Şerefköy-2, a new Late Miocene mammal locality from the Yatağan Formation,Muğla,SW Turkey

Here we report on a new fossil locality, ?erefköy-2, from the Yata?an Basin of southwestern Turkey that preserves a well-sampled, abundant, and diverse mammal fauna. Indeed, after three field seasons, more than 1200 catalogued specimens representing 26 mammal species belonging to 14 genera make the ?erefköy-2 mammalian assemblage one of the richest Late Miocene fauna from Anatolia. Five hipparionines, six bovids, including the rare and enigmatic Urmiatherium rugosifrons and the presence of Pliohyrax graecus, strongly support affinities with Late Miocene faunas from Samos Island, Greece. Through a consideration of the identified material and the subsequent comparison with material from well-known Balkan and Anatolian faunas, a Middle Turolian (MN12) age for ?erefköy-2 is indicated.     

Hydrogen Peroxide-Induced Inhibition of Vasomotor Activity: Evaluation of Single and Combined Treatments With Vitamin A and Insulin in Streptozotocin-Diabetic Rats

A positive correlation has been established between increased oxidative stress and cardiovascular diseases in diabetes mellitus. We evaluated the effects of single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for 12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor activity, oxidative stress and retinol metabolism in 12-week streptozotocin diabetic rats. The vasomotor activity was determined by measuring in vitro responsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in the absence or in the presence of hydrogen peroxide (H₂O₂). Preincubation with H₂O₂ (10 μM) produced a significant decrease in PE (1 mM)-induced contraction in untreated-diabetic but not in control rats. Single treatment with insulin counteracted this effect of H₂O₂ and also reversed the increased contractile response of diabetic aorta to PE, while vitamin A was found to be ineffective. H₂O₂ (10 μM) also inhibited ACh (1 mM)-stimulated endothelium- dependent relaxation two fold more in diabetic than in control aorta. In the prevention of H₂O₂-induced inhibition of vascular relaxation to ACh, vitamin A alone was markedly effective while insulin alone was not. The combination of vitamin A plus insulin removed the inhibitory action of H₂O₂ in diabetic aorta. Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance (TBARS) in association with decreased levels of plasma retinol and retinol-binding protein (RBP). Single treatment with insulin, in spite of allowing recovery of normal growth rate and improved glucose and retinol metabolism in diabetic rats, was unable to control TBARS production to the same extent as vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated endothelium-dependent vasorelaxant tone in normal physiological levels depends largely on the prevention and/or inhibition of peroxidative stress, which is achieved by combined treatment with vitamin A plus insulin. The use of vitamin A together with insulin provides a better metabolic control and more benefits than use of insulin alone in the reduction of diabetes-induced vascular complications.     

Production of l-aspartic acid by biotransformation and recovery using reverse micelle and gas hydrate methods

l-Aspartic acid (l-Asp) was produced using Escherichia coli (ATCC 11303), and its recovery from the reaction mixture was studied using reverse micelle and gas hydrate methods. The effect of initial substrate concentration on l-Asp production was also investigated, and inhibition was shown to occur above 0.75 mol L^?1. The values of the kinetic constants were determined as r_max=2.33×10^?4 mol L^?1 min^?1, K_M=0.19 mol L^?1, and K_ss=3.98 mol L^?1. The reverse micelle phase used for extraction contained Aliquat-336, 1-decanol and isooctane, and a micro-injection technique was used for extraction of l-Asp. The reverse micelle system is a useful technique for obtaining small particle sizes, which can be used for the synthesis of nanoparticle biomolecules. Recovery of l-Asp from reverse micelles using CO₂ hydrates was carried out, giving a recovery of 55%. The formation of CO₂ hydrate from the reverse micelle solution breaks the micelle by reducing the amount of water in the micelle structure, thus precipitating the l-Asp.     

New carnivoran remains from the Late Miocene of Turkey

A great number of carnivoran remains from various late Miocene localities of Turkey, housed in the Natural History Museum of Aegean University, Bornova-Izmir, are described and compared with those from Eurasian localities for their determination. Thirteen different taxa were determined and some of them are recognized for the first time in Turkey or in their localities. Noteworthy is the presence of Dinocrocuta gigantea, which was recognized for the first time in Turkey, found in the early Vallesian locality Bayraktepe II, and the presence of the otter Sivaonyx hessicus which is a rare taxon in Eurasia, known from Eppelsheim, Germany and from Küçükçekmece and Bayraktepe II, Turkey. The hyaenid Adcrocuta cf. eximia was recognized for the first time in the Vallesian of Middle Sinap. The new determined carnivoran taxa provided some biochronological information which helps to date the localities or confirm their age.     

The effects of chronic trimetazidine treatment on mechanical function and fatty acid oxidation in diabetic rat hearts

Clinical and experimental evidence suggest that increased rates of fatty acid oxidation in the myocardium result in impaired contractile function in both normal and diabetic hearts. Glucose utilization is decreased in type 1 diabetes, and fatty acid oxidation dominates for energy production at the expense of an increase in oxygen requirement. The objective of this study was to examine the effect of chronic treatment with trimetazidine (TMZ) on cardiac mechanical function and fatty acid oxidation in streptozocin (STZ)-diabetic rats. Spontaneously beating hearts from male Sprague-Dawley rats were subjected to a 60-minute aerobic perfusion period with a recirculating Krebs-Henseleit solution containing 11 mmol/L glucose, 100 muU/mL insulin, and 0.8 mmol/L palmitate prebound to 3% bovine serum albumin (BSA). Mechanical function of the hearts, as cardiac output x heart rate (in (mL/min).(beats/min).10-2), was deteriorated in diabetic (73 +/- 4) and TMZ-treated diabetic (61 +/- 7) groups compared with control (119 +/- 3) and TMZ-treated controls (131 +/- 6). TMZ treatment increased coronary flow in TMZ-treated control (23 +/- 1 mL/min) hearts compared with untreated controls (18 +/- 1 mL/min). The mRNA expression of 3-ketoacyl-CoA thiolase (3-KAT) was increased in diabetic hearts. The inhibitory effect of TMZ on fatty acid oxidation was not detected at 0.8 mmol/L palmitate in the perfusate. Addition of 1 mumol/L TMZ 30 min into the perfusion did not affect fatty acid oxidation rates, cardiac work, or coronary flow. Our results suggest that higher expression of 3-KAT in diabetic rats might require increased concentrations of TMZ for the inhibitory effect on fatty acid oxidation. A detailed kinetic analysis of 3-KAT using different concentrations of fatty acid will determine the fatty acid inhibitory concentration of TMZ in diabetic state where plasma fatty acid levels are increased.     

14-3-3 binding to the IGF-1 receptor is mediated by serine autophosphorylation

The phosphoserine-binding 14-3-3 proteins have been implicated in playing a role in mitogenic and apoptotic signaling pathways. Binding of 14-3-3 proteins to phosphoserine residues in the C-terminus of the insulin-like growth factor-1 receptor (IGF-1R) has been described to occur in a variety of cell systems, but the kinase responsible for this serine phosphorylation has not been identified yet. Here we present evidence that the isolated dimeric insulin-like growth factor-1 receptor kinase domain (IGFKD) contains a dual specific (i.e. tyrosine/serine) kinase activity that mediates autophosphorylation of C-terminal serine residues in the enzyme. From the total phosphate incorporation of approximately 4 mol per mol kinase subunit, 1 mol accounts for serine phosphate. However, tyrosine autophosphorylation proceeds more rapidly than autophosphorylation of serine residues (t(1/2) approximately 1 min vs. t(1/2) approximately 5 min). Moreover, dot-blot and far-Western analyses reveal that serine autophosphorylation of IGFKD is sufficient to promote binding of 14-3-3 proteins in vitro. The proof that dual kinase activity of IGFKD is necessary and sufficient for 14-3-3 binding was obtained with an inactive kinase mutant that was phosphorylated on serine residues in a stoichiometric reaction with the catalytically active enzyme. Thus, the IGF-1R itself might be responsible for the serine autophosphorylation which leads to recognition of 14-3-3 proteins in vivo.