Erratum to: Attractor Dynamics and Thermodynamic Analogies in the Cerebral Cortex: Synchronous Oscillation,the Background EEG,and the Regulation of Attention

Ongoing changes in attention and cognition depend upon cortical/subcortical interactions, which select sequences of different spatial patterns of activation in the cortex.     

Environmental Fluctuations and Level of Density-Compensation Strongly Affects the Probability of Fixation and Fixation Times

The probability of, and time to, fixation of a mutation in a population has traditionally been studied by the classic Wright–Fisher model where population size is constant. Recent theoretical expansions have covered fluctuating populations in various ways but have not incorporated models of how the environment fluctuates in combination with different levels of density-compensation affecting fecundity. We tested the hypothesis that the probability of, and time to, fixation of neutral, advantageous and deleterious mutations is dependent on how the environment fluctuates over time, and on the level of density-compensation. We found that fixation probabilities and times were dependent on the pattern of autocorrelation of carrying capacity over time and interacted with density-compensation. The pattern found was most pronounced at small population sizes. The patterns differed greatly depending on whether the mutation was neutral, advantageous, or disadvantageous. The results indicate that the degree of mismatch between carrying capacity and population size is a key factor, rather than population size per se, and that effective population sizes can be very low also when the census population size is far above the carrying capacity. This study highlights the need for explicit population dynamic models and models for environmental fluctuations for the understanding of the dynamics of genes in populations.     

Mucolipidosis type IV and the mucolipins

MLIV (mucolipidosis type?IV) is a neurodegenerative lysosomal storage disorder caused by mutations in MCOLN1, a gene that encodes TRPML1 (mucolipin-1), a member of the TRPML (transient receptor potential mucolipin) cation channels. Two additional homologues are TRPML2 and TRPML3 comprising the TRPML subgroup in the TRP superfamily. The three proteins play apparently key roles along the endocytosis process, and thus their cellular localization varies among the different group members. Thus TRPML1 is localized exclusively to late endosomes and lysosomes, TRPML2 is primarily located in the recycling clathrin-independent GPI (glycosylphosphatidylinositol)-anchored proteins and early endosomes, and TRPML3 is primarily located in early endosomes. Apparently, all three proteins' main physiological function underlies Ca(2+) channelling, regulating the endocytosis process. Recent findings also indicate that the three TRPML proteins form heteromeric complexes at least in some of their cellular content. The physiological role of these complexes in lysosomal function remains to be elucidated, as well as their effect on the pathophysiology of MLIV. Another open question is whether any one of the TRPMLs bears additional function in channel activity.     

Association mapping, patterns of linkage disequilibrium and selection in the vicinity of the PHYTOCHROME C gene in pearl millet

Key message

Linkage analysis confirmed the association in the region of PHYC in pearl millet. The comparison of genes found in this region suggests that PHYC is the best candidate.

Abstract

Major efforts are currently underway to dissect the phenotype–genotype relationship in plants and animals using existing populations. This method exploits historical recombinations accumulated in these populations. However, linkage disequilibrium sometimes extends over a relatively long distance, particularly in genomic regions containing polymorphisms that have been targets for selection. In this case, many genes in the region could be statistically associated with the trait shaped by the selected polymorphism. Statistical analyses could help in identifying the best candidate genes into such a region where an association is found. In a previous study, we proposed that a fragment of the PHYTOCHROME C gene (PHYC) is associated with flowering time and morphological variations in pearl millet. In the present study, we first performed linkage analyses using three pearl millet F₂ families to confirm the presence of a QTL in the vicinity of PHYC. We then analyzed a wider genomic region of ~100 kb around PHYC to pinpoint the gene that best explains the association with the trait in this region. A panel of 90 pearl millet inbred lines was used to assess the association. We used a Markov chain Monte Carlo approach to compare 75 markers distributed along this 100-kb region. We found the best candidate markers on the PHYC gene. Signatures of selection in this region were assessed in an independent data set and pointed to the same gene. These results foster confidence in the likely role of PHYC in phenotypic variation and encourage the development of functional studies.     

Functional inference of the methylenetetrahydrofolate reductase 677 C > T and 1298A > C polymorphisms from a large-scale epidemiological study

Two functional single nucleotide polymorphisms, 677C > T and 1298A > C have been described for the methylenetetrahydrofolate (MTHFR) gene. Both are associated with reduced enzyme activity in vitro. For the 677T, but not the 1298C allele, significantly lower serum folate and higher plasma total homocysteine (tHcy) have been reported. We genotyped 10,034 middle-aged (50–64 years old) subjects and measured serum folate and tHcy. Within strata of 677 genotypes, 1,298 genotypes had significantly different serum folate and tHcy (P ≤ 0.03 for all comparisons). Each additional 1298C allele reduced mean serum folate and increased mean tHcy, by (on average) 4.5 and 3.0%, respectively. In comparison, within strata of 1,298 genotypes, the increase from no, to one 677T-allele reduced serum folate and increased tHcy by, 7.1 and 6.3%, respectively. Lowest serum folate and highest tHcy level was found for the 677TT/1298AA genotype. The difference in tHcy was significantly larger at low folate than at high folate when genotypes 677TT/1298AA and 677CT/1298AA, 677CT/1298AC and 677CC/1298AC, and genotypes 677CT/1298AC and 677CT/1298AA were compared. We interpreted these data in the context of a model of the MTHFR enzyme that describes the enzyme as a dimer that mainly exist in six different configurations. The model reconciled the observed phenotypic effects of the 677/1,298 combination genotypes with previous in vitro measurements, and identified enzyme configurations that are sensitive to low folate levels. In conclusion, this report demonstrates functional inference of the MTHFR 677 C > T and 1,298 A > C polymorphisms from a large-scale epidemiological study.     

Prey Selection,Vertical Migrations and the Impacts of Harvesting Upon the Population Dynamics of a Predator-Prey System

A model is developed to describe the interaction between a predator and two prey types located in different regions. Conditions for stability and persistence are analysed. The effects of harvesting the predators are investigated by making the predator mortality rate habitat dependent. Results demonstrate that for any given set of parameter values there is a value of the intrinsic preference of the predator for each prey type at which the system undergoes a Hopf bifurcation. Above this critical value the system evolves towards a stable equilibrium, whereas below it, stable limit cycles arise by Hopf bifurcations. Simulations demonstrate that the presence of demographic stochasticity may destabilise oscillatory populations, thereby causing population extinctions. An application of the model to the foraging behaviour of North Sea cod is described. It is shown that if the preferred prey is more productive, it is likely that the equilibrium will be stable, whereas if the less preferred prey is more productive, populations are likely to display cycles and in the stochastic case become extinct. As cod fishing mortality is increased, the point of bifurcation and region of parameter space for which the system is unstable decreases. An increased understanding of how cod behave may enable fish stocks to be managed more successfully, for example by indicating where marine reserves should be placed.     

1H, 13C, and 15N backbone and side-chain chemical shift assignments for the 29 kDa human galectin-1 protein dimer

Galectin-1 is an important regulator of leukocyte function and tumor angiogenesis. Recently, this lectin has been identified as a molecular target for the potent angiogenesis inhibitor anginex. Here, we report ¹H, ¹³C, and ¹⁵N chemical shift assignments for human galectin-1 as determined by using heteronuclear triple resonance NMR spectroscopy.     

1H, 13C, and 15N chemical shift assignments for the Eps15-EH2-stonin 2 complex

EH domains are protein–protein interaction domains that function in vesicular trafficking and endocytosis. Here, we report the NMR spectral assignments of the high-affinity complex between the second EH domain of Eps15 and a stonin 2 peptide—providing the basis for the characterization of a two-site binding mode.     

Backbone 1H, 15N, 13C and Ile, Leu, Val methyl chemical shift assignments for the 33.5 kDa N-terminal domain of Candida albicans ALS1

The agglutinin-like-sequence (ALS) family of adhesion proteins are a key virulence factor for C. albicans. These proteins have been implicated in several functions, notably adhesion and invasion of different cell types, as well as binding to peptides and proteins in the cell surface and extracellular matrix. In order to understand their binding mechanism and en route to a full structural determination by NMR, here we report the resonance assignments of backbone atoms plus Ile, Leu and Val methyls for residues 18–329 of ALS1, which comprises the 33.5 kDa binding domain.     

Differences in the C age, δC and δO of Holocene tufa and speleothem in the Dinaric Karst

We studied Holocene speleothems and tufa samples collected in numerous caves and rivers in the Dinaric Karst of Croatia, Slovenia, Bosnia and Herzegovina, as well as Serbia and Montenegro. Differences in the formation process of tufa and speleothems are discussed in the context of their isotopic composition (¹⁴C, ¹³C and ¹⁸O), as well as the chemistry of surface water (rivers, lakes) and drip water (in caves). The physical and chemical parameters monitored in the surface water (tufa precipitation) and drip water (speleothem precipitation) show that more stable conditions accompany speleothem rather than tufa formation. This is particularly obvious in the water temperature variations (2-22°C in surface water and 7-12°C in drip water) and in saturation index variation (3-11 in surface water and 1-6 in drip water). The range of ¹⁴C ages recorded by Holocene speleothems (∼12?000 yr) is wider by several thousands years than that of Holocene tufa samples (∼6000 yr). δ¹³C values for tufa samples range from −12‰ to −6‰ and for speleothem samples from −12‰ to +3‰ reflecting higher soil carbon and/or vegetation impact on the process of tufa than on speleothem formation. The differences in δ¹⁸O values of tufa and speleothem samples from different areas reflect different temperature conditions and differing isotopic composition in the water. The study shows that speleothems from the Dinaric Karst can be used as global palaeoclimatic records, whereas tufa records changes in the local palaeoenvironment.     

MARCH8 Ubiquitinates the Hepatitis C Virus Nonstructural 2 Protein and Mediates Viral Envelopment

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The Final Size of an Epidemic and Its Relation to the Basic Reproduction Number

We study the final size equation for an epidemic in a subdivided population with general mixing patterns among subgroups. The equation is determined by a matrix with the same spectrum as the next generation matrix and it exhibits a threshold controlled by the common dominant eigenvalue, the basic reproduction number R₀{\mathcal{R}_{0}}: There is a unique positive solution giving the size of the epidemic if and only if R₀{\mathcal{R}_{0}} exceeds unity. When mixing heterogeneities arise only from variation in contact rates and proportionate mixing, the final size of the epidemic in a heterogeneously mixing population is always smaller than that in a homogeneously mixing population with the same basic reproduction number R₀{\mathcal{R}_{0}}. For other mixing patterns, the relation may be reversed.     

Validated age and growth estimates for the shortfin mako, Isurus oxyrinchus, in the North Atlantic Ocean

Age and growth estimates for the shortfin mako, Isurus oxyrinchus, derived from vertebral centra of 258 specimens (118 males, 140 females), ranging in size from 64 to 340 cm fork length (FL) were compared with data from 22 tag–recaptured individuals (74–193 cm FL) and length–frequency data from 1822 individuals (1035 males, 787 females; 65–215 cm FL). Annual band-pair deposition, confirmed by a concurrent bomb radiocarbon validation study, was used as the basis for band interpretation. Validation was further confirmed with a tetracycline-injected male shortfin mako recaptured after being at liberty off South Africa for 1 year and aged at 18 years. Growth rates from tag–recapture analysis (GROTAG) were higher than those derived from vertebral annuli and were only available from sharks up to 193 cm FL at recapture. Modal length–frequency data were used to verify the first four age classes. Growth curves were fit using both von Bertalanffy and Gompertz models. The 3-parameter version of the von Bertalanffy growth function produced the most biologically reasonable values for males, based on observed data (L _∞  = 253 cm FL, K = 0.125 year^?1 (estimated longevity = 21 year), and L ₀ = 72 cm). The 3-parameter version of the Gompertz growth function produced the most biologically reasonable estimates, for females (L _∞  = 366 cm FL, K = 0.087 year^?1 (estimated longevity = 38 year) and L ₀ = 88 cm. Males and females were aged to 29 (260 cm FL) and 32 years (335 cm FL), respectively. Both sexes grew similarly to age 11 (207 cm FL, 212 cm FL for males and females, respectively) when the curve leveled in males and continued to rise in females. Age at 50% maturity was estimated at 8 years for males (185 cm FL) and 18 years for females (275 cm FL). The species grows slower, matures later and has a longer life span than previously reported in North Atlantic waters.     

1H, 13C, and 15N resonance assignments of reduced GrxS14 from Populus tremula × tremuloides

GrxS14 is a monothiol Glutaredoxin (Grx) from Populus tremula × tremuloides, which has a CGFS active site. GrxS14 is located in the chloroplasts and has been found to occur ether as an apo form or as a holo form with a [2Fe-2S] cluster. The holo form contains two monomers of apo GrxS14 bridged by the iron sulphur center, in the presence of two external glutathione molecules (Bandyopadhyay et al. 2008). The NMR assignments of the GrxS14 are essential for its solution structure determination.