Centres of diversity quantified—A maximum variance approach to a biogeographic problem

Summary A quantitative method that optimizes the mapping of species diversity in phytogeographic studies is described. Diversity is computed on the basis of species number per unit area. The optimal size of unit area for which diversity is computed is held to be that which maximises the diversity difference between species-rich and species-poor regions. An example is given using Turkish Papaver. A very high correspondence is found between intuitive insights based on long study and the computer-generated diversity maps. Phytogeographic elements were also determined by computer after gridding Turkey at the scale discovered to be optimal for diversity and scoring the grid squares for presence-absence of each species. In this case, too, quite high correspondence was found between the computer and intuitive results.Nomenclature follows Cullen (1965).The authors express their thanks to Mr. K. Roberts, University of Western Ontario Computing Centre of writing the original maximum variance program and to the National Research Council of Canada for supporting the computing side of the project.     

Alterations in osteoclast morphology following osteoprotegerin administration in the magnesium-deficient mouse

In the present study, we used osteoprotegerin (OPG), which blocks osteoclastogenesis, to correct and thus explain the hypercalcemia that is seen during dietary Mg deficiency in the mouse. Control and Mg-deficient mice received injections for 12 days of either OPG or vehicle only. Serum Ca was similar in Mg-deficient mice treated with OPG and in control mice receiving OPG (9.2±0.3 mg/dl vs. 9.2±0.5). Both groups had significantly higher serum Ca than controls or Mg-deficient animals receiving vehicle alone. Surprisingly, Mg-depleted mice that received OPG in doses that inhibit osteoclastic bone resorption remained hypercalcemic. Because mature osteoclasts still present in the marrow might be hyperactive, we examined osteoclast morphology at the light microscopic and ultrastructural level. Light microscopic examination of trabecular bone showed few osteoclasts in OPG-treated mice. Ultrastructural examination revealed that osteoclasts in OPG-treated mice have decreased contact with the endosteal bone surface and absence of a ruffled border. Because the morphology of the existing pool of mature osteoclasts did not enhance resorption, another mechanism, such as increased intestinal absorption of Ca in Mg-deficient mice, likely contributes to the hypercalcemia observed during Mg deficiency.     

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation

Introduction

Cigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis). Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We hypothesize that resolvin D1 (RvD1) has potent anti-inflammatory and pro-resolving effects in a model of cigarette smoke-induced lung inflammation.

Methods

Primary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with RvD1 in vitro, production of pro-inflammatory mediators was measured. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effects on lung inflammation and lung macrophage populations were assessed.

Results

RvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines, while upregulating the anti-inflammatory cytokine IL-10. RvD1 promoted differentiation of alternatively activated (M2) macrophages and neutrophil efferocytosis. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure.

Conclusions

RvD1 has potent anti-inflammatory and pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins have strong potential as a novel therapeutic approach to resolve lung injury caused by smoke and pulmonary toxicants.     

Methylation: a regulator of HIV-1 replication?

Pakistan, the second most populous Muslim nation in the world, has started to finally experience and confront the HIV/AIDS epidemic. The country had been relatively safe from any indigenous HIV cases for around two decades, with most of the infections being attributable to deported HIV positive migrants from the Gulf States. However, the virus finally seems to have found a home-base, as evidenced by the recent HIV outbreaks among the injection drug user community. Extremely high-risk behavior has also been documented among Hijras (sex workers) and long-distance truck drivers. The weak government response coupled with the extremely distressing social demographics of this South-Asian republic also helps to compound the problem. The time is ripe now to prepare in advance, to take the appropriate measures to curtail further spread of the disease. If this opportunity is not utilized right now, little if at all could be done later.     

Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal wound healing

Stromal-derived factor-1 (SDF-1) is a CXC chemokine that is believed to be constitutively expressed by stromal cells of numerous tissues. In this report, we demonstrate that dermal fibroblasts and vessels of noninflamed tissues express SDF-1. Unexpectedly, we found that expression of SDF-1 is regulated by inflammation. Expression of SDF-1 by primary cultures of human gingival fibroblasts is potently inhibited by activated macrophages via secretion of IL-1alpha and TNF-alpha. Levels of SDF-1 mRNA also decrease in acutely inflamed mouse dermal wounds. We propose that SDF-1 functions as a homeostatic regulator of tissue remodeling, whose expression stabilizes existing dermal architecture.     

Community water fluoridation, bone mineral density, and fractures: prospective study of effects in older women

ObjectiveTo determine whether fluoridation influences bone mineral density and fractures in older women.DesignMulticentre prospective study on risk factors for osteoporosis and fractures.SettingFour community based centres in the United States.Participants9704 ambulatory women without bilateral hip replacements enrolled during 1986-8; 7129 provided information on exposure to fluoride.ResultsWomen were classified as exposed or not exposed or having unknown exposure to fluoride for each year from 1950 to 1994. Outcomes were compared in women with continuous exposure to fluoridated water for the past 20 years (n=3218) and women with no exposure during the past 20 years (n=2563). In women with continuous exposure mean bone mineral density was 2.6% higher at the femoral neck (0.017 g/cm², P<0.001), 2.5% higher at the lumbar spine (0.022 g/cm², P<0.001), and 1.9% lower at the distal radius (0.007 g/cm², P=0.002). In women with continuous exposure the multivariable adjusted risk of hip fracture was slightly reduced (risk ratio 0.69, 95% confidence interval 0.50 to 0.96, P=0.028) as was the risk of vertebral fracture (0.73, 0.55 to 0.97, P=0.033). There was a non-significant trend toward an increased risk of wrist fracture (1.32, 1.00 to 1.71, P=0.051) and no difference in risk of humerus fracture (0.85, 0.58 to 1.23, P=0.378).ConclusionsLong term exposure to fluoridated drinking water does not increase the risk of fracture.     

Differential pathogenicity of two feline leukemia virus subgroup A molecular clones, pFRA and pF6A

F6A, a molecular clone of subgroup A feline leukemia virus (FeLV) is considered to be highly infectious but weakly pathogenic. In recent studies with a closely related subgroup A molecular clone, FRA, we demonstrated high pathogenicity and a strong propensity to undergo recombination with endogenous FeLV (enFeLV), leading to a high frequency of transition from subgroup A to A/B. The present study was undertaken to identify mechanisms of FeLV pathogenesis that might become evident by comparing the two closely related molecular clones. F6A was shown to have an infectivity similar to that of FRA when delivered as a provirus. Virus load and antibody responses were also similar, although F6A-infected cats consistently carried higher virus loads than FRA-infected cats. However, F6A-infected cats were slower to undergo de novo recombination with enFeLV and showed slower progression to disease than FRA-infected cats. Tumors collected from nine pF6A- or pFRA-inoculated cats expressed lymphocyte markers for T cells (seven tumors) and B cells (one tumor), and non-T/B cells (one tumor). One cat with an A-to-A/C conversion developed erythrocyte hypoplasia. Genomic mapping of recombinants from pF6A- and pFRA-inoculated cats revealed similar crossover sites, suggesting that the genomic makeup of the recombinants did not contribute to increased progression to neoplastic disease. From these studies, the mechanism most likely to account for the pathologic differences between F6A and FRA is the lower propensity for F6A to undergo de novo recombination with enFeLV in vivo. A lower recombination rate is predicted to slow the transition from subgroup A to A/B and slow the progression to disease.