Multiple driving factors explain spatial and temporal variability in coral calcification rates on the Bermuda platform

Experimental studies have shown that coral calcification rates are dependent on light, nutrients, food availability, temperature, and seawater aragonite saturation (Ω _arag), but the relative importance of each parameter in natural settings remains uncertain. In this study, we applied Calcein fluorescent dyes as time indicators within the skeleton of coral colonies (n = 3) of Porites astreoides and Diploria strigosa at three study sites distributed across the northern Bermuda coral reef platform. We evaluated the correlation between seasonal average growth rates based on coral density and extension rates with average temperature, light, and seawater Ω _arag in an effort to decipher the relative importance of each parameter. The results show significant seasonal differences among coral calcification rates ranging from summer maximums of 243 ± 58 and 274 ± 57 mmol CaCO₃ m^?2 d^?1 to winter minimums of 135 ± 39 and 101 ± 34 mmol CaCO₃ m^?2 d^?1 for P. astreoides and D. strigosa, respectively. We also placed small coral colonies (n = 10) in transparent chambers and measured the instantaneous rate of calcification under light and dark treatments at the same study sites. The results showed that the skeletal growth of D. strigosa and P. astreoides, whether hourly or seasonal, was highly sensitive to Ω _arag. We believe this high sensitivity, however, is misleading, due to covariance between light and Ω _arag, with the former being the strongest driver of calcification variability. For the seasonal data, we assessed the impact that the observed seasonal differences in temperature (4.0 °C), light (5.1 mol photons m^?2 d^?1), and Ω _arag (0.16 units) would have on coral growth rates based on established relationships derived from laboratory studies and found that they could account for approximately 44, 52, and 5 %, respectively, of the observed seasonal change of 81 ± 14 mmol CaCO₃ m^?2 d^?1. Using short-term light and dark incubations, we show how the covariance of light and Ω _arag can lead to the false conclusion that calcification is more sensitive to Ω _arag than it really is.     

E3 ubiquitin ligase Cbl-b in innate and adaptive immunity

Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates innate immune responses and plays an important role in host defense to pathogens. Understanding the signaling pathways regulated by Cbl-b in innate and adaptive immune cells is therefore essential for efficient manipulation of Cbl-b in emerging immunotherapies for human disorders such as autoimmune diseases, allergic inflammation, infections, and cancer. In this article, we review the latest developments in the molecular structural basis of Cbl-b function, the regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune cells, as well as the biological function of Cbl-b in physiological and pathological immune responses in animal models and human diseases.     

Posttetanic potentiation and presynaptically induced long-term potentiation at the mossy fiber synapse in rat hippocampus

A form of long-term potentiation (LTP) is induced at the mossy fiber (MF) synapse in the hippocampus by highfrequency presynaptic stimulation (HFS). It is generally accepted that induction of this form of LTP (MF LTP) does not depend on postsynaptic Ca²⁺ current gated by N-methyl-D -aspartate receptors, but it has remained controversial whether induction depends on postsynaptic depolarization and voltage-gated entry of Ca²⁺. There are also contradictory data on the time course of both LTP and post-tetanic potentiation (PTP), a shorter duration form of potentiation observed at MF synapses immediately following HFS. It has been proposed that some of these differences in results may have arisen because of difficulties in isolating monosynaptic responses to MF input. In the present study, whole cell recording was used to observe excitatory postsynaptic currents (EPSCs) elicited in CA3 pyramidal cells by input from MFs. Postsynaptic cells were dialyzed with 1,2-bis(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA) and F^? to inhibit postsynaptic mechanisms that required Ca²⁺, cells were under voltage clamp during HFS, and conditions were selected to minimize the likelihood of polysynaptic contamination. Under these conditions, HFS nevertheless induced robust LTP (mean magnitude, 62%). The possibility that EPSCs were contaminated by polysynaptic components was investigated by exposing the slices to a suppressing medium (one that partially blocked neurotransmission). EPSC waveforms did not change shape during suppression, indicating that contamination was absent. The LTP observed always was accompanied by prominent PTP that lasted through the first 5 to 15 min following HFS (mean decay time constant, 3.2 min). Induction of this LTP was not cooperative; there was no relationship between the size of responses and the magnitude of the LTP induced. LTP magnitude also was unrelated to the extent to which postsynaptic cells depolarized during HFS. These results show that high rates of presynaptic MF activity elicit robust LTP whether or not there is accompanying postsynaptic depolarization or increase in the concentration of postsynaptic Ca²⁺. High-frequency MF activity also results in a PTP that is unusually large and long. © 1995 John Wiley & Sons, Inc.     

Mutational analysis of the C-terminal region of AREA,the transcription factor mediating nitrogen metabolite repression inAspergillus nidulans

InAspergillus nidulans the positive-acting, wide domain regulatory geneareA mediates nitrogen metabolite repression. Previous analysis demonstrated that the C-terminal 153 residues of theareA product (AREA) are inessential for at least partial expression of most genes subject to regulation byareA. Paradoxically,areA ^r 2, a ?1 frameshift replacing the wild-type 122 C-terminal residues with a mutant peptide of 117 amino acids, leads to general loss of function. To determine the basis for theareA ^r 2 mutant phenotype, and as a means of delineating functional domains within the C-terminal region of AREA, we have selected and characterisedareA ^r 2 revertants. Deletion analysis, utilising direct gene replacement, extended this analysis. A mutantareA product truncated immediately after the last residue of the highly conserved GATA (DNA-binding) domain retains partial function. TheareA ^r 2 product retains some function with respect to the expression ofuaZ (encoding urate oxidase) and the mutant allele is partially dominant with respect to nitrate reductase levels. Consistent with theareA ^r 2 product having a debilitating biological activity, we have demonstrated that a polypeptide containing both the wild-type DNA-binding domain and the mutant C-terminus of AREA2 is able to bind DNA in vitro but no longer shows specificity for GATA sequences.     

Analysis of neoplasms induced by Cas-Br-M MuLV tumor extracts

Cas-Br-M is an ecotropic murine leukemia virus isolated from wild mice that induces a wide spectrum of hematopoietic neoplasms, including T and B cell lymphomas, myelogenous leukemias, and erythroleukemias. The purpose of this study was to determine if the induction of neoplasms belonging to multiple lineages was due to the ecotropic virus itself or to the generation of cell lineage-specific recombinant viruses. The results demonstrate that in some instances (two of 12 tumor extracts tested), recombinant viruses can be recovered from primary Cas-Br-M-induced tumors that will induce lymphomas of single lineages in mice inoculated as newborns. One of these viruses is a recombinant mink cell focus-forming virus that induces T cell lymphomas, and the other is a replication-defective, fibroblast-transforming virus that induces early B lineage lymphomas in mice. Histologic and flow microfluorometric cell surface antigen analyses of primary and in vitro adapted tumors are presented in support of a modified scheme of hematopoietic cell development.     

The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice

Transgenic mice bearing a c-myc oncogene subjugated to the lymphoid-specific immunoglobulin heavy chain enhancer (E mu) develop clonal B lymphoid malignancies, but most young E mu-myc mice lack malignant clones. Their prelymphomatous state has allowed us to examine how constitutive c-myc expression influences B cell development. We find that early stages are overrepresented, even before birth. Pre-B cells of polyclonal origin increase greatly, while B cells develop in reduced number. Both the pre-B and the B cells appear to be in an active state, since they are larger than normal and a greater fraction are in the cell cycle. Enforced myc expression has thus favored proliferation over maturation. Hence, a normal function of c-myc may be to regulate differentiation as well as to promote cell cycling.