MAINTENANCE OF GENETIC VARIATION IN IMMUNE DEFENSE OF A FRESHWATER SNAIL: ROLE OF ENVIRONMENTAL HETEROGENEITY

Natural populations often show genetic variation in pathogen resistance, which is paradoxal because natural selection is expected to erode genetic variation in fitness‐related traits. Several different factors have been suggested to maintain such variation, but their relative importance is still poorly understood. Here we examined if environmental heterogeneity and genetic trade‐offs could contribute to the maintenance of genetic variation in immune function of a freshwater snail Lymnaea stagnalis. We assessed the immunocompetence of snails originating from different families and maintained in different feeding treatments (ad libitum feeding, no food) by measuring the density of circulating hemocytes, phenoloxidase activity, and antibacterial activity of snail hemolymph. Food limitation reduced snail immune function, and we found significant among‐family variation in hemocyte concentration and PO activity, but not in antibacterial activity. Interestingly, food availability modified the family‐level variation observed in PO activity so that the relative immunocompetence of different snail families changed over environmental conditions (G × E interaction). We found no evidence for genetic trade‐offs between snail growth and immune defense nor among immune traits. Thus, our findings support the idea that environmental heterogeneity may promote maintenance of genetic variation in immune defense, but also suggest that different immune traits might not respond similarly to environmental variation.     

Oral health and morbidity--implications of oral infections on the elderly

Detrimental effects of oral infections on general health have been known for almost 3000 years. Modern studies, however, have cast new light on the pathogenic mechanisms by which oral infections appear to link with morbidity and mortality. In particular, among the elderly, poor dental health seems to associate with all-cause mortality. This review aims to provide an overview of present knowledge of these issues, starting from dental bacteraemia, oral mucosal infections and problems of drug resistance and, briefly, discussing what is known about the link between oral health and some systemic diseases such as atherosclerosis and type-2 diabetes. The main conclusions are that scientific evidence is still weak on these interactions and that the elderly should be better taken into account when planning future studies. Functions of the body differ in the frail and diseased from those of the young. Consequently, novel prevention and treatment strategies should be developed and properly tested for combating oral infections in elderly populations. Specific suggestions for further research are outlined.     

Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults

The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females.     

Bayesian search of functionally divergent protein subgroups and their function specific residues

MOTIVATION: The rapid increase in the amount of protein sequence data has created a need for an automated identification of evolutionarily related subgroups from large datasets. The existing methods typically require a priori specification of the number of putative groups, which defines the resolution of the classification solution. RESULTS: We introduce a Bayesian model-based approach to simultaneous identification of evolutionary groups and conserved parts of the protein sequences. The model-based approach provides an intuitive and efficient way of determining the number of groups from the sequence data, in contrast to the ad hoc methods often exploited for similar purposes. Our model recognizes the areas in the sequences that are relevant for the clustering and regards other areas as noise. We have implemented the method using a fast stochastic optimization algorithm which yields a clustering associated with the estimated maximum posterior probability. The method has been shown to have high specificity and sensitivity in simulated and real clustering tasks. With real datasets the method also highlights the residues close to the active site. AVAILABILITY: Software 'kPax' is available at http://www.rni.helsinki.fi/jic/softa.html     

Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes

Mechanical forces can stimulate the production of extracellular matrix molecules. We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine primary chondrocytes. The ultrasound-induced temperature rise was measured and its contribution to the synthesis was investigated using bare heat stimulus. Chondrocytes from five cellular isolations were exposed in triplicate to ultrasound (1 MHz, duty cycle 20%, pulse repetition frequency 1 kHz) at average intensity of 580 mW/cm2 for 10 minutes daily for 1-5 days. Temperature evolution was recorded during the sonication and corresponding temperature history was created using a controllable water bath. This exposure profile was used in 10-minute-long heat treatments of chondrocytes. Heat shock protein 70 (Hsp70) levels after one-time treatment to ultrasound and heat was analyzed by Western blotting, and proteoglycan synthesis was evaluated by 35S-sulfate incorporation. Ultrasound treatment did not induce Hsp70, while heat treatment caused a slight heat stress response. Proteoglycan synthesis was increased approximately 2-fold after 3-4 daily ultrasound stimulations, and remained at that level until day 5 in responsive cell isolates. However, chondrocytes from one donor cell isolation out of five remained non-responsive. Heat treatment alone did not increase proteoglycan synthesis. In conclusion, our study confirms that pulsed ultrasound stimulation can induce proteoglycan synthesis in chondrocytes.     

Spatial and temporal changes in occupancy frequency distribution patterns of freshwater macrophytes in Finland

A useful method for characterizing biological numerous assemblages at regional scales is the species occupancy frequency distribution (SOFD). An SOFD shows the number or proportion of study sites each species occurred. Species that occur at only a few sites are termed satellite species, while species that occur at many sites are termed core species.This study is the first to document and assess SOFD patterns in aquatic macrophytes. It characterizes SOFD patterns of freshwater macrophyte assemblages in Finland at two spatial and two temporal scales. For this, I analyzed three published datasets on freshwater macrophyte distributions: two from studies conducted at a local scale and the third from large national surveys. One local study and the national study also included data on temporal variation in species occupancy frequencies.In the national study, the number of core and satellite species varied slightly between the older and the newer survey, respectively. Among the 113 waterbodies surveyed as part of the national study, the SOFD followed a unimodal satellite pattern. However, for the older dataset (from the 1930s), a bimodal symmetric pattern also fit the SOFD data well. At the local scale, I observed geographical variation in SOFD patterns. The dataset from southern Finland followed a unimodal satellite SOFD pattern; data from central Finland instead displayed a bimodal symmetric SOFD pattern, although they also fit equally well with a bimodal truncated pattern. Moreover, temporal patterns in central Finland seemed to demonstrate a shift from a bimodal symmetric to a bimodal asymmetric SOFD probably.Geographical variation in the SOFD pattern may be due to variation in the regional species pool. The temporal changes in SOFD pattern may be due to lake eutrophication and anthropogenic disturbance around waterbodies, which may increase number of macrophyte species.     

Dental topography indicates ecological contraction of lemur communities

Understanding the paleoecology of extinct subfossil lemurs requires reconstruction of dietary preferences. Tooth morphology is strongly correlated with diet in living primates and is appropriate for inferring dietary ecology. Recently, dental topographic analysis has shown great promise in reconstructing diet from molar tooth form. Compared with traditionally used shearing metrics, dental topography is better suited for the extraordinary diversity of tooth form among subfossil lemurs and has been shown to be less sensitive to phylogenetic sources of shape variation. Specifically, we computed orientation patch counts rotated (OPCR) and Dirichlet normal energy (DNE) of molar teeth belonging to 14 species of subfossil lemurs and compared these values to those of an extant lemur sample. The two metrics succeeded in separating species in a manner that provides insights into both food processing and diet. We used them to examine the changes in lemur community ecology in Southern and Southwestern Madagascar that accompanied the extinction of giant lemurs. We show that the poverty of Madagascar's frugivore community is a long-standing phenomenon and that extinction of large-bodied lemurs in the South and Southwest resulted not merely in a loss of guild elements but also, most likely, in changes in the ecology of extant lemurs.     

Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome

Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delayed osseous maturation, expressive-language deficits, and a distinctive facial appearance. Occurrence is generally sporadic, although parent-to-child transmission has been reported on occasion. Employing whole-exome sequencing, we identified heterozygous truncating mutations in SRCAP in five unrelated individuals with sporadic FHS. Sanger sequencing identified mutations in SRCAP in eight more affected persons. Mutations were de novo in all six instances in which parental DNA was available. SRCAP is an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREB-binding protein (CREBBP, better known as CBP, the major cause of Rubinstein-Taybi syndrome [RTS]). Five SRCAP mutations, two of which are recurrent, were identified; all are tightly clustered within a small (111 codon) region of the final exon. These mutations are predicted to abolish three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact. Our findings show that SRCAP mutations are the major cause of FHS and offer an explanation for the clinical overlap between FHS and RTS.