Estimating intrinsic structural preferences of de novo emerging random-sequence proteins: Is aggregation the main bottleneck?

Present-day proteins are believed to have evolved features to reduce the risk of aggregation. However, proteins can emerge de novo by translation of non-coding DNA segments. In this study we assess the aggregation, disorder and transmembrane propensity of protein sequences generated by translating random nucleotide sequences of varying GC-content. Potential de novo random-sequence proteins translated from regions with GC content between 40% and 60% do not show stronger aggregation propensity than existing ones and exhibit similar tendency to be disordered. We suggest that de novo emerging proteins do not mean an unavoidable aggregation threat to evolving organisms.     

CYP46 T/C Polymorphism is not Associated with Alzheimer’s Dementia in a Population from Hungary

Multiple genetic and environmental factors regulate the susceptibility to Alzheimer’s disease (AD). Recently, several independent studies have reported that a locus on chromosome 14q32.1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD. The single nucleotide polymorphism (T/C) in intron 2 of CYP46 gene has been found to confer the risk for AD. The water soluble 24(S)-hydroxysterol is the product of the CYP46A1, and elevated plasma and cerebrospinal fluid hydroxysterol concentrations have been found in AD, reflecting increased brain cholesterol turnover or cellular degradation, due to the neurodegenerative process. A case–control study was performed on 125 AD and 102 age- and gender-matched control subjects (CNT) from Hungary, to test the association of CYP46 T/C and apolipoprotein E (ApoE) gene polymorphisms in AD. The frequency of the CYP46 C allele was similar (χ²=0.647, df=1, P=0.421, exact P=0.466, OR=0.845; 95% CI: 0.561–1.274) in both groups (CNT: 27%; 95% CI: 21.3–33.4; AD 30%; 95% CI: 25.0–36.3). The ApoE ɛ4 allele was significantly over-represented (χ²=11.029, df=2, P=0.004) in the AD population (23.2%; 95% CI: 18.2–29.0) when compared with the CNT (11.3%; 95% CI: 7.4–16.6). The presence or absence of one or two CYP46C alleles together with the ApoE ɛ4 allele did not increase the risk of AD (OR=3.492; 95% CI: 1.401–8.707; P<0.007 and OR=3.714; 95% CI: 1.549–8.908; P<0.003, respectively). Our results indicate that the intron 2 T/C polymorphism of CYP46 gene (neither alone, nor together with the ɛ4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.     

The antimotility action of a trifluoromethyl ketone on some gram-negative bacteria

The inhibition of bacterial motility was studied by a trifluoro methyl ketone derivative on two Escherichia coli strains (wild strain having a proton pump system and the proton pump-deficient mutant strain) and two Helicobacter pylori strains (clarithromycin susceptible and clarithromycin resistant). Evidence is presented of the inhibitory action of 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18) on the proton motive forces of the two bacterial strains by affecting the action of biological motor and proton efflux in the membranes. The swimming, the forward motion was more sensitive than the vibration or tumbling to the inhibition. We suppose that the inhibiton of bacterial motility is related to the virulence of bacteria: consequently the pathogenicity can be reduced in the presence of TF18.     

Improved extraction procedure for the isolation of β-D-galactosidase from Escherichia coli

Summary A fast 4-step isolation procedure for -D-galactosidase from E. coli has been developed: cell disruption, two-stage aqueous two-phase extraction and ultrafiltration. A 60-fold purification of the enzyme with a total yield of 75% was achieved.     

Structure, enzymatic stability and antitumor activity of sea lamprey GnRH-III and its dimer derivatives

Direct antitumor activity of sea lamprey (Petromyzon marinus) gonadotropin-releasing hormone III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH(2); lGnRH-III) was described on several tumor cells. To improve the selectivity of antitumor effects without increasing the hormone releasing activity and to enhance the enzymatic stability, lGnRH-III dimers were prepared via disulfide bond formation. Our results demonstrate that the lGnRH-III dimer derivatives exhibited higher antiproliferative effect and enzymatic stability in comparison with the native lGnRH-III, while lower LH-releasing potency was determined. In order to find a correlation between the biological and structural features of these compounds, the conformation of lGnRH-III and its dimer derivatives was determined by ECD, VCD, FT-IR and (1)H NMR.     

Holocene mammal extinctions in the Carpathian Basin: a review

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Do short-lived and long-lived alien plant species differ regarding the traits associated with their success in the introduced range?

In spite of the several studies trying to identify the biological traits that are generally associated with the success of alien plant species, only a few traits are consistently shown to be important. Dividing the species into meaningful sub-categories may improve our ability to distinguish successful alien species. We asked whether there are differences between short-lived and long-lived herbaceous aliens regarding the biological traits associated with their success in their introduced range. We used the source-area approach to answer the question by performing a comparative study with those Central-European herbaceous plant species which are invasive or non-invasive aliens in the United States. Biological traits used in the analysis were extracted from European databases. The significant traits (with one exception) conferred invasiveness for only one of the two life history groups. These results outline a particular combination of competition and colonization in both groups, although achieved in different ways. Short-lived invasive species, which are supposed to be good colonizers with effective reproduction and dispersal, are backed by some kind of competitive ability conferred by height; while in the case of competitive and persistent long-lived species, the successful aliens are equipped with traits that make them better colonizers than other perennial alien species (e.g., tolerance for a wide range of anthropogenic disturbance, dispersal through water).     

Pharmacology of a new tritiated endomorphin-2 analog containing the proline mimetic cis-2-aminocyclohexanecarboxylic acid

As part of ongoing work aimed at generating proteolytically stable, readily applicable, radiolabeled endomorphin-2 (EM-2) analogs for elucidation of the topological requirements of peptide binding to μ-opioid receptors, we report here on the synthesis, radiolabeling, binding kinetics and binding site distribution of an EM-2 analog in which Pro² is replaced by 2-aminocyclohexanecarboxylic acid, ACHC. [³H][(1S,2R)ACHC]²EM-2 (specific activity 63.49 Ci × mmol⁻¹) bound specifically to its binding sites with high affinity (K_D = 0.55 ± 0.06 nM) and saturably, yielding a receptor density, B_max of 151 ± 4 fmol × mg protein⁻¹ in rat brain membranes. A similar affinity value was obtained in kinetic assays. Both Na⁺ and Gpp(NH)p decreased the affinity, proving the agonist character of the radioligand. Specific μ-opioid ligands displaced the radioligand with much higher affinities than did δ- and κ-ligands. The autoradiographic distribution of the binding sites of [³H][(1S,2R)ACHC]²EM-2 agreed well with the known locations of the μ-opioid receptors in the rat brain. In consequence of its high affinity, selectivity and enzymatic resistance [19], the new radioligand will be a good tool in studies of the topographical requirements of μ-opioid-specific peptide binding.