Embedded Complexity of Evolutionary Sequences.

Multiple pathways and outcomes are common in evolutionary sequences for biological and other environmental systems due to nonlinear complexity, historical contingency, and disturbances. From any starting point, multiple evolutionary pathways are possible. From an endpoint or observed state, multiple possibilities exist for the sequence of events that created it. However, for any observed historical sequence-e.g., ecological or soil chronosequences, stratigraphic records, or lineages-only one historical sequence actually occurred. Here, a measure of the embedded complexity of historical sequences based on algebraic graph theory is introduced. Sequences are represented as system states S(t), such that S(t - 1) ≠ S(t) ≠ S(t + 1). Each sequence of N states contains nested subgraph sequences of length 2, 3, …, N - 1. The embedded complexity index (which can also be interpreted in terms of embedded information) compares the complexity (based on the spectral radius λ1) of the entire sequence to the cumulative complexity of the constituent subsequences. The spectral radius is closely linked to graph entropy, so the index also reflects information in the sequence. The analysis is also applied to ecological state-and-transition models (STM), which represent observed transitions, along with information on their causes or triggers. As historical sequences are lengthened (by the passage of time and additional transitions or by improved resolutions or new observations of historical changes), the overall complexity asymptotically approaches λ1 = 2, while the embedded complexity increases as N2.6. Four case studies are presented, representing coastal benthic community shifts determined from biostratigraphy, ecological succession on glacial forelands, vegetation community changes in longleaf pine woodlands, and habitat changes in a delta.

Controls on sediment delivery in coastal plain rivers.

Rivers crossing coastal plains are often inefficient conveyors of sediment, so that changes in upstream sediment dynamics are not evident at the river mouth. Extensive accommodation space and low stream power often result in extensive alluvial storage upstream of estuaries and correspondingly low sediment loads at the river mouth. However, gaging stations with sediment records are typically well upstream of the coast, and thus tend to overestimate sediment yields by under-representing the lower coastal plain and because there is often a net loss of sediment in lower coastal plain reaches. Studies of alluvial sediment storage have generally focused on accommodation space, but, using examples from Texas, we show that low transport capacity controlled largely by slope is a crucial factor.

Combination of inhibitors of lymphocyte activation (hydroxyurea, trimidox, and didox) and reverse transcriptase (didanosine) suppresses development of murine retrovirus-induced lymphoproliferative disease.

The ribonucleotide reductase inhibitor hydroxyurea (HU) has demonstrated some benefit as a component of drug cocktails for the treatment of HIV-1 infection. However, HU is notoriously myelosuppressive and often administered only as salvage therapy to patients with late-stage disease, potentially exacerbating the bone marrow toxicity of HU. In this report we have compared the antiviral effects of HU and two novel RR inhibitors trimidox (3,4,5-trihydroxybenzamidoxime) and didox (3,4-dihydroxybenzohydroxamic acid) in combination with didanosine (2,3-didoxyinosine; ddI) in the LPBM5 MuLV retrovirus model (murine AIDS). We also evaluated the effects of these drug combinations on the hematopoietic tissues of LPBM5 MuLV-infected animals. The combination of RR inhibitors and ddI was extremely effective (DX>TX>HU) in inhibiting development of retrovirus-induced disease (splenomegaly, hypergammaglobulinemia, activated B-splenocytes and loss of splenic architecture). In addition, relative levels of proviral DNA were significantly lower in combination drug-treated animals compared to infected controls. Evaluation of femur cellularity, numbers of marrow-derived myeloid progenitor cells (CFU-GM and BFU-E) and peripheral blood indices revealed that TX and DX in combination with ddI were well-tolerated. However, treatment with HU and ddI induced moderate myelosuppression. These data demonstrate that RR inhibitors in combination with ddI provide significant protection against retroviral disease in murine AIDS. Moreover, the novel RR inhibitors TX and DX appear to be more effective and less myelosuppressive than HU when administered with ddI in this model.

Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox: novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea.

Recently, the use of the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) in combination with nucleoside analogs has gained attention as a potential strategy for anti-HIV-1 therapy. However, appeal for the long-term use of HU in HIV-1 infection may be limited by its propensity to induce hematopoietic toxicity. We report a comparison of the efficacy and bone marrow toxicity of HU (400 and 200 mg/kg/day) with the novel RR inhibitors and free radical-scavenging compounds didox (DX; 3,4-dihydroxybenzohydroxamic acid; 350 mg/kg/day) and trimidox (TX; 3,4,5-trihydroxybenzamidoxime; 175 mg/kg/day) in the murine AIDS (LPBM5 MuLV) model of retrovirus infection. Infected mice received daily drug treatment for 8 weeks. Efficacy was determined by measuring drug effects on retroviral-induced disease progression (i.e. development of splenomegaly and hypergammaglobulinemia) and by evaluating splenic levels of proviral DNA. Bone marrow toxicity was evaluated by measuring peripheral blood indices (WBC, hematocrit and reticulocyte counts), femoral cellularity and by determining the numbers of hematopoietic progenitor cells (CFU-GM, BFU-E) per femur and spleen. Compared to infected controls receiving no drug treatment, disease progression was significantly suppressed by TX, DX and HU. However, HU was associated with mortality and induced significant hematopoietic toxicity in a time- and dose-dependent manner. Conversely, TX and DX effectively inhibited retrovirus-induced disease but did not induce hematopoietic toxicity. These results suggest that due to their reduced hematopoietic toxicity and ability to inhibit disease progression in murine AIDS, TX and DX may offer effective alternatives to HU therapy in HIV-1 infection.