Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor.

The antigen receptors on B lymphocytes are cell-surface immunoglobulins. Antibodies against surface IgM (sIgM) coimmunoprecipitate several sIgM-associated proteins. Incubation of anti-IgM complexes with [gamma-32P]ATP leads to the phosphorylation on tyrosine of IgM-associated proteins including MB-1 and a protein of 72 kDa. Peptide mapping and reimmunoprecipitation experiments indicate that the 72-kDa phosphoprotein is PTK72, a protein-tyrosine kinase that is expressed at highest levels in B lymphocytes. MB-1 is also phosphorylated in immune complexes prepared with antibodies to PTK72, indicating that components of the IgM complex are associated with PTK72. In addition, PTK72 is associated with sIgD complexes isolated from spleen B lymphocytes. The cross-linking of sIgM antigen receptors on B lymphocytes leads to the rapid phosphorylation of PTK72 on tyrosine and to the activation of PTK72 as measured by autophosphorylation and by the phosphorylation of an exogenous substrate in anti-PTK72 immune complexes. These results suggest that the signaling cascade initiated by engagement of the B cell antigen receptor involves the increased enzymatic activity of PTK72, which is already present in a preformed antigen receptor complex.     

A second serogroup of Legionella erythra serologically indistinguishable from Legionella rubrilucens

N.A. SAUNDERS, N. DOSHI AND T.G. HARRISON. 1992. Twenty-two red-autofluorescent Legionella strains were identified serologically as either Legionella rubrilucens or L. erythra. A rRNA probe was used for restriction fragment length polymorphism (RFLP) analysis of the strains and the patterns generated were used as an additional method of identifying the strains to species level. In two instances strains which were identified as L. rubrilucens by serology appeared to belong to the species L. erythra by RFLP analysis. This apparent contradiction was resolved by measurements of DNA/DNA homology which confirmed the existence of a second serogroup of L. erythra serologically indistinguishable from L. rubrilucens.     

Systemic blood flow to the lung after bronchial artery occlusion in anesthetized sheep.

To compare the effectiveness of different embolizing agents in reducing or redistributing bronchial arterial blood flow, we measured systemic blood flow to the right lung and trachea in anesthetized sheep by use of the radioactive microsphere method before and 1 h after occlusion of the bronchoesophageal artery (BEA) as follows: injection of 4 ml ethanol (ETOH) into BEA (group 1, n = 5), injection of approximately 0.5 g polyvinyl alcohol particles (PVA) into BEA (group 2, n = 5), or ligation of BEA (group 3, n = 5). After occlusion, angiography showed complete obstruction of the bronchial vessels. There were no changes in tracheal blood flow in any of the groups. Injection of ETOH produced a 75 +/- 14% (SD) reduction in flow to the middle lobe (P less than 0.02) and a 75 +/- 13% reduction to the caudal lobe (P less than 0.01), whereas injection of PVA produced a smaller reduction in flow to these two lobes (41 +/- 66 and 51 +/- 54%, respectively). After BEA ligation there was a 52 +/- 29% reduction in flow to the middle lobe and a 53 +/- 38% reduction to the caudal lobe (P less than 0.05). This study has significant implications both clinically and experimentally; it illustrates the importance of airway collateral circulation, in that apparently complete radiological obstruction of the BEA does not necessarily mean complete obstruction of systemic blood flow. We also conclude that, in experimental studies in which the role of the bronchial circulation in airway pathophysiology is examined, ETOH is the agent of choice.     

Identification of tyrosine 67 in bovine brain myelin basic protein as a specific phosphorylation site for thymus p56lck.

The protein-tyrosine kinase p56lck exhibits a restricted substrate specificity in vitro but can efficiently phosphorylate bovine myelin basic protein (MBP). Results obtained from both peptide mapping and fast atom bombardment mass spectrometry indicate that tyrosine 67 in the sequence -Thr-Thr-His-Tyr67-Gly-Ser-Leu-Pro-Gln-Lys- in bovine MBP is the specific phosphorylation site. p56lck does not phosphorylate the acidic, cytoplasmic domain of erythrocyte band 3. In contrast, p40, another protein-tyrosine kinase purified from bovine thymus that readily phosphorylates band 3, does not phosphorylate MBP. Therefore, MBP and band 3 may prove to be useful substrates for distinguishing between various tyrosine kinases on the basis of substrate specificity. In addition, identification of the recognition sequence in MBP for p56lck may contribute to an understanding of the structural features of physiological substrates for this kinase.     

Osteogenin promotes reexpression of cartilage phenotype by dedifferentiated articular chondrocytes in serum-free medium

Chondrocytes lose their phenotypic traits, including type II collagen, after serial passage in monolayer cultures. Osteogenin, a bone morphogenetic protein, induces cartilage and bone in nonskeletal sites. This investigation examined the ability of osteogenin to promote the reexpression of cartilage phenotype by dedifferentiated chondrocytes obtained from rabbit articular cartilage. The results revealed that osteogenin, in synergism with selected growth factors, promoted the reexpression of type II collagen and proteoglycans by dedifferentiated chondrocytes in agarose. Insulin, a constituent of the basal medium, appeared to be essential for the colony-forming aspect of this phenomenon, since when insulin was replaced by insulin-like growth factor-1 colony formation did not occur. Epidermal growth factor, platelet-derived growth factor (PDGF), and basic fibroblast growth factor appeared to be an optimal combination for the action of osteogenin. Neutralizing antibodies to transforming growth factor-beta did not influence the response to osteogenin. It is noteworthy that, compared to freshly passaged cells, those stored in liquid nitrogen were not as responsive to osteogenin and growth factors. A higher concentration of fibroblast growth factor in conjunction with osteogenin and PDGF, increased the responsiveness of frozen cells only in part, as the Alcian blue-positive proteoglycan matrix was not restored completely.     

Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma

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Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

Climate‐driven diversity change in annual grasslands: Drought plus deluge does not equal normal

Climate forecasts agree that increased variability and extremes will tend to reduce the availability of water in many terrestrial ecosystems. Increasingly severe droughts may be exacerbated both by warmer temperatures and by the relative unavailability of water that arrives in more sporadic and intense rainfall events. Using long‐term data and an experimental water manipulation, we examined the resilience of a heterogeneous annual grassland community to a prolonged series of dry winters that led to a decline in plant species richness (2000–2014), followed by a near‐record wet winter (2016–2017), a climatic sequence that broadly resembles the predicted future in its high variability. In our 80, 5‐m² observational plots, species richness did not recover in response to the wet winter, and the positive relationship of richness to annual winter rainfall thus showed a significant weakening trend over the 18‐year time period. In experiments on 100, 1‐m² plots, wintertime water supplementation increased and drought shelters decreased the seedling survival and final individual biomass of native annual forbs, the main functional group contributing to the observed long‐term decline in richness. Water supplementation also increased the total cover of native annual forbs, but only increased richness within nested subplots to which seeds were also added. We conclude that prolonged dry winters, by increasing seedling mortality and reducing growth of native forbs, may have diminished the seedbank and thus the recovery potential of diversity in this community. However, the wet winter and the watering treatment did cause recovery of the community mean values of a key functional trait (specific leaf area, an indicator of drought intolerance), suggesting that some aggregate community properties may be stabilized by functional redundancy among species.     

Assessing uncertainties in crop and pasture ensemble model simulations of productivity and N2O emissions

Simulation models are extensively used to predict agricultural productivity and greenhouse gas emissions. However, the uncertainties of (reduced) model ensemble simulations have not been assessed systematically for variables affecting food security and climate change mitigation, within multi‐species agricultural contexts. We report an international model comparison and benchmarking exercise, showing the potential of multi‐model ensembles to predict productivity and nitrous oxide (N₂O) emissions for wheat, maize, rice and temperate grasslands. Using a multi‐stage modelling protocol, from blind simulations (stage 1) to partial (stages 2–4) and full calibration (stage 5), 24 process‐based biogeochemical models were assessed individually or as an ensemble against long‐term experimental data from four temperate grassland and five arable crop rotation sites spanning four continents. Comparisons were performed by reference to the experimental uncertainties of observed yields and N₂O emissions. Results showed that across sites and crop/grassland types, 23%–40% of the uncalibrated individual models were within two standard deviations (SD) of observed yields, while 42 (rice) to 96% (grasslands) of the models were within 1 SD of observed N₂O emissions. At stage 1, ensembles formed by the three lowest prediction model errors predicted both yields and N₂O emissions within experimental uncertainties for 44% and 33% of the crop and grassland growth cycles, respectively. Partial model calibration (stages 2–4) markedly reduced prediction errors of the full model ensemble E‐median for crop grain yields (from 36% at stage 1 down to 4% on average) and grassland productivity (from 44% to 27%) and to a lesser and more variable extent for N₂O emissions. Yield‐scaled N₂O emissions (N₂O emissions divided by crop yields) were ranked accurately by three‐model ensembles across crop species and field sites. The potential of using process‐based model ensembles to predict jointly productivity and N₂O emissions at field scale is discussed.     

Walking on ashes: insect trace fossils from Laetoli indicate poor grass cover associated with early hominin environments

More than 4000 insect trace fossils collected in recent years from Pliocene deposits at Laetoli in northern Tanzania provide new insights on early hominin palaeoenvironments. These trace fossils include: Fictovichnus gobiensis, Coprinisphaera murguiai, C. kheprii, Coprinisphaera ispp., Quirogaichnus isp., Teisseirei linguatus isp. nov., Celliforma ritchiei isp. nov., C. spirifer, C. germanica, C. cfr. curvata, Celliforma ispp., Rosellichnus isp., Vondrichnus planoglobus, Laetolichnus kwekai igen. et isp. nov. and Krausichnidae indet. They reveal that at least one species of moth, three dung beetles and five other coleopterans, nine taxa of solitary bees, and an indeterminate number of taxa of termites inhabited the Lower Laetolil environments. The Upper Laetolil environments, which have yielded a rich diversity of vertebrate fossils, including the early hominin Australopithecus afarensis and its putative footprints, supported several taxa of termites, one dung beetle, five other coleopterans, and eleven taxa of bees. The Upper Ndolanya environments, which have yielded the hominin Paranthropus aethiopicus, record four taxa of dung beetles, four other coleopterans, and two taxa of bees. The record of larval mortality and lack of intruder activity, revealed by the absence of emergence and intruder traces, may be associated with the anoxic/hypoxic conditions caused by the instantaneous burial of soils under thick volcanic ashes. The record of the Celliforma Ichnofacies in the Upper Laetolil environments indicates the dominance of shrubland to woodland with limited grass cover. This is supported also by the absence of Coprinisphaera, which suggests a scarcity of fresh grasses and a low abundance of large mammal grazers.