First documentation of leopard seal predation of South Georgia pintail duck

Leopard seals are regular winter visitors to Bird Island, South Georgia, where they mostly prey on fur seals and penguins, and to a lesser extent on Antarctic krill and fish. Leopard seals can exploit many different species, but there are no records of predation on flying shorebirds in the wild. On 4 October 2008, an individually identified juvenile leopard seal female was observed killing and eating a South Georgia Pintail duck. It also preyed on Antarctic fur seals and gentoo and macaroni penguins during its 2-month temporary residency around the island. The varied diet of this seal exemplifies the generalist prey utilization typical of its species. Long-term diet studies at Bird Island and the published record suggest that predation on ducks is a rather exceptional finding; individual ducks are more likely to escape leopard seal attacks than penguins and provide a far less substantial ration. This note documents the first observation of this species of duck in the diet of leopard seals.     

Investigation of Bolivian plant extracts for their radical scavenging activity and antioxidant activity

Fifty-four different extracts of nine Bolivian plants belonging to the family Asteraceae were evaluated for their radical scavenging activity by the DPPH*, NBT/hypoxanthine superoxide, and (*)OH/luminol chemiluminescence methods, and for their antioxidant activity by the beta-carotene bleaching test. The total phenolic content was also determined by the Folin-Ciocalteu method, and the oxidative stability by the Rancimat test. Both remarkably high phenolic content and radical scavenging and antioxidant activities were found mainly in the ethyl acetate fractions among the different plant extracts. Some ethyl acetate and even some defatted crude extracts exhibited activities comparable to those of commercial extracts/compounds, thus making it possible to consider some of the studied plants as a potential source of antioxidants of natural origin.     

Retinaldehyde is a substrate for human aldo-keto reductases of the 1C subfamily

Human AKR (aldo-keto reductase) 1C proteins (AKR1C1-AKR1C4) exhibit relevant activity with steroids, regulating hormone signalling at the pre-receptor level. In the present study, investigate the activity of the four human AKR1C enzymes with retinol and retinaldehyde. All of the enzymes except AKR1C2 showed retinaldehyde reductase activity with low Km values (~1 μM). The kcat values were also low (0.18-0.6 min-1), except for AKR1C3 reduction of 9-cis-retinaldehyde whose kcat was remarkably higher (13 min-1). Structural modelling of the AKR1C complexes with 9-cis-retinaldehyde indicated a distinct conformation of Trp227, caused by changes in residue 226 that may contribute to the activity differences observed. This was partially supported by the kinetics of the AKR1C3 R226P mutant. Retinol/retinaldehyde conversion, combined with the use of the inhibitor flufenamic acid, indicated a relevant role for endogenous AKR1Cs in retinaldehyde reduction in MCF-7 breast cancer cells. Overexpression of AKR1C proteins depleted RA (retinoic acid) transactivation in HeLa cells treated with retinol. Thus AKR1Cs may decrease RA levels in vivo. Finally, by using lithocholic acid as an AKR1C3 inhibitor and UVI2024 as an RA receptor antagonist, we provide evidence that the pro-proliferative action of AKR1C3 in HL-60 cells involves the RA signalling pathway and that this is in part due to the retinaldehyde reductase activity of AKR1C3.     

METABOLIC FLUX IS A DETERMINANT OF THE EVOLUTIONARY RATES OF ENZYME‐ENCODING GENES

Relationships between evolutionary rates and gene properties on a genomic, functional, pathway, or system level are being explored to unravel the principles of the evolutionary process. In particular, functional network properties have been analyzed to recognize the constraints they may impose on the evolutionary fate of genes. Here we took as a case study the core metabolic network in human erythrocytes and we analyzed the relationship between the evolutionary rates of its genes and the metabolic flux distribution throughout it. We found that metabolic flux correlates with the ratio of nonsynonymous to synonymous substitution rates. Genes encoding enzymes that carry high fluxes have been more constrained in their evolution, while purifying selection is more relaxed in genes encoding enzymes carrying low metabolic fluxes. These results demonstrate the importance of considering the dynamical functioning of gene networks when assessing the action of selection on system‐level properties.     

PKLR- GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations

Haplotype diversity in a genomic region of approximately 70 kb in 1q21 between genes PKLR and GBA was characterized by typing one single nucleotide polymorphism (SNP) in PKLR, two SNPs in GBA and one short tandem repeat polymorphism (STRP) in PKLR in 1792 chromosomes from 17 worldwide populations. Two other SNPs in GBA were typed in three African populations. Most chromosomes carried one of either two phylogenetically distinct haplotypes with different alleles at each site. Allele diversity at the STRP was tightly linked to haplotype background. Linkage disequilibrium (LD) was highly significant for all SNP pairs in all populations, although it was, on average, slightly higher in non-African populations than in sub-Saharan Africans. Variation at PKLR-GBA was also tightly linked to that at the GBA pseudogene, 16 kb downstream from GBA. Thus, a 90 kb-long LD block was observed, which points to a low recombination rate in this region. Detailed haplotype phylogeny suggests that the chimpanzee GBA haplotype is not one of the two most frequent haplotypes. Based on variability at the PKLR STRP and on the geographical distribution of LD, the expansion of the two main haplotypes may have predated the "Out of Africa" expansion of anatomically modern humans. LD and STRP variability in non-Africans are approximately 87% of those in Africans, in contrast with other loci; this implies that the "out of Africa" bottleneck may have had a broad distribution of effects across loci.     

Complete reversal of coenzyme specificity by concerted mutation of three consecutive residues in alcohol dehydrogenase

Gastric tissues from amphibian Rana perezi express the only vertebrate alcohol dehydrogenase (ADH8) that is specific for NADP(H) instead of NAD(H). In the crystallographic ADH8-NADP+ complex, a binding pocket for the extra phosphate group of coenzyme is formed by ADH8-specific residues Gly223-Thr224-His225, and the highly conserved Leu200 and Lys228. To investigate the minimal structural determinants for coenzyme specificity, several ADH8 mutants involving residues 223 to 225 were engineered and kinetically characterized. Computer-assisted modeling of the docked coenzymes was also performed with the mutant enzymes and compared with the wild-type crystallographic binary complex. The G223D mutant, having a negative charge in the phosphate-binding site, still preferred NADP(H) over NAD(H), as did the T224I and H225N mutants. Catalytic efficiency with NADP(H) dropped dramatically in the double mutants, G223D/T224I and T224I/H225N, and in the triple mutant, G223D/T224I/H225N (kcat/KmNADPH = 760 mm-1 min-1), as compared with the wild-type enzyme (kcat/KmNADPH = 133330 mm-1 min-1). This was associated with a lower binding affinity for NADP+ and a change in the rate-limiting step. Conversely, in the triple mutant, catalytic efficiency with NAD(H) increased, reaching values (kcat/KmNADH = 155000 mm-1 min-1) similar to those of the wild-type enzyme with NADP(H). The complete reversal of ADH8 coenzyme specificity was therefore attained by the substitution of only three consecutive residues in the phosphate-binding site, an unprecedented achievement within the ADH family.     

Erratum to “Random models of Menzerath–Altmann law in genomes” (BioSystems 107(3) (2012) 167–173)

Here we improve the mathematical arguments of Baixeries et al (BioSystems 107(3) (2012) 167–173). The corrections do not alter the conclusion that the random breakage model yields an insufficient fit to the scaling of mean chromosome length as a function of chromosome number in real genomes.     

C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients

A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.     

A genome-wide survey does not show the genetic distinctiveness of Basques

Basques are a cultural isolate, and, according to mainly allele frequencies of classical polymorphisms, also a genetic isolate. We investigated the differentiation of Spanish Basques from the rest of Iberian populations by means of a dense, genome-wide SNP array. We found that F _ST distances between Spanish Basques and other populations were similar to those between pairs of non-Basque populations. The same result is found in a PCA of individuals, showing a general distinction between Iberians and other South Europeans independently of being Basques. Pathogen-mediated natural selection may be responsible for the high differentiation previously reported for Basques at very specific genes such as ABO, RH, and HLA. Thus, Basques cannot be considered a genetic outlier under a general genome scope and interpretations on their origin may have to be revised.