tumor suppressor p53 protein in vitro. Although it has been previously suggested that NS has p53-independent functions, these to date remain unknown.

Apc1 is required for maintenance of local brain organizers and dorsal midbrain survival.

The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin pathway, which is vital for induction and patterning of the early vertebrate brain. However, its role in later brain development is less clear. Here, we examined the mechanisms underlying effects of an Apc1 zygotic-effect mutation on late brain development in zebrafish.

Apc1-mediated antagonism of Wnt/beta-catenin signaling is required for retino-tectal pathfinding in the zebrafish.

The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin pathway. We examined the effects of an Apc1 loss-of-function mutation on retino-tectal axon pathfinding in zebrafish. In apc mutants, the retina is disorganized and optic nerves portray pathfinding defects at the optic chiasm and do not project properly to the tectum.

The innate immune response to adjuvants dictates the adaptive immune response to autoantigens.

To elucidate the role of innate immunity in susceptibility to the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunization with spinal cord homogenate (SCH) plus complete Freund adjuvant or carbonyl iron in 3 inbred rat strains. Lewis are considered "susceptible," PVG/c-Rt7a (PVG) as "semisusceptible," and Brown Norway (BN) as "resistant" to EAE. Immunization with SCH-carbonyl iron resulted in clinical disease in all 3 strains, but the pathologic features of EAE in the resistant BN and the semisusceptible PVG rats differed from those in the Lewis and PVG model of EAE induced with SCH-complete Freund adjuvant.

Nitric oxide contributes to resistance of the Brown Norway rat to experimental autoimmune encephalomyelitis.

The Brown Norway (BN) rat is reported to be resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and a number of mechanisms have been suggested to explain this resistance. In work reported here we provide evidence that such resistance in the BN rat can be accounted for, at least in part, by their ability to produce higher levels of nitric oxide (NO) than susceptible strains of rats. Spleen cells from the BN rat make significantly more NO following in vitro stimulation than do cells from the Lewis or PVG rat and following in vivo immunization using complete Freund's adjuvant (CFA) the BN rat makes substantially more NO than either susceptible strain.

Anti-HIV drug development--an overview.

Highly active antiretroviral therapy (HAART) has markedly decreased mortality and morbidity in the developed world. HAART consists of a combination of three or more of the following classes of antiretroviral (ARV) drug: reverse transcriptase inhibitors, protease inhibitors and a recently approved fusion inhibitor. However, HAART cannot completely eradicate HIV from the body, results in long-term toxicity and eventually leads to the emergence of drug-resistant HIV strains.

Aspirin-like molecules that inhibit human immunodeficiency virus 1 replication.

Some anti-inflammatory molecules are also known to possess anti-human immunodeficiency virus (HIV) activity. We found that o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS), a recently synthesized non-steroidal anti-inflammatory molecule can inhibit HIV-1 replication. The aim of this study was to clarify the mechanism of action of APHS.

APHS can act synergically with clinically available HIV-1 reverse transcriptase and protease inhibitors and is active against several drug-resistant HIV-1 strains in vitro.

Objectives: The use of multiple drug combinations in current anti-human immunodeficiency virus (HIV) therapy allows lower dosages of individual drugs and results in enhancement of the therapeutic effect due to synergic interactions between different drugs. We have shown that o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS), a recently developed non-steroidal anti-inflammatory drug, shows anti-HIV activity in a dose-dependent manner. The first aim of this study was to investigate whether APHS can act synergically with the clinically available reverse transcriptase and protease inhibitors (RTIs and PIs, respectively) in vitro.