Adaptation in the chemotactic guidance of nerve growth cones

Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.     

Fisheries productivity in the northeastern Pacific Ocean over the past 2,200 years

Historical catch records suggest that climatic variability has had basin-wide effects on the northern Pacific and its fish populations, such as salmon, sardines and anchovies. However, these records are too short to define the nature and frequency of patterns. We reconstructed approximately 2,200-year records of sockeye salmon abundance from sediment cores obtained from salmon nursery lakes on Kodiak island, Alaska. Large shifts in abundance, which far exceed the decadal-scale variability recorded during the past 300 years, occurred over the past two millennia. A marked, multi-centennial decline in Alaskan sockeye salmon was apparent from approximately 100 BC to AD 800, but salmon were consistently more abundant from AD 1200 to 1900. Over the past two millennia, the abundances of Pacific sardine and Northern anchovy off the California coast, and of Alaskan salmon, show several synchronous patterns of variability. But sardines and anchovies vary out of phase with Alaskan salmon over low frequency, which differs from the pattern detected in historical records. The coherent patterns observed across large regions demonstrate the strong role of climatic forcing in regulating northeastern Pacific fish stocks.     

Antarctic climate cooling and terrestrial ecosystem response.

The average air temperature at the Earth's surface has increased by 0.06 degrees C per decade during the 20th century, and by 0.19 degrees C per decade from 1979 to 1998. Climate models generally predict amplified warming in polar regions, as observed in Antarctica's peninsula region over the second half of the 20th century. Although previous reports suggest slight recent continental warming, our spatial analysis of Antarctic meteorological data demonstrates a net cooling on the Antarctic continent between 1966 and 2000, particularly during summer and autumn. The McMurdo Dry Valleys have cooled by 0.7 degrees C per decade between 1986 and 2000, with similar pronounced seasonal trends. Summer cooling is particularly important to Antarctic terrestrial ecosystems that are poised at the interface of ice and water. Here we present data from the dry valleys representing evidence of rapid terrestrial ecosystem response to climate cooling in Antarctica, including decreased primary productivity of lakes (6-9% per year) and declining numbers of soil invertebrates (more than 10% per year). Continental Antarctic cooling, especially the seasonality of cooling, poses challenges to models of climate and ecosystem change.     

Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice

Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.     

Damage to the shallow Landers fault from the nearby Hector Mine earthquake

Crustal faults have long been identified as sites where localized sliding motion occurs during earthquakes, which allows for the relative motion between adjacent crustal blocks. Although there is a growing awareness that we must understand the evolution of fault systems on many timescales to relate present-day crustal stresses and fault motions to geological structures formed in the past, fault-zone damage and healing have been documented quantitatively in only a few cases. We have been monitoring the healing of damage on the shallow Johnson Valley fault after its rupture in the 1992 magnitude-7.3 Landers earthquake, and here we report that this healing was interrupted in 1999 by the magnitude-7.1 Hector Mine earthquake rupture, which occurred 20-30 km away. The Hector Mine earthquake both strongly shook and permanently strained the Johnson Valley fault, adding damage discernible as a temporary reversal of the healing process. The fault has since resumed the trend of strength recovery that it showed after the Landers earthquake. These observations lead us to speculate that fault damage caused by strong seismic waves may help to explain earthquake clustering and seismicity triggering by shaking, and may be involved in friction reduction during faulting.     

Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype

The immune system must distinguish not only between self and non-self, but also between innocuous and pathological foreign antigens to prevent unnecessary or self-destructive immune responses. Unresponsiveness to harmless antigens is established through central and peripheral processes. Whereas clonal deletion and anergy are mechanisms of peripheral tolerance, active suppression by T-regulatory 1 (Tr1) cells has emerged as an essential factor in the control of autoreactive cells. Tr1 cells are CD4+ T lymphocytes that are defined by their production of interleukin 10 (IL-10) and suppression of T-helper cells; however, the physiological conditions underlying Tr1 differentiation are unknown. Here we show that co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4+ T cells. These CD3/CD46-stimulated IL-10-producing CD4+ cells proliferate strongly, suppress activation of bystander T cells and acquire a memory phenotype. Our findings identify an endogenous receptor-mediated event that drives Tr1 differentiation and suggest that the complement system has a previously unappreciated role in T-cell-mediated immunity and tolerance.