Comitogenic effect of solid-phase immobilized anti-1F7 on human CD4 T cell activation via CD3 and CD2 pathways

We have recently developed a mAb, anti-1F7, which defines a family of structures found to include the molecule recognized by anti-Ta1 (CD26). In this paper, we demonstrated that binding of 1F7 by solid-phase immobilized anti-1F7 mAb but not anti-Ta1 mAb has a comitogenic effect by inducing proliferation of human CD4+ T lymphocytes in conjunction with submitogenic doses of anti-CD3 or anti-CD2. The proliferative response induced via the CD3-1F7 or CD2-1F7 pathways is associated with the IL-2 autocrine pathway, including IL-2 production. IL-2R expression and anti-IL-2R (Tac) inhibition. Furthermore, solid-phase immobilization of anti-1F7 but not anti-Ta1 acts in conjunction with submitogenic doses of PMA to mediate a comitogenic effect in the absence of anti-CD3 or anti-CD2, leading to CD4+ T cell proliferation. PMA treatment, in the meantime, leads to enhanced expression of 1F7 on the T cell surface. Despite its functional association with both pathways of activation, however, the 1F7 structure is not comodulated with the CD3/TCR complex nor the CD2 molecule. These findings thus suggest that the CD26 Ag is involved in CD3 and CD2-induced human CD4+ T cell activation.     

VH sequence of a human anti-Sm autoantibody. Evidence that autoantibodies can be unmutated copies of germline genes

The utilization of germline genes for the synthesis of autoantibodies has been suspected for many years based on the presence of cross-reactive idiotypes among patients as well as in some healthy first-degree relatives of patients with several autoimmune diseases including SLE. One such system of idiotypes involves anti-Sm antibodies, which are highly specific for SLE. To definitively establish the utilization of germline genes in the Sm system, we produced human-human B cell hybridomas from a patient with SLE who had circulating anti-Sm antibodies. One stable hybridoma designated 4B4 secretes an IgM-kappa mAb that binds Sm and shares idiotypic determinants with other anti-Sm antibodies. A second anti-Sm antibody (3C3), isolated from the same patient was also studied. Oligo(dT) priming was used to produce cDNA corresponding to full length IgM. Sequence analysis revealed that the VH gene segment (1-96) of 4B4 is identical to a VH sequence previously detected in a fetal liver cDNA library by Schroeder and his co-workers as well as a germline VH recently described by Berman and his associates. The identity of a lupus mAb and sequences derived from unrelated individuals provides strong evidence that this autoantibody is a direct copy of a germline gene.     

Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicity.

The recent discovery that point mutations in the beta/A4 amyloid precursor protein may be the cause of certain forms of familial Alzheimer's disease provides strong support for the view that a thorough understanding of the metabolism of this protein may elucidate the pathogenesis of most forms of the disease and thus serve as a basis for rational prevention and therapy. Here we show that overexpression of a portion of the amyloid precursor protein molecule produces at least four distinct fragments of the COOH-terminus of amyloid precursor protein, suggesting altered proteolysis of amyloid precursor protein, and that such overexpression is associated with cytotoxicity. The degree of toxicity in the P19 cell culture model (differentiating mouse embryonal carcinoma cells) is shown to be related to the two larger novel COOH-terminal protein fragments (16 and 14 kilodalton), as well as to levels of expression of these two fragments. The toxicity is manifested in several differentiated cell lineages, including neuronal cells.     

Inheritance of cellulose- and lignin-degrading ability as well as endoglucanase isozyme pattern in Dichomitus squalens

Summary The progeny of Dichomitus squalens CBS-432-34 is heterogeneous with respect to specific growth rate on glucose, cellulolytic ([U¹⁴C]cellulose ¹⁴CO₂) and ligninolytic ([¹⁴C]synthetic lignin ¹⁴CO₂) activities with little correlation between these metric characters. Variations do not show clear-cut phenotypes but rather a continuous range between extreme values pointing to multigenic control of these characters. Most homocaryons showed decreased cellulolytic or ligninolytic activity compared to the parent dicaryon. However a few homocaryons were comparable or even superior to the parent dicaryon for ligninolytic or cellulolytic activity with no correlation between each factor. Strains with reduced cellulolytic activity and altered isozyme patterns of endoglucanases were isolated in the progeny of D. squalens CBS-432-34. While the parent strain produced three main endoglucanase multiple enzymes designated EnI, EnII and EnIII, several strains in the progeny produced a different multiple enzyme pattern. In contrast to the quantitative ability to degrade cellulose, multiple enzyme pattern variation in the progeny did not show continuous variations. characterization of heterocaryon phenotypes derived from Ien⁺ and Ien 1 homocaryons and first filial generation (f1) analysis showed that genetic control of the multiple enzyme pattern (Ien 1 phenotype) in D. squalens is complex. Offprint requests to: E. Odier     

Overexpressions of cDNAs for β-Amyloid Precursor Proteins 695, 751, and 770 Enhance the Secretion of β-Amyloid Precursor Protein Derivatives and the Survival of P19-Derived Neurons

Abstract: P19 is a C3H mouse-derived line of multipotent embryonic carcinoma cells that differentiate into neural cells. P19 cell clones overexpressing the three major forms of β-amyloid precursor protein from their cDNA constructs were established. Unlike a previous study in which P19-derived neurons had a limited α-secretase activity, all of these clones produced significant amounts of secreted β-amyloid precursor protein. When treated with retinoic acid, these transformed lines differentiated into neurons and survived better than did nontransformed parental P19 cells. Furthermore, P19-derived neurons survived better in medium conditioned by the transformed P19 line, and survival was reduced by immunoabsorption with an antibody to β-amyloid precursor protein. These results suggest neurotrophic effects of secreted β-amyloid precursor protein and contrast with a previous report in which overexpression of a full-length cDNA for β-amyloid precursor protein led to degeneration of P19-derived neurons. Western blot analysis suggested that this difference might result from different levels of expression of putative neurotoxic C-terminal fragments of β-amyloid precursor protein; moreover, P19-derived neurons differ from P19 stem cells in the processing of these C-terminal fragments.     

Metabolite effectors for short-term nitrogen-dependent enhancement of phosphoenolpyruvate carboxylase activity and decrease of net sucrose synthesis in wheat leaves

It has been demonstrated previously that field pea (Pisum sativum L. cv. Express) grown in hydroponic culture on a complete nutrient solution with low NH₄⁺ concentrations (<0.5 mM) will produce a larger than normal proliferation of nodules. Peas grown in the absence of mineral N in hydroponic culture have been shown to rapidly autoregulate nodulation, forming a static nodule number by 14 to 21 days after planting. The present study further characterizes the effect of NH₄⁺ concentration in hydroponic culture on nodulation and nodule growth. Peas were grown continually for 4 weeks at NH₄⁺ concentrations that were autoregulatory (0.0 mM), stimulatory (0.2 mM) or inhibitory (1.0 mM), or peas were transferred between autoregulatory or NH₄⁺ inhibited and stimulatory solutions after 2 weeks. The peas nodulated as expected when grown under constant autoregulatory, stimulatory or inhibitory concentrations of NH₄⁺. When peas were transferred from the inhibitory (1.0 mM) to the stimulatory solution (0.2 mM) a massive proliferation of nodule primordia over the entire root system was observed within 3 days of the transfer. When they were transferred from the autoregulatory (0.0 mM) to the stimulatory (0.2 mM) solution a 10-day delay occurred before a proliferation in nodule primordia occurred at distal regions of the root system. These findings support our hypothesis that low concentrations (<1.0 mM) of NH₄⁺ in hydroponic culture cause a suppression of autoregulation in pea. In addition, the temporal and spatial differences in nodule proliferation between transfer treatments demonstrate at a whole plant level that autoregulation and NH₄⁺ inhibition suppress early nodule development via different mechanisms.     

Global mangrove root production,its controls and roles in the blue carbon budget of mangroves

Mangroves are among the most carbon-dense ecosystems worldwide. Most of the carbon in mangroves is found belowground, and root production might be an important control of carbon accumulation, but has been rarely quantified and understood at the global scale. Here, we determined the global mangrove root production rate and its controls using a systematic review and a recently formalised, spatially explicit mangrove typology framework based on geomorphological settings. We found that global mangrove root production averaged ~770 ± 202 g of dry biomass m⁻² year⁻¹ globally, which is much higher than previously reported and close to the root production of the most productive tropical forests. Geomorphological settings exerted marked control over root production together with air temperature and precipitation (r² ≈ 30%, p < .001). Our review shows that individual global changes (e.g. warming, eutrophication, drought) have antagonist effects on root production, but they have rarely been studied in combination. Based on this newly established root production rate, root-derived carbon might account for most of the total carbon buried in mangroves, and 19 Tg C lost in mangroves each year (e.g. as CO₂). Inclusion of root production measurements in understudied geomorphological settings (i.e. deltas), regions (Indonesia, South America and Africa) and soil depth (>40 cm), as well as the creation of a mangrove root trait database will push forward our understanding of the global mangrove carbon cycle for now and the future. Overall, this review presents a comprehensive analysis of root production in mangroves, and highlights the central role of root production in the global mangrove carbon budget.     

Asymmetric effects of daytime and nighttime warming on alpine treeline recruitment

Trees at their upper range limits are highly sensitive to climate change, and thus alpine treelines worldwide have changed their recruitment patterns in response to climate warming. However, previous studies focused only on daily mean temperature, neglecting the asymmetric influences of daytime and nighttime warming on recruitments in alpine treelines. Here, based on the compiled dataset of tree recruitment series from 172 alpine treelines across the Northern Hemisphere, we quantified and compared the different effects of daytime and nighttime warming on treeline recruitment using four indices of temperature sensitivity, and assessed the responses of treeline recruitment to warming-induced drought stress. Our analyses demonstrated that even in different environmental regions, both daytime and nighttime warming could significantly promote treeline recruitment, and however, treeline recruitment was much more sensitive to nighttime warming than to daytime warming, which could be attributable to the presence of drought stress. The increasing drought stress primarily driven by daytime warming rather than by nighttime warming would likely constrain the responses of treeline recruitment to daytime warming. Our findings provided compelling evidence that nighttime warming rather than daytime warming could play a primary role in promoting the recruitment in alpine treelines, which was related to the daytime warming-induced drought stress. Thus, daytime and nighttime warming should be considered separately to improve future projections of global change impacts across alpine ecosystems.