Evolutionary conservation and over-representation of functionally enriched network patterns in the yeast regulatory network

Background  

Localized network patterns are assumed to represent an optimal design principle in different biological networks. A widely used method for identifying functional components in biological networks is looking for network motifs – over-represented network patterns. A number of recent studies have undermined the claim that these over-represented patterns are indicative of optimal design principles and question whether localized network patterns are indeed of functional significance. This paper examines the functional significance of regulatory network patterns via their biological annotation and evolutionary conservation.     

On the mechanisms of neuroprotection by creatine and phosphocreatine

Creatine and phosphocreatine were evaluated for their ability to prevent death of cultured striatal and hippocampal neurons exposed to either glutamate or 3-nitropropionic acid (3NP) and to inhibit the mitochondrial permeability transition in CNS mitochondria. Phosphocreatine (PCr), and to a lesser extent creatine (Cr), but not (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), dose-dependently ameliorated 3NP toxicity when applied simultaneously with the 3NP in Mg2+-free media. Pre-treatment of PCr for 2 or 5 days and Cr for 5 days protected against glutamate excitotoxicity equivalent to that achieved by MK801 post-treatment. The combination of PCr or Cr pre-treatment and MK801 post-treatment did not provide additional protection, indicating that both prevented the toxicity attributable to secondary glutamate release. To determine if Cr or PCr directly inhibited the permeability transition, mitochondrial swelling and depolarization were assayed in isolated, purified brain mitochondria. PCr reduced the amount of swelling induced by calcium by 20%. Cr decreased mitochondrial swelling when inhibitors of creatine kinase octamer-dimer transition were present. However, in brain mitochondria prepared from rats fed a diet supplemented with 2% creatine for 2 weeks, the extent of calcium-induced mitochondrial swelling was not altered. Thus, the neuroprotective properties of PCr and Cr may reflect enhancement of cytoplasmic high-energy phosphates but not permeability transition inhibition.     

New evidence for hominid presence in the Lower Pleistocene of the Southern Levant

The site of 'Ubeidiya is located in the Jordan Valley, Israel and has been biochronologically dated to 1.5 m.y.a. It exhibits large lithic and faunal assemblages. Previous published hominid material includes a molar (UB 1701) and I(2) (UB 1700). A recent review of the faunal material from previous excavations has revealed a highly worn hominid right lateral lower incisor (UB 335). The tooth was found in situ in the Lower Pleistocene deposits of stratum I-26a, which is comprised of sand and conglomerates of flint, limestone and basalt indicative of a pebbled lakeshore environment. Taphonomic analysis of the macromammal assemblage indicates high-energy fluvial transport. Paleoecological reconstruction suggests a large woodland fauna with a small percent of open steppe species.UB 335 did not differ significantly from the Lower Pleistocene hominid and modern populations but did differ significantly from all other fossil populations. Two-tailed Student t -test and single classification Model II ANOVA of the buccolingual diameter did not distinguish between Lower Pleistocene species: Homo habilis, H. ergaster and H. cf. erectus. Thus, UB 335 can be identified as a Lower Pleistocene hominid although it cannot be securely assigned to any particular species within that time frame. The current date of the 'Ubeidiya deposits and the location of the site within the Levantine corridor suggests a tenative identification as H. ergaster.     

Unlocking the secrets of syndecans: transgenic organisms as a potential key

Heparan sulfate proteoglycans are known to modulate the activity of a large number of extracellular ligands thereby having the potential to regulate a great diversity of biological processes. The long-term studies in our laboratory have focused on the syndecans, one of the major cell surface heparan sulfate proteoglycan families. Most early work on syndecans involved biochemical studies that provided initial information on their structure and putative biological roles. In recent years, the development of transgenic organisms has allowed a more complete understanding of syndecan function. Studies with transgenic syndecan-1 and syndecan-3 mice have demonstrated an unforeseen role for syndecans in the regulation of feeding behavior. Syndecan-1 knockout mice display a reduced susceptibility to both Wnt-induced tumorigenesis and microbial pathogenesis. Experiments with Drosophila show that syndecan is first expressed upon cellularization in the early embryo, and may play a role in the early developmental stages of the fly. This review focuses on these diverse functions of the syndecans that have been elucidated by the use of transgenic mice and Drosophila as model systems. Published in 2003.     

Scavenging of reactive oxygen species by a novel glucurinated flavonoid antioxidant isolated and purified from spinach

NAO is a natural water soluble antioxidant that was isolated and purified from spinach leaves. Using HPLC, NMR, and CMR spectroscopy, the main components were identified as flavonoids and p-coumaric acid derivatives. The NAO was found to be a very effective antioxidant in several in vivo and in vitro biological systems. In the present study, the antioxidant activity of the novel antioxidant glucurinated flavonoid (GF) isolated and characterized from NAO, is compared to well-known antioxidants. In addition, the direct free radical scavenging properties of the purified component GF were studied using the electron spin resonance (ESR) technique. GF and NAO were found to be superior to EGCG and NAC and to the Vitamin E homologue Trolox in inhibiting reactive oxygen species (ROS) formation in the autooxidation system of linoleic acid and in fibroblasts exposed to metal oxidation. GF and NAO were found to inhibit the ESR signal intensity of DMPO-O(2) radical formation during the riboflavin photodynamic reaction. 10 mM GF caused approximately 90% inhibition in the intensity of the ESR signal, while NAO at a concentration of 60 microg/ml caused an inhibition of about 50%. Using the Fenton reaction, GF and NAO were found to inhibit DMPO-OH radical formation. A concentration of 2 mM GF caused a 70% inhibition in the intensity of the DMPO-OH radical ESR signal, while propyl gallate at the same concentration caused only 50% inhibition. Furthermore, both GF and NAO also inhibited the (1)O(2) dependent TEMPO radical generated in the photoradiation TPPS4 system. About 80% inhibition was obtained by 4 mM GF. The results obtained indicate that the natural antioxidants derived from spinach may directly affect the scavenging of ROS and, as a consequence, may be considered as effective sources for combating oxidative damage.