Modeling the Role of Negative Cooperativity in Metabolic Regulation and Homeostasis

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.     

Macromolecular synthesis in organ cultures of neonatal rat lung

Organ cultures of newborn rat lungs synthesize and accumulate DNA, RNA, collagen and noncollagenous proteins almost at a linear rate for at least 5 days. During this period the synthesis of collagen consistently exceeds the synthesis of noncollagenous proteins in a pattern similar to neonatal lung growth in vivo. Although some morphological characteristics of lung architecture are distorted after culture, fundamental structural similarities to lungs growing in intact animals are retained. When these cultures are maintained in atmospheres rich in oxygen, increased collagen synthesis is observed, a response similar to that of lungs in intact animals exposed to high oxygen concentrations in vivo. Our studies suggest that lung organ cultures may be a suitable system for investigating the biochemical aspects of lung tissue-environmental interaction. These studies were supported in parts by NIH Grant HL-19668, a contract (68-03-2005) from the U.S. Environmental Protection Agency, and grants from the California Lung Association.     

Meiofaunal responses to nutrient additions in a Mediterranean stream

1. The effects of a moderate addition of nutrients (twofold N and threefold P) were examined during a 2‐year period to determine the response to nutrient addition in a meiofaunal community inhabiting sandy patches in a Mediterranean stream. 2. The pattern of meiofaunal assemblages exhibits a high degree of intra‐ and interannual variability. This pattern alternates between periods of hydrological stability and disturbances, such as floods and droughts, which is a characteristic of Mediterranean systems. 3. A before–after–control–impact (BACI) design was used to determine the outcome of the addition by comparing an upstream non‐enriched reach with an enriched downstream reach. Analysis of the study data by means of a nonparametric permutational procedure (permanova ) showed that fertilisation had a significant effect. Density and biomass values increased in the most abundant meiofaunal groups, including microcrustaceans, oligochaetes and chironomids. Microcrustaceans were the dominant group in the permanent meiofauna. 4. We also examined differences in microcrustacean secondary production in both reaches. Ostracods and cyclopoid copepods increased their secondary production in the impacted reach as a result of the nutrient addition. 5. Our study demonstrated that moderate nutrient enrichment can affect the biomass and production of stream meiofauna, but it is still unclear whether this effect was because of autotrophic or heterotrophic pathways.     

Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.     

The Ordovician-Silurian boundary stratotype: consequences of its approval by the IUGS

Lespérance, Pierre J., Barnes, Christopher R., Berry, William B. N., Boucot, Arthur J. & Mu En-zhi 1987 07 15: The Ordovician-Silurian boundary stratotype: consequences of its approval by the IUGS.
The Ordovician-Silurian stratotype at Dob's Linn, Scotland is the second systemic boundary approved by the International Union of Geological Sciences (IUGS). A review of the internationally accepted criteria required of a stratotype shows that few of these are possessed by the Dob's Linn section. The strongest attribute of the section is the presence of zonal graptolites, although the boundary is recognized primarily on a single biological event (base of acuminatus Zone) for which the evolutionary relationships of the taxa are not established. In approving this boundary proposal in 1985, which received only simple majority support within the Ordovician-Silurian Boundary Working Group (OSBWG) and which fails to meet most of the accepted prerequisites for a stratotype, the International Commission on Stratigraphy (ICS) and the IUGS have established an unfortunate precedent. It follows that future systemic boundaries need not meet the accepted standards. It raises serious questions on the assessment and voting procedures of the International Commission on Stratigraphy and on the credence accorded the recommendations developed by the International Subcommission on Stratigraphic Classification of IUGS.     

Replication of cauliflower mosaic virus DNA in leaves and suspension culture protoplasts of cotton

Cauliflower mosaic virus (CaMV) replicated in protoplasts and in inoculated leaves of the non-host, cotton (Gossypium hirsutum, L.). Protoplasts prepared from suspension-cultured cotton cells were infected by incubation with liposome-encapsulated CaMV virions. During a 1-week culture period the amount of CaMV nucleic acid as detected by nucleic acid hybridization in the protoplasts increased significantly regardless of whether or not the protoplasts contained vacuoles. In leaves inoculated with CaMV virions or CaMV DNA, viral DNA sequences were found by leaf skeleton hybridization to be located in small circular areas. DNA extracted from ultracentrifugal pellets of homogenates of inoculated leaves contained circular, gapped CaMV DNA only when inocula contained CaMV virions, CaMV DNA, or partial nested dimer CaMV plasmid DNA. When plants had been heavily watered, the CaMV DNA recovered contained degraded CaMV DNA. The results suggest that the host range limitation for CaMV is not due to an inability to replicate or spread locally in inoculated leaves.