Fructose 1,6-bisphosphatase: Dissociation of AMP cooperativity and AMP inhibition by carbamylation

Selective treatment of pig kidney fructose 1,6-bisphosphatase with potassium cyanate leads to the formation of an active carbamylated enzyme that has lost the cooperative interactions among AMP sites, but retains sensitivity to inhibition of catalytic activity by the regulator AMP. Incorporation data on [¹⁴C]KNCO indicate that the loss of enzyme cooperativity at the AMP sites is related to selective carbamylation of four lysine residues per mole of tetrameric enzyme. Exhaustive carbamylation suggests that a second lysine residue per subunit is essential for AMP inhibition.     

Inhibition of DNA alkylation damage with inorganic salts

Human exposure to alkylating agents metabolized from tobacco- and food-borne carcinogens occurs regularly. Dietary inorganic compounds such as selenium and vanadium have been shown previously to provide chemoprotective benefits in rat and human trials. Here, we present biochemical data on the ability of inorganic compounds to protect DNA from alkylation damage. An enzyme cleavage assay is used to observe alkylated DNA. Simple salts (e.g., NaCl or NiCl₂) did not prevent DNA alkylation, whereas anionic oxo species (e.g., Na₂SeO₄ or Na₃VO₄) did inhibit alkylation. We propose that these oxo species behave as nucleophilic targets for the electrophilic alkylating agents, thereby preventing DNA damage.     

Playing with bone and fat

The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine.     

The Erwin equation of biodiversity: From little steps to quantum leaps in the discovery of tropical insect diversity

Almost 40 years ago, Terry L. Erwin published a seemingly audacious proposition: There may be as many as 30 million species of insects in the world. Here, we translate Erwin's verbal argument into a diversity-ratio model—the Erwin Equation of Biodiversity—and discuss how it has inspired other biodiversity estimates. We categorize, describe the assumptions for, and summarize the most commonly used methods for calculating estimates of global biodiversity. Subsequent diversity-ratio extrapolations have incorporated parameters representing empirical insect specialization ratios, and how insect specialization changes at different spatial scales. Other approaches include macroecological diversity models and diversity curves. For many insect groups with poorly known taxonomies, diversity estimates are based on the opinions of taxonomic experts. We illustrate our current understanding of insect diversity by focusing on the six most speciose insect orders worldwide. For each order, we compiled estimates of the (a) maximum estimated number of species, (b) minimum estimated number of species, and (c) number of currently described species. By integrating these approaches and considering new information, we believe an estimate of 5.5 million species of insects in the world is much too low. New molecular methodologies (e.g., metabarcoding and NGS studies) are revealing daunting numbers of cryptic and previously undescribed species, at the same time increasing our precision but also uncertainty about present estimates. Not until technologies advance and sampling become more comprehensive, especially of tropical biotas, will we be able to make robust estimates of the total number of insect species on Earth.     

Adiponectin and ghrelin levels and body size in normoglycemic Filipino, African-American, and white women

Objective: Prior studies have reported ethnic differences in adiponectin and ghrelin, but few have assessed the role of body size in normoglycemic women. We compared fasting adiponectin and ghrelin concentrations in normoglycemic 40‐ to 80‐year‐old Filipino, African‐American, and white women. Methods: Participants included women from the Rancho Bernardo Study (n = 143), the University of California‐San Diego Filipino Women's Health Study (n = 136), and the Health Assessment Study of African‐American Women (n = 212). A 2‐hour oral glucose tolerance test was administered; glucose, insulin, lipid, and anthropometric measurements were obtained. Fasting adiponectin and ghrelin were measured by radioimmunoassay. Results: Whites and Filipinas had similar BMI (23.7 and 24.3 kg/m², respectively), waist girth (75.6 and 77.2 cm, respectively), and total body fat (27.4 and 28.5%, respectively); African‐Americans had significantly larger BMI (28.8 kg/m²), waist girth (86.3 cm), and body fat (39.6%, p < 0.0001). Adiponectin was lower in Filipinas (8.90 µg/mL) and African‐Americans (9.67 µg/mL) compared with whites (15.6 µg/mL, p < 0.001) after adjusting for age, homeostasis model assessment of insulin resistance (HOMA‐IR), and waist‐to‐hip ratio. Compared with whites, Filipinas (β = ?5.06, p < 0.0001) and African‐Americans (β = ?6.85, p < 0.0001) had significantly lower adiponectin levels after adjusting for age, waist‐to‐hip ratio, HOMA‐IR, triglycerides, high‐density lipoprotein (HDL) cholesterol, exercise, and alcohol use. Ghrelin was significantly lower in Filipinas compared with African‐Americans (1146.9 vs. 1412.2 pg/mL, p < 0.001), and this observation persisted in multivariable analysis (β = ?245.4, p < 0.0001). Ghrelin levels did not differ between whites (1356.9 pg/mL) and either ethnic group. Discussion: Normoglycemic Filipino and African‐American women had significantly lower adiponectin concentrations than white women, and Filipinas had lower ghrelin levels than African‐Americans, independently of body size or indices of insulin resistance or lipids.     

Neurotrophins,but not depolarization,regulate substance P expression in the developing optic tectum

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve‐dependent regulation of a substance P‐like immunoreactive (SP‐ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6‐cyano‐7‐nitroquinoxaline‐2,3 dione (CNQX) did not affect the percent of SP‐ir cells in the developing tectum. Treatment with d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (d‐AP‐5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) produced increases in SP‐ir cells in the treated lobes of normal animals, which were significant in the case of NT‐4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve‐transected tadpoles. These changes in the percent of SP‐ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT‐4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide‐expressing population of cells. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 131–149, 2001     

RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain

Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis.