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.     

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.     

Gas chromatographic determination of novel valproyl taurinamide derivatives in mouse and dog plasma

Valproyl taurinamides are a novel group of compounds that possess anticonvulsant activity. In this study a gas chromatographic micromethod was developed for the quantification of selected valproyl taurinamides and some of their metabolites in biological samples. Valproyl taurinamide (VTD), N-methyl valproyl taurinamide (M-VTD), N,N-dimethyl valproyl taurinamide (DM-VTD) and N-isopropyl valproyl taurinamide (I-VTD) were analyzed in mouse and dog plasma and in dog urine using gas chromatography. Flame ionization detection and mass spectrometric detection were compared. The plasma samples were prepared by solid-phase extraction using C(18) cartridges. The urine samples were prepared by liquid-liquid extraction. The sample volume used was 100 microl of dog plasma, 50 microl of mouse plasma and 20 microl of dog or mouse urine. The quantification range of the method was 1.5-50 mg/l in dog plasma (VTD only), 2.5-250 mg/l in mouse plasma (0.7-90 pmol injected) and 0.04-2 mg/ml in dog urine (VTD only). The inter-day precision in plasma and urine samples was around 10% for all quantified concentrations except LOQ (15-20%). The accuracy for all four compounds was between 90 and 110% within the entire concentration range. The developed method was suitable for quantification of a series of CNS-active valproyl taurineamide derivatives in biological samples at relevant in vivo concentrations.     

Oral cancer,cigarette smoke and mitochondrial 18 kDa translocator protein (TSPO) — In vitro,in vivo,salivary analysis

Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Δψ_m), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p < 0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133 ± 643 fmol/mg protein and 6956 ± 549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p < 0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p < 0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p < 0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p < 0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.