Orbital history and seasonality of regional precipitation

The Arizona monsoon, a major source of precipitation in the Southwest, shares many features with the monsoons of other continents. Computer modeling and fossil data indicate maximum extent of the African and Asian monsoons 9000 years ago. Fossil data indicate increased summer precipitation 9000 years ago, synchronous with the maxima of the African and Asian monsoons and, paradoxically, with the early-Holocene xerothermic of the Pacific Northwest. Climate model runs for 6000, 9000, 11,500, 13,000, and 18,000 years ago indicate increased summer precipitation 9000 years ago and a reciprocal relationship between precipitation in the Northwest and Southwest, but they relegate insolation to a role secondary to the North American ice sheet in regulating climate, and suggest a non-monsoon source for much of the summer precipitation in the Southwest prior to 9000 years ago.     

A Statistical Review of Carcinoma of the Lip

Among 3166 patients with microscopically confirmed squamous cell carcinoma of the lip registered at The Ontario Cancer Treatment and Research Foundation''s Regional Clinics in 1938-1955, the five-year crude survival rate was 65%, and the five-year net survival rate 89%. Survival was influenced by age, site and size of primary lesion, local and regional invasion, long delay, and treatment method. The initial treatment appeared to control the primary lesion in 84% of cases and involved lymph nodes in 58%. The net survival rates improved over the survey period. Findings confirm the usefulness of the proposed TNM staging.     

Loop 2 of limulus myosin III is phosphorylated by protein kinase A and autophosphorylation

Little is known about the functions of class III unconventional myosins although, with an N-terminal kinase domain, they are potentially both signaling and motor proteins. Limulus myosin III is particularly interesting because it is a phosphoprotein abundant in photoreceptors that becomes more heavily phosphorylated at night by protein kinase A. This enhanced nighttime phosphorylation occurs in response to signals from an endogenous circadian clock and correlates with dramatic changes in photoreceptor structure and function. We seek to understand the role of Limulus myosin III and its phosphorylation in photoreceptors. Here we determined the sites that become phosphorylated in Limulus myosin III and investigated its kinase, actin binding, and myosin ATPase activities. We show that Limulus myosin III exhibits kinase activity and that a major site for both protein kinase A and autophosphorylation is located within loop 2 of the myosin domain, an important actin binding region. We also identify the phosphorylation of an additional protein kinase A and autophosphorylation site near loop 2, and a predicted phosphorylation site within loop 2. We show that the kinase domain of Limulus myosin III shares some pharmacological properties with protein kinase A, and that it is a potential opsin kinase. Finally, we demonstrate that Limulus myosin III binds actin but lacks ATPase activity. We conclude that Limulus myosin III is an actin-binding and signaling protein and speculate that interactions between actin and Limulus myosin III are regulated by both second messenger mediated phosphorylation and autophosphorylation of its myosin domain within and near loop 2.     

Increase in levels of microbiota recoverable from male and larval Myrmecia gulosa (Fabricius) (Hymenoptera: Formicidae) following segregation from worker ants

The segregation of laboratory maintained male and larval Myrmecia gulosa from workers resulted in increased levels of culturable microbiota. After 29 days, microbial levels recovered from segregated males and larvae were 27 and 126 times greater than from males and larvae not segregated from workers. These findings are consistent with the hypothesis that metapleural gland secretions, absent in larvae and males, are transferred from workers to larvae, and males contribute to the inhibition of cuticular microbiota.     

Variations in serum dopamine beta-hydroxylase in normal subjects and chronic alcoholics

Serum dopamine beta-hydroxylase (DBH) activity varies greatly between individuals but is usually relatively constant within individuals. DBH activity was determined in 20 normal subjects and 6 chronic alcoholics during alcohol ingestion and withdrawal, under controlled and standardized conditions. For all subjects mean random DBH was 423 +/- 249 (mean +/- SD) nmol phenylethanolamine/h per millilitre serum. Between-day serum DBH values vary more than within-day values (21.1% vs 15.1%). Cold-pressor testing or sudden standing does not increase mean DBH; however, some individuals show a significant increase which cannot be elicited on repeat testing. Mean DBH activity did not vary significantly over 24 h. Clinically useful correlations between single random DBH and blood pressure or 24-h urine catechols should not be expected.     

Regulation of myosin 5a and myosin 7a

The myosin superfamily is diverse in its structure, kinetic mechanisms and cellular function. The enzymatic activities of most myosins are regulated by some means such as Ca2+ ion binding, phosphorylation or binding of other proteins. In the present review, we discuss the structural basis for the regulation of mammalian myosin 5a and Drosophila myosin 7a. We show that, although both myosins have a folded inactive state in which domains in the myosin tail interact with the motor domain, the details of the regulation of these two myosins differ greatly.     

Phosphorylation-dependent regulation of Limulus myosin

Myosin from Limulus, the horseshoe crab, is shown to be regulated by a calcium-calmodulin-dependent phosphorylation of its regulatory light chains. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of a Limulus myosin preparation reveals three light chain bands. Two of these light chains have been termed regulatory light chains based on their ability to bind to light chain-denuded scallop myofibrils (Sellers, J. R., Chantler, P. D., and Szent-Gy?rgyi, A. G. (1980) J. Mol. Biol. 144, 223-245). Ths other light chain does not bind to these myofibrils and is thus termed the essential light chain. Both Limulus regulatory light chains can be phosphorylated with a highly purified turkey gizzard myosin light chain kinase or with a partially purified myosin light chain kinase which can be isolated from Limulus muscle by affinity chromatography on a calmodulin-Sepharose column. Phosphorylation with both of these enzymes requires calcium and calmodulin. Limulus myosin is isolated in an unphosphorylated form. The MgATPase of this unphosphorylated myosin is only slightly activated by rabbit skeletal muscle actin plus tropomyosin. The calcium-dependent phosphorylation of the myosin results in an increase in the actin-activated MgATPase rate. Once phosphorylated, the actin-activated MgATPase rate is only slightly modified by calcium. This suggests that calcium operates mainly at the level of the myosin kinase-calmodulin system.     

Hypercholesterolemia boosts joint destruction in chronic arthritis. An experimental model aggravated by foam macrophage infiltration

Objective

The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.

Methods

Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-α and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone.

Results

Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-α and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups.

Conclusions

This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process.     

Early therapy evaluation of combined cetuximab and irinotecan in orthotopic pancreatic tumor xenografts by dynamic contrast-enhanced magnetic resonance imaging

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n = 6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p = .050), microvessel densities (p = .002), and proliferating cell densities (p = .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.