J. Lang | University of California, Davis (original) (raw)

Papers by J. Lang

Glia, 2015

The straightforward concept that accentuated Wnt signaling via the Wnt-receptor-β-catenin-TCF/LEF... more The straightforward concept that accentuated Wnt signaling via the Wnt-receptor-β-catenin-TCF/LEF cascade (also termed canonical Wnt signaling or Wnt/β-catenin signaling) delays or blocks oligodendrocyte differentiation is very appealing. According to this concept, canonical Wnt signaling is responsible for remyelination failure in multiple sclerosis and for persistent hypomyelination in periventricular leukomalacia. This has given rise to the hope that pharmacologically inhibiting this signaling will be of therapeutic potential in these disabling neurological disorders. But current studies suggest that Wnt/β-catenin signaling plays distinct roles in oligodendrogenesis, oligodendrocyte differentiation, and myelination in a context-dependent manner (central nervous system regions, developmental stages), and that Wnt/β-catenin signaling interplays with, and is subjected to regulation by, other central nervous system factors and signaling pathways. On this basis, we propose the more nuanced concept that endogenous Wnt/β-catenin activity is delicately and temporally regulated to ensure the seamless development of oligodendroglial lineage cells in different contexts. In this review, we discuss the role Wnt/β-catenin signaling in oligodendrocyte development, focusing on the interpretation of disparate results, and highlighting areas where important questions remain to be answered about oligodendroglial lineage Wnt/β-catenin signaling. GLIA 2015.

Vaccine, Jan 12, 2007

We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between ... more We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between 1990 and 2002 and prepared from the same seed lot that has been in continuous use since 1990. All vaccine batches displayed identical genome sequence. Only four nucleotide substitutions were observed, compared to previously published sequence, with no incidence at amino-acid level. Fine analysis of viral plaque size distribution was used as an additional marker for genetic stability and demonstrated a remarkable homogeneity of the viral population. The total virus load, measured by qRT-PCR, was also homogeneous pointing out reproducibility of the vaccine production process. Mice inoculated intracerebrally with the different bulks exhibited a similar average survival time, and ratio between in vitro potency and mouse LD(50) titers remained constant from batch-to-batch. Taken together, these data demonstrate the genetic stability of the strain at mass production level over a period of 12 y...

Veterinary Radiology & Ultrasound, 2004

The geometry of the lumbosacral region has been suspected to play a role in the development of de... more The geometry of the lumbosacral region has been suspected to play a role in the development of degenerative lumbosacral stenosis in the dog. In this study, 50 dogs (21 German Shepherd dogs and 29 dogs of other breeds) with clinical signs of cauda equina compression were studied by magnetic resonance (MR) imaging. The orientation of the articular process joints in the L5-S1 region and the angle difference between two adjacent motion segments were calculated. Intervertebral disc degeneration of the same region was identified and classified in four stages. A positive association between MR-imaging stage and articular process joint angle difference in the transverse plane was found in the two groups of animals. German Shepherd dogs and dogs of other breeds had different geometry of the lumbosacral region with different articular process joint angles in the transverse plane and statistically different stages of disc degeneration.

Mathematische Nachrichten, 2006

Let I = [a, b] ⊂ R, let 1 < q ≤ p < ∞, let u and v be positive functions with u ∈ L p (I) and v ∈... more Let I = [a, b] ⊂ R, let 1 < q ≤ p < ∞, let u and v be positive functions with u ∈ L p (I) and v ∈ Lq(I), and let T : Lp(I) → Lq(I) be the Hardy-type operator given by

Journal of Virology, 2004

Virology 298: [146][147][148][149][150][151][152][153][154][155][156][157][158][159] 2002). Proge... more Virology 298: [146][147][148][149][150][151][152][153][154][155][156][157][158][159] 2002). Progeny viruses were subjected to three rounds of plaque purifications to produce the Pre-Master Seed viruses at passage 7 (P7). Three further passages were carried out using U.S. current Good Manufacturing Practices (cGMP) to produce the Vaccine Lot (P10) viruses. Preclinical studies demonstrated that the vaccine candidates are replication competent and genetically stable and do not become more neurovirulent upon 20 passages in Vero cells. The safety of a tetravalent vaccine was determined and compared to that of YF-VAX in a formal monkey neurovirulence test. Brain lesions produced by the tetravalent ChimeriVax-DEN vaccine were significantly less severe than those observed with YF-VAX. The immunogenicity and protective efficacy of four different tetravalent formulations were evaluated in cynomolgus monkeys following a single-dose subcutaneous vaccination followed by a virulent virus challenge 6 months later. All monkeys developed low levels of viremia postimmunization, and all the monkeys that had received equal concentrations of either a high-dose (5,5,5,5) or a low-dose (3,3,3,3) formulation seroconverted against all four DEN virus serotypes. Twenty-two (92%) of 24 monkeys were protected as determined by lack of viremia post-challenge. This report is the first to demonstrate the safety of a recombinant DEN virus tetravalent vaccine in a formal neurovirulence test, as well as its protective efficacy in a monkey challenge model.