Present genetic structure revealed by microsatellites reflects recent history of the Finnish moose (Alces alces)

Genetic structures of Holarctic species are largely formed by Pleistocene colonisation history, dispersal capacity and interactions between biotic and abiotic factors, even though the human impact can also be significant. The Holarctic moose (Alces alces) arrived in Fennoscandia around 9,000–8,000 years ago, and it has been exploited by humans ever since. During the last 400 years, the Finnish moose population has suffered from several population declines, and even local and regional extirpations have occurred. The purpose of the present study is to describe the genetic variation and population structure of the Finnish moose in order to clarify how historical events and human exploitation have influenced the present-day genetic patterns. Altogether 130 moose individuals from seven sampling sites in Finland were analysed at ten microsatellite loci. A variety of population genetic and coalescent-based methods was applied. The Finnish moose population was found to be divided into southern and northern subpopulations with additional lower hierarchical genetic structure. The estimated time of divergence between these two subpopulations was about 96–238 years ago. In addition, an isolation-by-distance pattern was discovered.     

Loss of Competition in the Outside Host Environment Generates Outbreaks of Environmental Opportunist Pathogens

Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka–Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens.     

Cole Disease Results from Mutations in ENPP1

The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases.     

Diseases of epidermal keratins and their linker proteins

Epidermal keratins, a diverse group of structural proteins, form intermediate filament networks responsible for the structural integrity of keratinocytes. The networks extend from the nucleus of the epidermal cells to the plasma membrane where the keratins attach to linker proteins which are part of desmosomal and hemidesmosomal attachment complexes. The expression of specific keratin genes is regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Progress in molecular characterization of the epidermal keratins and their linker proteins has formed the basis to identify mutations which are associated with distinct cutaneous manifestations in patients with genodermatoses. The precise phenotype of each disease apparently reflects the spatial level of expression of the mutated genes, as well as the types and positions of the mutations and their consequences at mRNA and protein levels. Identification of specific mutations in keratinization disorders has provided the basis for improved diagnosis and subclassification with prognostic implications and has formed the platform for prenatal testing and preimplantation genetic diagnosis. Finally, precise knowledge of the mutations is a prerequisite for development of gene therapy approaches to counteract, and potentially cure, these often devastating and currently intractable diseases.     

Population structure,life cycle,and trophic niche of the glacial relict amphipod,Gammaracanthus lacustris,in a large boreal lake

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Epizootic cutaneous papillomatosis, cortisol and male ornamentation during and after breeding in the roach Rutilus rutilus

The prevalence of epidermal papillomatosis in roach is known to peak during the spawning period and to be higher in males than in females. The high occurrence of papillomatosis in polluted waters suggests that stress may contribute to the outbreak of the disease. However, little is known about breeding-induced stress in fish and its relationship with diseases. In this study, plasma cortisol concentration, hematocrit and the relative size of the spleen were determined in healthy and diseased male and female roach Rutilus rutilus during and shortly after spawning in a wild population. In addition, the sexual ornamentation (breeding tubercles on the lateral sides and on the frontal) of male roach during spawning was examined. Plasma cortisol concentration was higher during than after the spawning period, and higher in males than in females during spawning, indicating a spawning-induced stress and higher spawning stress among males. There was no correlation between cortisol concentration and the intensity of papillomatosis (number of scales under papilloma tumors) among the diseased fish. However, the significant interaction sex x disease status revealed by ANCOVA suggested that diseased males could be more prone to increased cortisol levels than diseased females or healthy males. Hematocrit values (ratio of the volume of red blood cells to total volume of blood) but not condition factor were lowered in papilloma-diseased fish after spawning. The relative size of the spleen was greater in males than in females. The number of frontal breeding tubercles correlated negatively with the intensity of papillomatosis. Experimental studies are needed to investigate the association of papillomatosis with stress and cortisol.     

Expression and characterization of recombinant human UDP-glucuronosyltransferases (UGTs). UGT1A9 is more resistant to detergent inhibition than other UGTs and was purified as an active dimeric enzyme

Eight human liver UDP-glucuronosyltransferases (UGTs) were expressed in baculovirus-infected insect cells as fusion proteins carrying a short C-terminal extension that ends with 6 histidine residues (His tag). The activity of recombinant UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT2B4, UGT2B7, and UGT2B15 was almost fully inhibited by 0.2% Triton X-100. In the case of UGT1A9, however, glucuronidation of alpha-naphthol and scopoletin was resistant to such inhibition, whereas glucuronidation of entacapone and several other aglycones was sensitive. His-tagged UGT1A9 was purified by immobilized metal-chelating chromatography (IMAC). Purified UGT1A9 glucuronidated scopoletin at a high rate, whereas its glucuronidation activity toward entacapone was low and largely dependent on phospholipid addition. Recombinant UGT1A9 in which the His tag was replaced by hemagglutinin antigenic peptide (HA tag) was also prepared. Insect cells were co-infected with baculoviruses encoding both HA-tagged and His-tagged UGT1A9. Membranes from the co-infected cells, or a mixture of membranes from separately infected cells, were subjected to detergent extraction and IMAC, and the resulting fractions were analyzed for the presence of each type of UGT1A9 using tag-specific antibodies. In the case of separate infection, the HA-tagged UGT1A9 did not bind to the column. When co-infected with His-tagged UGT1A9, however, part of the HA-tagged enzyme was bound to the column and was eluted by imidazole concentration gradient together with the His-tagged UGT1A9, suggesting the formation of stable dimers that contain one His-tagged and one HA-tagged UGT1A9 monomers.     

Multilevel phenotypic selection on morphological characters in a metapopulation of Silene tatarica

This study partitions selection in a natural metapopulation of a riparian plant species, Silene tatarica, into individual- and patch-level components by using contextual analysis, in which a patch refers to a spatially distinct stand of individual plants. We estimated selection gradients for two morphological characters (plant height and number of stems), their respective patch means, and plant density with respect to reproductive success in a two-year study. The approach was also extended to partition selection separately within habitats with varying degrees of exposure to river disturbances and herbivory. The selection differentials and gradients for plant height were positive at both individual and patch levels, with selection forces highest in the closed habitat with low exposure to disturbance. This pattern suggests that local groups with taller than average plants are more visible to pollinators than to groups that are shorter than average plants; and, within patches, individuals with short stature are visited less often than taller ones. Selection on the number of stems was in opposition at individual and patch levels. At the individual level the character was selected toward higher values, whereas selection at the patch-level favored smaller mean number of stems. The strength of the latter component was associated with the intensity of herbivory in different habitats, suggesting that the patch-level selection against a large number of stems might be due to high attractiveness of such patches to the main herbivore, reindeer. Consequently, direction and strength of selection in spatially structured populations may depend significantly on fitness effects arising at the group level.     

GRACILE syndrome,a lethal metabolic disorder with iron overload,is caused by a point mutation in BCS1L

GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. We previously localized the causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we report the molecular defect causing this metabolic disorder, by identifying a homozygous missense mutation that results in an S78G amino acid change in the BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different mutations in three British infants. BCS1L, a mitochondrial inner-membrane protein, is a chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Pulse-chase experiments performed in COS-1 cells indicated that the S78G amino acid change results in instability of the polypeptide, and yeast complementation studies revealed a functional defect in the mutated BCS1L protein. Four different mutations in the BCS1L gene have been reported elsewhere, in Turkish patients with a distinctly different phenotype. Interestingly, the British and Turkish patients had complex III deficiency, whereas in the Finnish patients with GRACILE syndrome complex III activity was within the normal range, implying that BCS1L has another cellular function that is uncharacterized but essential and is putatively involved in iron metabolism.     

Cholesterol efflux from larval Manduca sexta fat body in vitro: high-density lipophorin as the acceptor

The objective of this study was to characterize the transfer of cholesterol from Manduca sexta larvae fat body to high-density lipophorin. [³H]-Cholesterol-labeled fat body was incubated with lipophorin under different conditions and cholesterol transfer was determined. Transfer rate exhibited a hyperbolic dependency on lipophorin concentration with an apparent K_m of 3.6 mg/ml, which is consistent with either an aqueous diffusion mechanism of cholesterol transfer or a receptor-mediated process. Several results, including the high K_m, the high activation energy, and the lack of Ca²⁺ dependence favor aqueous diffusion model. In addition, anti-lipid transfer particle antibodies had only a small inhibitory effect, suggesting it is not involved in cholesterol transfer. However, the transfer was inhibited in the presence of suramin, which would be consistent with a receptor-mediated process. The effects of suramin may be complex because it can change membrane properties when bound to the lipophorin receptor and affect the rate of cholesterol desorption. The preponderance of data suggests that the export of cholesterol from fat body to lipophorin follows a simple aqueous diffusion pathway. Although we cannot completely exclude some contribution from a receptor-mediated pathway, it seems that if such a pathway were present, it represents a minor route.