Synthesis and biological properties of Pachastrissamine (jaspine B) and diastereoisomeric jaspines

The synthesis of isomeric jaspines (anhydro phytosphingosines), arising from intramolecular cyclization of the corresponding phytosphingosines with different configurations at C3 and C4 positions of the sphingoid backbone, is reported. Natural jaspine B is the most cytotoxic isomer on A549 cells and it induces cell death in a dose-dependent manner. The cytotoxicity of jaspine B has been correlated with a significant increase of intracellular dihydroceramides, which seem to play an active role in autophagy.     

A Novel Jaspine BCeramide Hybrid Modulates Sphingolipid Metabolism

A new sphingolipid hybrid molecule was designed to assemble, within a tail‐to‐tail double‐chain structure, the ceramide hydrophilic moiety and the tetrahydrofuran pharmacophore of jaspine B, a natural product known to interfere with sphingolipid metabolism. This compound was prepared through acylation of sphingosine with a jaspine B derivative bearing a COOH group in the terminal position of the aliphatic backbone. This new hybrid molecule was evaluated for its capacities to affect melanoma cell viability and sphingolipid metabolism. While retaining the cytotoxicity of ceramide itself, this compound was shown to lower the sphingomyelin cellular levels and significantly enhance the production of sphingosine‐1‐phosphate, thus representing a novel sphingolipid metabolism modulator.     

Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C

Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their inhibitory effects against SphKs. All eight stereoisomers exhibited moderate to potent inhibitory activity against SphK1 and SphK2. Inhibitory effects were profiled against protein kinase C (PKC) isoforms by in vitro experiments. Atypical PKCs (PKCζ and PKCι) were inhibited by several pachastrissamine stereoisomers. The improved activity over N,N-dimethylsphingosine suggests that the cyclic scaffold in pachastrissamines facilitates potential favorable interactions with SphKs and PKCs.     

Discovery of novel jaspine B analogues as autophagy inducer

A series of 2-alkylaminomethyl jaspine B analogues were synthesized and evaluated for their cytotoxic effects on human lung adenocarcinoma, breast cancer, and prostate cancer cell lines and a mouse melanoma cell line. Most of the compounds exhibited moderate to good activity against the cancer cell lines. Compound 7f showed the best overall cytotoxicity on PC-3 cells (IC₅₀?=?0.85?μM). Further mechanistic studies revealed that compound 7f induced marked changes in PC-3 cell morphology, disrupted the mitochondrial membrane potential, and increased expression of the autophagy proteins beclin-1, LC3, and P62.     

B7, a B-cell-restricted antigen that identifies preactivated B cells

After activation with antigen or mitogen, a number of cell surface proteins appear that are not expressed on resting B cells. To date, a number of B lineage restricted and associated activation antigens have been reported that appear at distinct intervals after in vitro activation. In this report, we describe a new B lineage restricted activation antigen (B7) that appears within 24 hr of in vitro stimulation. The expression of B7 antigen, which is detected on a minor subpopulation of B cells isolated from peripheral blood and lymphoid tissues, is strongly induced following stimulation with either anti-immunoglobulin or Epstein-Barr virus. In contrast, B7 was not detected on resting or activated T cells or monocytes. The B7 antigen was expressed on a subset of B cell lines and B cell neoplasms, but was not detected on leukemias and lymphomas of T cell or myeloid origin. B7 was distinguished from other B cell restricted and associated activation antigens by its unique pattern of expression on a variety of hemopoietic cell lines. The biochemical characterization of B7, that it is a single chain protein of 60 kDa, further distinguishes it from other B cell activation antigens. The functional importance of the B7 antigen was demonstrated when splenic B cells were fractionated into the B7+ and B7- populations. The peak of proliferation in response to anti-Ig, appeared earlier within the B7+ population. These studies suggest that B7 antigen identifies a subpopulation of B cells that are preactivated or primed in vivo, and have an accelerated response to subsequent activation via cross-linking of surface Ig.     

B cell surface glycoprotein induced during growth response: molecular structure and expression pattern

We present the molecular characterization of a cell surface antigen, B 7.2, that is expressed on activated B lymphocytes. The BCL1 and CH12 B lymphoma cells express the B 7.2 antigen constitutively. In small resting B cells from spleen, the B 7.2 expression is induced during polyclonal growth in response to mitogenic stimulation. B 7.2 expression also occurs with a significant frequency in cells from fresh lymphoid tissues. The endogenous expression of the B 7.2 antigen is high in spleen and lymph nodes, and is undetectable in the thymus. The B 7.2 antigen is a microheterogeneous 45,000 to 50,000 dalton glycoprotein with a single polypeptide chain, intramolecular S--S bonds, and N-linked glycan moieties. The folded structure of the B 7.2 antigen appears to contain a domain with hydrophilic properties exposed on the cell surface and a hydrophobic segment that may comprise a transmembrane portion. Considering the observed expression pattern and the molecular structure, we speculate that the B 7.2 antigen has a specific function in regulation of B cell activation, perhaps as a receptor for a regulatory ligand or as a ligand recognized by other B or T cells.     

Comparison of boron uptake and translocation in two vetiver genotypes and evaluation of boron removal efficiency of vetiver floating islands

The objectives of this study were to identify genotypic differences in the uptake and translocation of boron (B) in vetiver (Chrysopogon zizanioides L.), a promising species in B phytoremediation, and to determine the efficiency of vetiver floating island system in B phytoremediation. Changes in plant biomass and B uptake and translocation were determined in two vetiver genotypes, Sierra and Sunshine, cultured hydroponically in a nutrient solution and exposed to six different B concentrations for 7 d and 14 d. The efficiency of B removal by Sierra (a high B accumulative genotype) grown in floating islands was also determined. Shoot B concentration differed significantly between the two genotypes but differences in root concentration were not significant. Root to shoot B transfer and B uptake ability were higher in Sierra than in Sunshine. The uptake and translocation of B was affected by B concentration and time of exposure. Sierra plants grown in floating islands were more efficient in B removal at lower B concentrations. Most of the B removed accumulated in the middle-upper sections of old leaves. Sierra is more suitable for the removal of B from wastewaters than Sunshine, especially in vetiver floating island system.     

Genetic systems of red cell blood groups in goats.

Evidence is presented for six genetic systems of goat red cell blood groups. The A system presently consists of one specificity, two alleles, two phenotypes (A1 and no-A1) and appears to be homologous to the A system of sheep. The B system, like its homologue in sheep, is very complex. Fourteen of 21 specificities detected in the present study, i.e. B2, B3, B4, B5, B7, B8, B9, B10, B11, B14, B15, B16, B17 and B20, belong to the B system which involves a large number of phenogroups (31 different B phenogroups identified in 26 sires). Because of their homology with sheep C and R systems, two other genetic systems of goat blood groups are named C and R respectively. Each of the two goat systems is presently a one blood group specificity, two phenotype (C12 and no-C12; R and no-R detectable on the red cells) two allele system. Two specificities, namely E6 and E18, belong to a genetic system called E in which four phenotypes are under the control of two alleles codominant and one recessive at a single locus. The F system involves but a single pair of alleles and two phenotypes (F19 and no-F19). Because of its low frequency in the goats tested, the X13 specificity remains unassigned.     

Update on Boron in Higher Plants - Uptake, Primary Translocation and Compartmentation

Abstract: This review focuses on the uptake and primary translocation of boron (B), as well as on the subcellular compartmentation of B and its role in cell walls of higher plants. B uptake occurs via passive diffusion across the lipid bilayer, facilitated transport through major intrinsic proteins (MIPs), and energy-dependent transport through a high affinity uptake system. Whereas the first two represent passive uptake systems, which are constitutively present, the latter is induced by low B supply and is able to establish a concentration gradient for B between the root symplasm and the external medium. At high B supply, a substantial retention of B can be observed at xylem loading, and passive processes are most likely responsible for that. At low B supply, another energy-dependent high affinity transport system for B seems to be induced which establishes an additional concentration gradient between root symplasm and the xylem. The possible significance of all these processes at various B supplies is discussed. The role of soluble B complexes in uptake and primary translocation of B has been evaluated, but the few data available do not allow comprehensive conclusions to be drawn. In any case, there are no indications that soluble B complexes play a major role in either uptake or primary translocation of B. The subcellular compartmentation of B still remains a matter of controversy, but it is unequivocally clear that B is present in all subcellular compartments (apoplasm, cell wall, cytosol and vacuole). The relative distribution of B between these is dependent on plant species and experimental conditions and may vary greatly. Recent results on the well-established role of B in cell walls are summarized and their physiological significance discussed.     

Histamine-sensitizing Factor, Mouse-protective Antigens, and Other Antigens of Some Members of the Genus Bordetella

The three species of the genus Bordetella-B. pertussis, B. parapertussis, and B. bronchiseptica-have many antigens in common. Studies on representative strains of these species have shown that there are only a few specific antigens in each species. Whole-cell vaccines and extracts from B. pertussis contained specific mouse-protective antigen and a histamine-sensitizing factor. In addition, whole-cell vaccines and some saline extracts protected mice against intracranial challenge with B. bronchiseptica. Cells and a saline extract of B. parapertussis also protected against B. bronchiseptica but not against B. pertussis. Whole cells of B. bronchiseptica protected against B. bronchiseptica, but only one of three saline extracts protected against this challenge. Neither whole cells nor saline extracts from B. bronchiseptica protected against B. pertussis. The antigen in B. pertussis responsible for cross-protection against B. bronchiseptica was less resistant to heat than the protective antigen in B. bronchiseptica. Since histamine-sensitizing factor was not detected in B. bronchiseptica or B. parapertussis cells or extracts, this factor is not required to protect mice against B. bronchiseptica challenge. Whether B. pertussis vaccines protected against B. bronchiseptica by a nonspecific mechanism was not established, but it is clear that the specific antigen responsible for protection against B. pertussis was found only in B. pertussis and not in B. bronchiseptica or B. parapertussis.     

A revision of Sabella, Bispira and Stylomma (Polychaeta: Sabellidae)

Sabella is rediagnosed to include only species that have spiralled fascicles of abdominal chaetae, first thoracic shield with straight anterior border and radioles that lack composite eyes and flanges. Spirographis spallanzanii is synonymous with Sabella penicillus . The type of the genus is discussed and a neotype designated. The only other species retained in Sabella are S. pavonina and S. discifera ( = Branchiomma linaresi , once misplaced in Megalomma , but abdominal fascicles of Megalomma form transverse rows). Most species formerly placed in Sabella are transferred to Bispira , having C-shaped fascicles of abdominal chaetae, first thoracic shield with a 'W-shaped anterior border and, in most species, radioles with paired composite eyes and flanges. Bispira , with B. volutacornis as the type species, is rediagnosed to include B. crassicomis, B. fabricii, B. melanostigma, B. tricyclia, B. viola, B. manicata, B. poricfera, B, mariae, B. elegans, B. brunnea, B. guinensis, B. secusolutus, B. wireni, B. oatesiana, B. spirobranchia, B. pacifica, B. monroi , and B. turneri , many of which are described fully for the first time. Only five of these form bispiral crowns (bispirality is useful only specifically and occurs in other genera) and one, B. tricyclia , has a unispiral crown. Sabella palmata Quatrefages, the type of Stylomma is redescribed and its synonyms discussed. This genus has abdominal fascicles like those of Bispira , but radiolar eyes like those of Megalomma . The relative advantages of chaetal arrangement and eye position are discussed.     

Anti-Rous sarcoma response of major histocompatibility (B) complex haplotypes B23, B24 and B30

Responses to Rous sarcoma virus (RSV) induced tumours were studied in UNH 105, a non-inbred line of New Hampshire chickens. Six single male matings encompassing a total of 50 dams produced 345 progeny which segregated for B complex genotypes B23/B23, B23/B24, B23/B30, B24/B24, B24/B30 and B30/B30. Six-week-old chicks were wingweb inoculated with a pseudotype of Bryan high titre Rous sarcoma virus, BH RSV (RAV-1). Tumours were scored for size six times over a 10-week period post-inoculation. Each chick was assigned a tumour profile index (TPI) as an indicator of immunological response. The number of days to death (DTD) was recorded for 148 chicks with terminal tumours. Genotypes B23/B23, B23/B24 and B23/B30, with TPIs of 1.8, 1.7 and 2.0 respectively, did not differ significantly from each other, suggesting dominance of response of B23 over B24 and B30 haplotypes. B24/B30 chicks with the highest TPI (3.4) and shortest DTD (34.6) were significantly different from B30/B30 (2.8; 41.6) but not from B24/B24 (3.1; 34.9) suggesting dominance of response of the B24 haplotype over B30 in the absence of B23.     

Major histocompatibility (B) complex and sex effects on the phytohaemagglutinin wattle response

The influence of the major histocompatibility (B) complex and sex on the phytohaemagglutinin (PHA) wattle response was studied in 136 segregants (B2/B2, B2/B5 and B5/B5) of a fourth generation cross between inbred lines 6(1) and 15(1). At 6 weeks of age, chickens were injected with 100 micrograms purified PHA-P. Wattle thickness measurements were taken 4, 24, 48, 72 and 96 h after injection. Analysis of variance showed that 4 h after injection, males had a significantly higher response than females but the sex-genotype interaction was also significant. Females had higher responses than males 24 and 48 h after injection as a consequence of more rapid development and earlier resolution of the reaction in males. B2/B2 chickens had significantly lower responses than B5/B5 chickens 72 and 96 h after injection, signifying a faster late resolution phase in the B2/B2 genotype. The developmental and early resolution phases of the PHA wattle response were influenced by sex while the late resolution phase was influenced by B genotype.     

Retranslocation of boron in broccoli and lupin during early reproductive growth

The objective of the present study was to determine if boron (B) retranslocation depends on plant-B status and external-B supply. The stable ¹⁰B isotope was supplied to the root system of broccoli ( Brassica oleracea var. italica Plenck cv. Commander) and lupin ( Lupinus albus L. cv. Ultra) plants to provide a quantitative picture of B distribution during early reproductive development. Regardless of the B regime (i.e. continuous supply with luxury, sufficient or deficient B; transfer at inflorescence emergence from either a luxury- or sufficient-B supply to a deficient one) and whether ¹⁰B was acquired before or during inflorescence development, a significant proportion of the B recovered in broccoli florets and lupin fruit was ¹⁰B enriched. B acquired during inflorescence development was an important source of B for reproductive structures, but the relative importance of B acquired before and after inflorescence emergence appeared to be species dependent. The occurrence of B retranslocation was not dependent upon the induction of B deficiency. The concentrations of B in phloem exudates (0.38 to 0.03 mM) were 4- to 23-fold those in xylem sap, and more similar to the concentrations in the reproductive structures (0.86 to 0.07 mM) than those in source leaves (2.4 to 0.19 mM). The decreasing acropetal gradient of tissue-B concentrations with luxury-B supply declined dramatically or was reversed in plants grown with sufficient or deficient B. The data are consistent with B being a phloem-mobile element, and suggest that newly acquired B is particularly important during the early reproductive growth of plants.     

B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes

The characterization of a new B cell-specific antigen (B4) is described in this report. With the use of a monoclonal antibody to B4, it was shown that B4 is present on B cells isolated from peripheral blood and lymphoid organs, on cell lines derived from normal and malignant B cells, and on tumor cells isolated from patients with B cell-derived neoplasms. B4, in contrast, was not detected on normal, activated, or malignant cells of T or myeloid origin. The B4 antigen is distinct from known B cell antigens, including sIg, Ia, B1, B2, Fc, and C3. Examination of mitogen-stimulated B lymphocytes suggests that the B4 antigen initially increases with B cell activation and then is lost at the terminal stage of B cell differentiation. Moreover, the observation that B4 is expressed on almost all early B cell tumors suggests that it may precede B1, CALLA, cytoplasmic mu, and B2 in early B cell ontogeny.     

The binding of monoclonal antibodies to cell surface molecules. Quantitative analysis of the reactions and cross-reactions of an antibody (MB40.3) with four HLA-B molecules

The MB40.3 monoclonal antibody binds to four distinct HLA-B molecules; B7, B40, B40*, and B27. With Fab' fragments only the interaction with B7 and B40 was detected and the affinity for both was the same (1-2 X 10(8) M-1) suggesting the epitope is shared by the two molecules. Unlike many antibodies for which low affinity is due to a high-dissociation constant, that of MB40.3 results from a very low-association rate constant, coupled with a low-dissociation constant. In consequence, the affinity and avidity of Fab', F(ab')2, and IgG for B7 and B40 were found to be of a similar magnitude, soluble B7 was a more efficient competitor for antibody than cell surface B7 and in practice antibody bivalency was of little importance. The forward rate constant could be increased by removing Fc from the antibody or by removing sialic acid from the cells by treatment with neuraminidase. The neuraminidase treatment also produced an increase in the number of detectable cell surface HLA-A,B molecules. The affinity of MB40.3 for B40* and B27 was estimated to be less than 4 X 10(6) as no binding with Fab' was detected due to a high-dissociation rate. For these two HLA-B molecules bivalent attachment was critical, and it increased the strength of interaction with cell surface B40* and B27 to a point where the avidities were comparable to those obtained with B7 and B40, with B40* interacting more strongly than B27. The epitopes recognized by MB40.3 on B40* and B27 were thus shown to be structurally different from each other and from those on B7 and B40. The properties of this antibody contrast with those of other anti-HLA-A,B we have studied (Ways, J.P., and Parham, P. (1983) Biochem. J. 216, 423-432).