Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

Resprouting as a key functional trait: how buds, protection and resources drive persistence after fire.

Resprouting as a response to disturbance is now widely recognized as a key functional trait among woody plants and as the basis for the persistence niche. However, the underlying mechanisms that define resprouting responses to disturbance are poorly conceptualized. Resprouting ability is constrained by the interaction of the disturbance regime that depletes the buds and resources needed to fund resprouting, and the environment that drives growth and resource allocation. We develop a buds-protection-resources (BPR) framework for understanding resprouting in fire-prone ecosystems, based on bud bank location, bud protection, and how buds are resourced. Using this framework we go beyond earlier emphases on basal resprouting and highlight the importance of apical, epicormic and below-ground resprouting to the persistence niche. The BPR framework provides insights into: resprouting typologies that include both fire resisters (i.e. survive fire but do not resprout) and fire resprouters; the methods by which buds escape fire effects, such as thick bark; and the predictability of community assembly of resprouting types in relation to site productivity, disturbance regime and competition. Furthermore, predicting the consequences of global change is enhanced by the BPR framework because it potentially forecasts the retention or loss of above-ground biomass.

Grass species with smoke-released seed dormancy: A response to climate and fire regime but not photosynthetic pathway.

Both C3 and C4 photosynthetic pathways and smoke-released seed dormancy occur among grasses. C4 species evolved from C3 species as seasonality and fire frequency increased and might therefore imply that their smoke sensitivity increased. I searched the worldwide literature for reports on germination responses among grasses, whose photosynthetic pathway was known, to treatment by smoke. Data were obtained for 217 species and 126 genera. While subfamilies tended to be C3 (Pooideae), C4 (Chloridoideae) or a mixture (Panicoideae), a beneficial smoke response was independent of their photosynthetic pathway. The only exceptions were Danthonioideae (C3, non-smoke responsive) and Triodia (C4, smoke responsive). One third of both C3 and C4 genera were smoke responsive. Even within genera, 90% of species showed contrasting smoke responses, confirming that smoke sensitivity is rarely taxonomically constrained. Data on photosynthetic pathway, climate, fire regime and vegetation were compiled for 15 regions that formed four distinct groups: 1) In warm climates with aseasonal rainfall, C4 grasses are moderately better represented, with crown fires and limited smoke responses. 2) In cool regions, most species are C3, with surface-crown fires and lack smoke responses. 3) In warm regions with summer rain (savannas), most species are C4, with surface fires and lack smoke responses. 4) In Mediterranean-climate regions with summer drought, most species are C3, with crown fires and smoke-released dormancy. Thus, even though C3 and C4 grasses are equally capable of expressing smoke sensitivity, their response depends on the region's climate and fire regime that also dictate which photosynthetic pathway dominates.

Seed biologists beware: Estimates of initial viability based on ungerminated seeds at the end of an experiment may be error-prone.

Seed viability is routinely measured on seeds that fail to germinate at the end of an experiment. Together with the number of germinants, this is used to estimate viability of the seeds at start of the experiment (i.e., initial viability) and provides the comparative basis on which germination success is determined. The literature and recent data on the germination requirements of Leucadendron species were examined to determine if there was any evidence for a treatment effect on viability of ungerminated seeds at the end of the experiment. The survey showed that sometimes (perhaps often, as the problem has yet to be recognized or reported) prolonged duration in the treatment, especially the control where little germination occurs, lead to loss of viability during the experiment. This resulted in underestimation of initial viability if that treatment was used. I caution against the routine use of end-of-trial germination and viability of ungerminated seeds as an estimate of initial viability in determining germination success of various treatments. I explore ways to deal with the problem but the preference is for estimates of initial viability to be undertaken on a separate sample of seeds concurrently with the experiment as this avoids the risk of seed death during the trial.

Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice.

AIMS/HYPOTHESIS: Metformin is widely used for the treatment of type 2 diabetes. Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1). We examined whether metformin exerts glucoregulatory actions via modulation of the incretin axis. METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparα (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39). Experimental endpoints included glucose tolerance, plasma insulin levels, gastric emptying and food intake. Incretin receptor expression was assessed in isolated islets from metformin-treated wild-type and Pparα(-/-) mice, and in INS-1 832/3 beta cells with or without peroxisome proliferator-activated receptor (PPAR)-α or AMP-activated protein kinase (AMPK) antagonists. RESULTS: In wild-type mice, metformin acutely increased plasma levels of GLP-1, but not those of gastric inhibitory polypeptide or peptide YY; it also improved oral glucose tolerance and reduced gastric emptying. Metformin significantly improved oral glucose tolerance despite loss of incretin action in Glp1r(-/-), Gipr(-/-) and Glp1r(-/-) :Gipr(-/-) mice, and in wild-type mice fed a high-fat diet and treated with exendin(9-39). Levels of mRNA transcripts for Glp1r, Gipr and Pparα were significantly increased in islets from metformin-treated mice. Metformin directly increased Glp1r expression in INS-1 beta cells via a PPAR-α-dependent, AMPK-independent mechanism. Metformin failed to induce incretin receptor gene expression in islets from Pparα(-/-) mice. CONCLUSIONS/INTERPRETATION: As metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-α, metformin may be mechanistically well suited for combination with incretin-based therapies.

Contrasting impacts of pollen and seed dispersal on spatial genetic structure in the bird-pollinated Banksia hookeriana.

In plants, pollen- and seed-dispersal distributions are characteristically leptokurtic, with significant consequences for spatial genetic structure and nearest-neighbour mating. However, most studies to date have been on wind- or insect-pollinated species. Here, we assigned paternity to quantify effective pollen dispersal over 9 years of mating, contrasted this to seed dispersal and examined their effects on fine-scale spatial genetic structure, within the bird-pollinated shrub Banksia hookeriana (Proteaceae). We used 163 polymorphic amplified fragment length polymorphism markers to assess genetic structure and pollen dispersal in a spatially discrete population of 112 plants covering 0.56 ha. Spatial autocorrelation analysis detected spatial genetic structure in the smallest distance class of 0-5 m (r=0.025), with no significant structure beyond 8 m. Experimentally quantified seed-dispersal distances for 337 seedlings showed a leptokurtic distribution around a median of 5 m, reaching a distance of 36 m. In marked contrast, patterns of pollen dispersal for 274 seeds departed strikingly from typical near-neighbour pollination, with a distribution largely corresponding to the spatial distribution of plants. We found very high multiple paternity, very low correlated paternity and an equal probability of siring for the 50 closest potential mates. Extensive pollen carryover was demonstrated by multiple siring in 83 of 86 (96.5%) two-seeded fruits. Highly mobile nectar-feeding birds facilitate this promiscuity through observed movements that were effectively random. As the incidence of bird-pollination is markedly greater in the Southwest Australian Floristic Region than elsewhere, our results have broad and novel significance for the evolution and conservation for many species in Gondwanan lineages.

A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or ß-cell mass in NZO mice.

BACKGROUND/OBJECTIVES: Dietary guidelines for the past 20 years have recommended that dietary fat should be minimized. In contrast, recent studies have suggested that there could be some potential benefits for reducing carbohydrate intake in favor of increased fat. It has also been suggested that low-carbohydrate diets be recommended for people with type 2 diabetes. However, whether such diets can improve glycemic control will likely depend on their ability to improve ß-cell function, which has not been studied. The objective of the study was to assess whether a low-carbohydrate and therefore high-fat diet (LCHFD) is beneficial for improving the endogenous insulin secretory response to glucose in prediabetic New Zealand Obese (NZO) mice. METHODS: NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic ß-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. ß-Cell mass was assessed in histological sections of pancreata collected at the end of the study. RESULTS: In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was ß-cell mass (P=0.75). CONCLUSIONS: An LCHFD is unlikely to be of benefit for preventing the decline in ß-cell function associated with the progression of hyperglycemia in type 2 diabetes.

Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine.

Analogues of the renin octapeptide substrate were synthesized in which replacement of the scissile dipeptide with (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta) transformed the substrate sequence into potent, transition-state analogue, competitive inhibitors of renin. Synthesis and incorporation of the cyclohexylalanyl analogue of Sta, (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA), gave the most potent inhibitors of renin yet reported, including N-isovaleryl-L-histidyl-L-prolyl-L-phenylalanyl-L-histidyl-ACHPA-L -leucyl-L- phenylalanyl amide [Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2,3], with renin inhibitions of Ki = 1.6 X 10(-10) M (human kidney renin), IC50 = 1.7 X 10(-10)M (human plasma renin), IC50 = 1.9 X 10(-9)M (dog plasma renin), and IC50 = 2.1 X 10(-8) M (rat plasma renin). This inhibitor 3, containing ACHPA, was 55-76 times more potent vs. human renin than the comparable Sta-containing inhibitor 1 and 17 times more potent vs. dog renin than 1. Inhibitor 3 lowered blood pressure in sodium-deficient dogs, with in vivo potency 19 times that shown by 1, in close agreement with the relative in vitro potencies. Structure-activity results are presented that show the minimal N-terminus for these inhibitors. An ACHPA-containing pentapeptide, N-[(ethyloxy)carbonyl]-L-phenylalanyl-L- histidyl-ACHPA-L-leucyl-L-phenylalanyl amide [Etoc-Phe-His-ACHPA-Leu-Phe-NH2,8], retained subnanomolar inhibitory potency. Molecular modelling studies are described that suggested the design of ACHPA.

Renin inhibitors containing hydrophilic groups. Tetrapeptides with enhanced aqueous solubility and nanomolar potency.

Nineteen tetrapeptides containing statine (Sta) and 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) were prepared. Solubility measurements of these compounds were carried out in H2O and in pH 7.4 phosphate buffer solution, and their partition coefficients were determined in a 1:1 1-octanol/sodium phosphate-citric acid buffer system. The tetrapeptides were tested in vitro for their ability to inhibit porcine, canine, and human plasma renins. Four compounds, 6, 12, 14, and 20, were potent inhibitors against all renins tested (IC50 = 10(-9) M). Compound 12 was administered orally to dogs and substantially inhibited plasma renin activity for up to 5 h. The addition of polar groups to the C-terminus of Sta- and ACHPA-containing tetrapeptides renders them soluble in aqueous milieu and provides a valuable tool with which to examine the role of the renin-angiotensin system in physiological and pathological circumstances.

Renin inhibitors. Statine-containing tetrapeptides with varied hydrophobic carboxy termini.

A series of statine-containing tetrapeptides, systematically modified at the carboxy terminus with various hydrophobic aromatic groups, is described. These compounds were tested in vitro for their ability to inhibit porcine, human plasma, and purified human kidney renins. These analogues help to define optimal binding aspects in a region of the enzyme that appears to be specific for spatial arrangement of aromatic groups. Replacement of the metabolically labile Phe amide with nonpeptidal groups proved possible while achieving inhibitory potency in the nanomolar range vs. porcine kidney renin. For the compounds 6i, 6m, and 6o, a large discrepancy in potency between the human plasma and the purified human kidney renin assays was observed. This disparity does not appear to be a consequence of a previously proposed plasma binding component.

Porter's generic strategies, discontinuous environments, and performance: a longitudinal study of changing strategies in the hospital industry.

OBJECTIVE: Changes in generic strategies in response to discontinuous environments have been relatively ignored in the management literature. This study reports an examination of the relationships between Porter's (1980) generic strategies, discontinuous environments, and performance. DATA SOURCES: Archival data for 1984 and 1988 were collected for 172 acute care hospitals in Florida in order to test these relationships. STUDY DESIGN: To examine fully the performance impact of changes in strategy in a discontinuous environment, a longitudinal research design that identified a firm's strategy at two points in time, 1984 and 1988, was used. PRINCIPAL FINDINGS: Results indicate that firms with a proper strategy environment fit performed the highest, firms that did not change their strategy had no change in performance, and firms that changed their strategy toward a proper strategy environment showed an increase in performance. CONCLUSION: Findings support the notion that hospitals with appropriate strategy-environment combinations will exhibit higher performance.

Bronchodilators and diuretics in children with bronchopulmonary dysplasia.

Pulmonary function tests (PFT) were obtained during the course of a self-controlled study of six children aged 5 to 43 months who had moderate to severe bronchopulmonary dysplasia (BPD). Changes after the administration of intravenous (IV) furosemide (2 mg/kg), inhaled isoproterenol (0.2 cc, 1:200), inhaled atropine sulfate (0.05 mg/kg), and a placebo were assessed. The study indicated the furosemide and atropine significantly (P less than 0.05) increased dynamic compliance (CL) for the group. A decrease in total pulmonary resistance (RL) and work of breathing (W) was observed after isoproterenol, although the responses were not significant (P = 0.08 and P = 0.09, respectively). It was speculated that pulmonary edema and increased vagal tone may contribute to small airway dysfunction in children who have BPD.

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis.

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.

The diagnostic and treatment approach to two common conditions by the physician members of a community health maintenance organization.

We retrospectively collected data from one community managed care organization on all ambulatory care patients initially diagnosed with pneumonia or acute bronchitis from October, 1, 1992, to March 31, 1993, and from November 1, 1993, to January 31, 1994. We considered treatment to be successful when patients did not return for any related service within 15 days of initial diagnosis. We identified 2,490 episodes of illness, 85.7% which were acute bronchitis and 14.3% which were pneumonia. Overwhelmingly, physicians approached these conditions empirically (no diagnostic test); just 8.6% of patients had a diagnostic test during the 15-day episode of illness. Two-hundred twenty-nine of the episodes (9.2%) were apparently related to initial diagnoses, as they occurred during the 15-day period. More branded prescriptions (vs. generic) were dispensed during these related episodes. One patient was hospitalized and 19 patients used the emergency room either for first or subsequent visits. Empiric treatment is associated with effective diagnosis and therapy in ambulatory care patients with acute bronchitis and pneumonia. It remains unclear, however, if this strategy is the most cost-effective or if it leads to the most effective utilization of services.

Milk-of-calcium renal cyst, evaluated by ultrasound and computed tomography.

Milk-of-calcium renal cysts, which when asymptomatic need no treatment, sometimes pose diagnostic problems by conventional radiography. Two such cases are here reported. The first case was further evaluated by ultrasonography only, the second case also by computed tomography and cyst puncture, because of an irregularity in the cyst wall. Both imaging modalities added valuable information.

Isolation and characterisation of an antifungal antibiotic (GR135402) with protein synthesis inhibition.

A novel antifungal antibiotic GR135402 has been isolated from a fermentation broth of Graphium putredinis which inhibited protein synthesis in Candida albicans but not rabbit reticulocytes. The spectrum of activity included C. albicans and Cryptococcus neoformans but not some other Candida species or Aspergillus species. Therapeutic efficacy in a mouse model of systemic candidosis was attained following parenteral dosing.

The intracellular metabolism of iodine in carcinogenesis.

Research from this laboratory and others have concluded that significant glandular atypia, and often neoplasia, occurs in the breast tissues of rodents and humans under conditions of iodine deprivation. These cellular changes caused by iodine deficiency are intensified, by aging, steroid hormones, and pituitary hormones. There has been controversy concerning the effect of iodine deficiency on stimulation and maintenance of cancer of the breast in rodents when the cancer is induced chemically or by transplantation. However, neither within this induced neoplastic framework nor with the dysplastic changes seen by deficiency alone have laboratory studies of thepathway of intracellular iodine been previously possible.The new research data addresses the question of whether organification occurs and whether iodine significantly affects the intracellular structures. An hypothesis will be presented that places the inorganic element, iodine, into association with receptor protein complexes that may be responsible for intracellular sex hormone activity. The relationship of this mechanism to carcinogenesis in breast tissue will be considered.

Seed dormancy, after-ripening and light requirements of four annual Asteraceae in south-western Australia.

The role of dormancy, temperature and light in the regulation of seed germination of four annual Asteraceae from south-western Australia was investigated. The experiments aimed to identify after-ripening patterns, and to relate these to climatic conditions of the habitat in which the species occur. Seeds of all species were strongly dormant at maturity and maintained high levels of dormancy for time periods corresponding to the duration of summer in south-western Australia. Dry after-ripening was promoted best by temperatures lower than those prevailing in the dry season, although differences among storage temperatures were mostly insignificant. Germination percentages were highest at average winter temperatures (15 degrees C). A logistic model revealed significant differences in germinability among species, but not between incubation temperatures or light and dark treatments across species. Three species with seeds >0.5 mg germinated better in darkness than in light, whereas germination in darkness was almost inhibited in the species with the smallest seeds (0.14 mg). The course of dormancy loss, tested over a range of fluctuating incubation temperatures (7-30 degrees C), showed that seeds of three species came out of dormancy first at temperatures that prevail in south-western Australia during the winter (10-15 degrees C). Seeds from one species, introduced from South Africa, first lost dormancy at the lowest temperature (7 degrees C). All species showed after-ripening patterns of Type 1, typical of species growing in Mediterranean climates. The germination characteristics of the investigated species can be interpreted as ensuring that initial growth and establishment occur during the winter growing season, thereby avoiding the hot and dry summer conditions that follow seed dispersal.