Balance between Noise and Information Flow Maximizes Set Complexity of Network Dynamics

Boolean networks have been used as a discrete model for several biological systems, including metabolic and genetic regulatory networks. Due to their simplicity they offer a firm foundation for generic studies of physical systems. In this work we show, using a measure of context-dependent information, set complexity, that prior to reaching an attractor, random Boolean networks pass through a transient state characterized by high complexity. We justify this finding with a use of another measure of complexity, namely, the statistical complexity. We show that the networks can be tuned to the regime of maximal complexity by adding a suitable amount of noise to the deterministic Boolean dynamics. In fact, we show that for networks with Poisson degree distributions, all networks ranging from subcritical to slightly supercritical can be tuned with noise to reach maximal set complexity in their dynamics. For networks with a fixed number of inputs this is true for near-to-critical networks. This increase in complexity is obtained at the expense of disruption in information flow. For a large ensemble of networks showing maximal complexity, there exists a balance between noise and contracting dynamics in the state space. In networks that are close to critical the intrinsic noise required for the tuning is smaller and thus also has the smallest effect in terms of the information processing in the system. Our results suggest that the maximization of complexity near to the state transition might be a more general phenomenon in physical systems, and that noise present in a system may in fact be useful in retaining the system in a state with high information content.     

The Effect of the pH of Meat on the Boiling Test

The effect of the pH on the boiling test was studied in 68 beef and 108 pork muscles. The pH had a significant effect on the sensory scores obtained from the boiling test. The effect was particularly pronounced in the odour of meat. In beef the odour scores remain steady for samples with a pH value under about 6.2 and start to increase rapidly in higher pH values. In pork the increase in scores appears to be linear. The odour observed in high pH meat was described by the judges as abnormal and ammonialike. In the case of meat with a high pH, the results of the boiling test at meat inspection should be interpreted with extreme caution.     

Migration strategies of the Baltic dunlin: rapid jump migration in the autumn but slower skipping type spring migration

Migration during spring is usually faster than during autumn because of competition for breeding territories. In some cases, however, the costs and benefits associated with the environment can lead to slower spring migration, but examples are quite rare. We compared seasonal migration strategies of the endangered Baltic population of the dunlin Calidris alpina schinzii using light‐level geolocator data from 26 individuals breeding in Finland. Autumn migration was faster, with individuals showing a ‘jump’ and ‘skipping’ migration strategy characterised by fewer stationary periods, shorter total stopping time and faster flight. Spring migration was slower, with individuals using a ‘skipping’ strategy. The duration of migration was longer for early departing birds during spring but not during autumn suggesting that early spring migrants are prevented from arriving to the breeding areas or that fueling conditions are worse on the stopover sites for early arriving individuals. Dunlins showed high migratory connectivity. All individuals had one long staging at the Wadden Sea in the autumn after which half of the individuals flew 4500 km non‐stop to Banc d’Arguin, Mauritania. The other half stopped briefly on the Atlantic coast on their way to Mauritania. One bird wintered on the coast of Portugal. Nine individuals that carried geolocators for two years were site faithful to their final non‐breeding sites. Based on the strategies during the non‐breeding period we identified, Baltic dunlin may be especially vulnerable to rapid environmental changes at the staging and non‐breeding areas. Consequently, the preservation of the identified non‐breeding areas is important for their conservation.     

Can re-establishment of cattle grazing restore bryophyte diversity in abandoned mesic semi-natural grasslands?

Changes of agricultural practices have led to decline of semi-natural habitats sustained by traditional animal husbandry in many European regions. The abandonment of semi-natural pastures leads to increase of vascular plant biomass and subsequent decline of weak competitors such as bryophytes. Re-establishing traditional animal husbandry may potentially restore biodiversity but the success of such measures remains insufficiently known. In this study, we asked if re-establishing cattle grazing on previously abandoned grasslands will restore their bryophyte communities. The effect of cattle grazing on bryophyte communities of mesic semi-natural grasslands was studied in south-western Finland in a comparison of (i) continuously grazed pastures, (ii) previously abandoned pastures where grazing was re-established during 1990s, and (iii) abandoned pastures, where grazing had ceased during late 1960s to early 1980s. The average cover, species richness, species density and species diversity of bryophytes were significantly higher in the continuously grazed than in the abandoned grasslands. Ordination analyses revealed clear differences also in community structure between the management classes. Re-established grasslands were ecologically heterogeneous and situated in between the continuously grazed and abandoned grasslands in all characteristics, indicating variable effect of the restoration measure. Seventeen bryophyte species were recognized as significant indicators of the three grassland classes, four of which could be used as indicators of valuable grassland habitats. Although there was variation in the consequences of re-introduction of grazing, the results give evidence of positive effect of grazing on regaining bryophyte diversity of abandoned grasslands.     

Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis

D-bifunctional protein (DBP) deficiency is an autosomal recessive inborn error of peroxisomal fatty acid oxidation. The clinical presentation of DBP deficiency is usually very severe, but a few patients with a relatively mild presentation have been identified. In this article, we report the mutational spectrum of DBP deficiency on the basis of molecular analysis in 110 patients. We identified 61 different mutations by DBP cDNA analysis, 48 of which have not been reported previously. The predicted effects of the different disease-causing amino acid changes on protein structure were determined using the crystal structures of the (3R)-hydroxyacyl-coenzyme A (CoA) dehydrogenase unit of rat DBP and the 2-enoyl-CoA hydratase 2 unit and liganded sterol carrier protein 2-like unit of human DBP. The effects ranged from the replacement of catalytic amino acid residues or residues in direct contact with the substrate or cofactor to disturbances of protein folding or dimerization of the subunits. To study whether there is a genotype-phenotype correlation for DBP deficiency, these structure-based analyses were combined with extensive biochemical analyses of patient material (cultured skin fibroblasts and plasma) and available clinical information on the patients. We found that the effect of the mutations identified in patients with a relatively mild clinical and biochemical presentation was less detrimental to the protein structure than the effect of mutations identified in those with a very severe presentation. These results suggest that the amount of residual DBP activity correlates with the severity of the phenotype. From our data, we conclude that, on the basis of the predicted effect of the mutations on protein structure, a genotype-phenotype correlation exists for DBP deficiency.     

Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases

N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N′-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N′-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N′-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [K _m(APAO) = 10 μM, k _cat(APAO) = 1.1 s⁻¹ and K _m(SMO) = 28 μM, k _cat(SMO) = 0.8 s⁻¹, respectively], metabolized BnEtSPM to EtSPD [K _m(APAO) = 0.9 μM, k _cat(APAO) = 1.1 s⁻¹ and K _m(SMO) = 51 μM, k _cat(SMO) = 0.4 s⁻¹, respectively], and metabolized DBSPM to BnSPD [K _m(APAO) = 5.4 μM, k _cat(APAO) = 2.0 s⁻¹ and K _m(SMO) = 33 μM, k _cat(SMO) = 0.3 s⁻¹, respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM K _m(APAO) = 16 μM, k _cat(APAO) = 1.5 s⁻¹; K _m(SMO) = 25 μM, k _cat(SMO) = 8.2 s⁻¹; BnSPM K _m(APAO) = 6.0 μM, k _cat(APAO) = 2.8 s⁻¹; K _m(SMO) = 19 μM, k _cat(SMO) = 0.8 s⁻¹, respectively]. Surprisingly, EtSPD [K _m(APAO) = 37 μM, k _cat(APAO) = 0.1 s⁻¹; K _m(SMO) = 48 μM, k _cat(SMO) = 0.05 s⁻¹] and BnSPD [K _m(APAO) = 2.5 μM, k _cat(APAO) = 3.5 s⁻¹; K _m(SMO) = 60 μM, k _cat(SMO) = 0.54 s⁻¹] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues.     

α-Methylspermidine protects against carbon tetrachloride-induced hepatic and pancreatic damage

The role of polyamines in carbon tetrachloride (CCl₄)-induced organ injury was studied in syngenic rats and transgenic rats with activated polyamine catabolism. In syngenic rats, administration of CCl₄ resulted in the induction of hepatic spermidine/spermine N ¹-acetyltransferase (SSAT), accumulation of putrescine, reduction in spermine level and appearance of moderate hepatic injury within 24 h. Upon treatment with CCl₄, transgenic rats overexpressing SSAT displayed induction of both hepatic and pancreatic SSAT, with subsequent accumulation of putrescine and decrease of both spermidine and spermine pools. Administration of CCl₄ in SSAT transgenic rats induced not only massive hepatic injury, but also severe acute necrotizing pancreatitis. Pretreatment of the animals with catabolically stable functional polyamine mimetic, α-methylspermidine (MeSpd) prevented pancreatic and hepatic injury in SSAT rats and markedly reduced liver damage in syngenic animals. As assessed by immunostaining of proliferating cell nuclear antigen, MeSpd increased the amount of regenerating hepatocytes in both genotypes. These results show that CCl₄ induces hepatic and pancreatic polyamine catabolism, and the extent of organ damage correlates with the degree of polyamine depletion. Furthermore, MeSpd protects against CCl₄-induced hepatic and pancreatic damage and promotes tissue regeneration.