The Freter model: A simple model of biofilm formation

A simple, conceptual model of biofilm formation, due to R. Freter et al. (1983), is studied analytically and numerically in both CSTR and PFR. Two steady state regimes are identified, namely, the complete washout of the microbes from the reactor and the successful colonization of both the wall and bulk fluid. One of these is stable for any particular set of parameter values and sharp and explicit conditions are given for the stability of each. The effects of adding an anti-microbial agent to the CSTR are examined.Supported by NSF Grant DMS 0107439 and UTA Grant REP 14748717Supported by NSF Grant DMS 0107160     

Microampullary organs of a freshwater eel-tailed catfish,Plotosus (tandanus) tandanus

Whole body studies of Plotosus tandanus revealed that ampullary pores occur over the entire body of the fish, but are in higher concentrations in the head region. These pores give rise to a short canal (50-60 microm) produced by columnar epithelial cells bound together by tight junctions and desmosomes. At the junction of the canal and the ampulla, cuboidal epithelial cells make up the wall. The ampulla consists of layers of collagen fibers that surround flattened epithelial cells in the lateral regions and give rise to supportive cells that encase a small number of receptor cells (10-15). The ampullary wall comprises several types of cells that are adjoined via tight junctions and desmosomes between cell types. The ovoid receptor cells possess microvilli along the luminar apical area. Beneath this area, the cells are rich in mitochondria and rough endoplasmic reticulum. An unmyelinated neuron adjoins with each receptor cell opposite multiple presynaptic bodies. This form of microampulla has not been previously described within the Family Plotosidae.     

Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms

Altered mucosal integrity andincreased cytokine production, including tumor necrosis factor (TNF),are the hallmarks of inflammatory bowel disease (IBD). In this study,we addressed the role of TNF receptors (TNFR) on intestinal epithelialcell migration in an in vitro wound closure model. With mouse TNFR1 orTNFR2 knockout intestinal epithelial cells, gene transfection, andpharmacological inhibitors, we show a concentration-dependentreceptor-mediated regulation of intestinal cell migration by TNF. Aphysiological TNF level (1 ng/ml) enhances migration through TNFR2,whereas a pathological level (100 ng/ml) inhibits wound closure through TNFR1. Increased rate of wound closure by TNFR2 or inhibition by TNFR1cannot be explained by either increased proliferation orapoptosis, respectively. Furthermore, inhibiting Src tyrosine kinase decreases TNF-induced focal adhesion kinase (FAK) tyrosine phosphorylation and cellular migration. We therefore conclude thatTNFR2 activates a novel Src-regulated pathway involving FAK tyrosinephosphorylation that enhances migration of intestinal epithelial cells.

     

Vocal clans in sperm whales (Physeter macrocephalus)

Cultural transmission may be a significant source of variation in the behaviour of whales and dolphins, especially as regards their vocal signals. We studied variation in the vocal output of 'codas' by sperm whale social groups. Codas are patterns of clicks used by female sperm whales in social circumstances. The coda repertoires of all known social units (n = 18, each consisting of about 11 females and immatures with long-term relationships) and 61 out of 64 groups (about two social units moving together for periods of days) that were recorded in the South Pacific and Caribbean between 1985 and 2000 can be reliably allocated into six acoustic 'clans', five in the Pacific and one in the Caribbean. Clans have ranges that span thousands of kilometres, are sympatric, contain many thousands of whales and most probably result from cultural transmission of vocal patterns. Units seem to form groups preferentially with other units of their own clan. We suggest that this is a rare example of sympatric cultural variation on an oceanic scale. Culture may thus be a more important determinant of sperm whale population structure than genes or geography, a finding that has major implications for our understanding of the species' behavioural and population biology.     

Rho and p38 MAP kinase signaling pathways mediate LPA-stimulated hepatic myofibroblast migration

Although hepatic myofibroblast migration plays a key role in the liver's injury response, the signal transduction pathways mediating the migration of this cell type are uncertain. Recently, we reported that lysophosphatidic acid (LPA) stimulates the migration of hepatic myofibroblasts. The goal of this study was to test the hypothesis that rho and p38 MAP kinase signaling pathways mediate LPA-stimulated hepatic myofibroblast migration. We measured migration, myosin regulatory light chain and p38 MAP kinase phosphorylation, and contractile force generation by human hepatic myofibroblasts. LPA stimulated migration in a dose-dependent and saturable manner that was partially blocked by Y-27632, a rho-associated kinase inhibitor, as well as by SB-202190, a p38 MAP kinase inhibitor. LPA also induced myosin regulatory light chain phosphorylation and contractile force generation in a Y-27632 dependent, and SB-202190 independent fashion. Moreover, LPA stimulated a dose-dependent and saturable phosphorylation of p38 MAP kinase, which was not altered by Y-27632 or C3 transferase, a rho inactivator. These novel results suggest that LPA stimulates hepatic myofibroblast migration via distinct pathways that signal through rho and p38 MAP kinase.     

Transgenic expression of stromal cell-derived factor-1/CXC chemokine ligand 12 enhances myeloid progenitor cell survival/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo

Hemopoiesis is regulated in part by survival/apoptosis of hemopoietic stem/progenitor cells. Exogenously added stromal cell-derived factor-1 ((SDF-1)/CXC chemokine ligand (CXCL)12) enhances survival/antiapoptosis of myeloid progenitor cells in vitro. To further evaluate SDF-1/CXCL12 effects on progenitor cell survival, transgenic mice endogenously expressing SDF-1/CXCL12 under a Rous sarcoma virus promoter were produced. Myeloid progenitors (CFU-granulocyte-macrophage, burst-forming unit-erythroid, CFU-granulocyte-erythrocyte-megakaryocyte-monocyte) from transgenic mice were studied for in vitro survival in the context of delayed addition of growth factors. SDF-1-expressing transgenic myeloid progenitors were enhanced in survival and antiapoptosis compared with their wild-type littermate counterparts. Survival-enhancing effects were due to release of low levels of SDF-1/CXCL12 and mediated through CXCR4 and G(alpha)i proteins as determined by ELISA, an antagonist to CXCR4, Abs to CXCR4 and SDF-1, and pertussis toxin. Transgenic effects of low SDF-1/CXCR4 may be due to synergy of SDF-1/CXCL12 with other cytokines; low SDF-1/CXCL12 synergizes with low concentrations of other cytokines to enhance survival of normal mouse myeloid progenitors. Consistent with in vitro results, progenitors from SDF-1/CXCL12 transgenic mice displayed enhanced marrow and splenic myelopoiesis: greatly increased progenitor cell cycling and significant increases in progenitor cell numbers. These results substantiate survival effects of SDF-1/CXCL12, now extended to progenitors engineered to endogenously produce low levels of this cytokine, and demonstrate activity in vivo for SDF-1/CXCL12 in addition to cell trafficking.     

A live,attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3' untranslated region is highly attenuated and immunogenic in monkeys

The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes.     

Interaction between human respiratory syncytial virus (RSV) M2-1 and P proteins is required for reconstitution of M2-1-dependent RSV minigenome activity

We have investigated protein-protein interactions among the respiratory syncytial virus (RSV) RNA polymerase subunits using affinity chromatography. Here we demonstrate a novel interaction of P and M2-1 proteins. Phosphorylation of either M2-1 or P appears to be dispensable for this interaction. Internal deletions within P mapped the M2-1-binding domain to a region between residues 100 and 120. Alanine-scanning mutagenesis within this region of P revealed that substitution of any one of the three residues, L101, Y102, and F109, prevented both M2-1 and P binding and expression of an M2-1-dependent luciferase reporter gene. However, these same mutations did not prevent the activity of an M2-1-independent chloramphenicol acetyltransferase minigenome, suggesting that these residues of P specifically affect M2-1-P interaction. On the basis of these observations, it is possible that the interaction between RSV M2-1 and P proteins is important for viral replication.     

Periodic coexistence of four species competing for three essential resources

We show the existence of a periodic solution in which four species coexist in competition for three essential resources in the standard model of resource competition. By assuming that species i is limited by resource i for each i near the positive equilibrium, and that the matrix of contents of resources in species is a combination of cyclic matrix and a symmetric matrix, we obtain an asymptotically stable periodic solution of three species on three resources via Hopf bifurcation. A simple bifurcation argument is then employed which allows us to add a fourth species. In principle, the argument can be continued to obtain a periodic solution adding one new species at a time so long as asymptotic stability can be assured at each step. Numerical simulations are provided to illustrate our analytical results. The results of this paper suggest that competition can generate coexistence of species in the form of periodic cycles, and that the number of coexisting species can exceed the number of resources in a constant and homogeneous environment.