Lifestyle, genetics, and disease in Sami

Aim

To present a summary of the lifestyle, genetic origin, diet, and disease in the population of Sami, indigenous people of northern Fennoscandia.

Method

A survey of the available scientific literature and preliminary results from our own study of the Swedish Sami population.

Results

The Sami probably have a heterogeneous genetic origin, with a major contribution of continental or Eastern European tribes and a smaller contribution from Asia. The traditional Sami diet, high in animal products, persists in Sami groups still involved with reindeer herding, but others have adopted a diet typical of Western cultures. Early reports indicated a lower prevalence of heart disease and most cancers, except stomach cancer. Recent studies have not found a lower risk of heart disease, but have consistently shown an overall reduced cancer risk. Sami have been reported to share some specific health-related genetic polymorphisms with other European populations, but none that would explain the observed differences in disease risk.

Conclusion

The genetic structure of the Sami population makes it suitable for studies of the genetic and environmental factors influencing the development of common diseases. The difference in incidence of heart disease between studies may reflect the ongoing transition from a traditional to a more Westernized lifestyle. The ability to compare population segments with different lifestyles, combined with the genetic structure of the population, creates unusual possibilities for studies of the genetic and environmental factors involved in the development of common disease.Sami are the indigenous people of the northernmost parts of Sweden, Finland, Norway, and the Kola Peninsula of Russia. The Sami speak a language belonging to the Finno-Ugric branch of the Uralic language family with Finns, Karelians, and Estonians as their closest linguistic neighbors. The Sami languages can be further divided into 10 distinct extant languages. Sami are believed to have been present in the area from soon after glacial ice-sheet retreated. The Sami where initially hunters (mainly of reindeer and moose), but over time they domesticated the reindeer and became reindeer herders. Today, the Sami population is estimated to be less than 100 000 individuals (1). Some of the Sami are still reindeer herders and maintain a traditional lifestyle linked to the annual migration of the reindeer between summer and winter grazing areas, while the rest have other occupations. The Sami population is not known to have experienced any dramatic population changes and until recent, marriages between Sami and non-Sami families have been infrequent.     

Force-, power-, and elasticity-velocity relationships in walking,running, and jumping

Summary Ground reaction forces and mechanical power were investigated when the subjects walked normally, while they were racing or running at four speeds, and when they performed the running long jump take-off. In addition, the apparent spring constants of the support leg in eccentric and concentric phases were investigated at the four running speeds, during the running long jump take-off, and in the triple jump. Six club level track and field athletes, four national level long jumpers, and six national level triple jumpers took part in the study. Cinematographic technique and a mathematical model of hopping (Alexander and Vernon 1975) were employed in the analysis. Force and power values were found to vary in the following order (from highest to lowest): long jump take-off, maximal running speed, submaximal running (80, 60, and 40% of maximum speed), racing gait, and normal gait. The data disclosed that the measured parameters had the highest values in the long jump take-off performed by the long jump athletes. Their peak values were: resultant ground reaction force 3270±74 N and mechanical power 160.1±10.5 J×kg^–1×s^–1. For the track and field athletes the values were 2010±80 N and 126.0±12.6 J ×kg^–1×s^–1. The apparent spring constant values of the support leg in the national level jumper group were in eccentric phase 30.54±8.38 N×mm^–1 ×kg^–1 and in concentric phase 0.129±0.012 N×mm^–1×kg^–1. In the track and field athletes the values were 13.97±1.01 N×mm^–1×kg^–1 and 0.093±0.003 N×mm^–1×kg^–1, respectively. In general, the increase in force and mechanical power output was related to the value of the apparent spring constant of the support leg in the eccentric phase. The spring constant in the eccentric phase increased with the velocity of motion in running, the long jump take-off and the triple jump. This suggests that it may be possible to use this parameter as a measure of mechanical performance, as it may reflect the combined elasticity of muscles, tendons, and bones.     

Inflammation, endothelium, and coagulation in sepsis

Sepsis is a systemic response to infection, and symptoms are produced by host defense systems rather than by the invading pathogens. Amongst the most prominent features of sepsis, contributing significantly to its outcome, is activation of coagulation with concurrent down-regulation of anticoagulant systems and fibrinolysis. Inflammation-induced coagulation on its turn contributes to inflammation. Another important feature of sepsis, associated with key symptoms such as hypovolemia and hypotension, is endothelial dysfunction. Under normal conditions, the endothelium provides for an anticoagulant surface, a property that is lost in sepsis. In this review, data about the interplay between inflammation and coagulation in sepsis are summarized with a special focus on the influence of the endothelium on inflammation-induced coagulation and vice versa. Possible procoagulant properties of the endothelium are described, such as expression of tissue factor (TF) and von Willebrand factor and interaction with platelets. Possible procoagulant roles of microparticles, circulating endothelial cells and endothelial apoptosis, are also discussed. Moreover, the important roles of the endothelium in down-regulating the anticoagulants TF pathway inhibitor, antithrombin, and the protein C (PC) system and inhibition of fibrinolysis are discussed. The influence of coagulation on its turn on inflammation and the endothelium is described with a special focus on protease-activated receptors (PARs). We conclude that the relationship between endothelium and coagulation in sepsis is tight and that further research is needed, for example, to better understand the role of activated PC signaling via PAR-1, the role of the endothelial PC receptor herein, and the role of the glycocalyx.     

Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance

Effects of nicotine and caffeine, separately and in combination, were assessed in 12 male habitual smokers in a repeated-measures design. Caffeine (0-mg vs. two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs. 1.0-mg machine-delivered dose vs. 0.05-mg machine-delivered dose). Participants smoked a total of five cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on electroencephalogram (EEG) power; however, these effects were modulated by the eyes open versus closed condition, the other drug, and electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs.     

Diethylstilbestrol, genetics, teratogenesis, and tumor spectrum in humans

Diethylstilbestrol (DES) is the first example of transplacental carcinogenesis in humans, as evidenced by an excess of clear cell adenocarcinoma of the vagina and cervix in exposed women. We hypothesize that: 1) in utero DES exposure will be responsible for a broader spectrum of cancer with variable age of onset as a function of latency effects in exposed humans of both sexes; 2) teratogenicity of DES will be more far-reaching than currently recognized and will harbor cancer implications in the face of known associations between teratogenesis and carcinogenesis; and 3) genetic heterogeneity will be a critical etiologic discriminant in DES associated cancer. This hypothesis embraces a prodigious body of data at the infrahuman level, as well as extant pharmacogenetic and ecogenetic observations in humans which signify heritable variations in response to environmental carcinogenic exposures. This hypothesis has important implications for drug testing with appropriate preventive strategies. Herein, particular restraints with monitoring through governmental legal channels must be employed. Past experience has clearly indicated negligence in shouldering this responsibility by both the pharmaceutical industry and government regulatory bodies.     

Lifespan, QTLs, age-specificity, and pleiotropy in Drosophila.

We have constructed a set of 120 recombinant inbred lines for use in studies of the genetics of lifespan in Drosophila. The lines are derived from Luckinbill and Clare's (Heredity 55 (1985) 9) artificial selection experiment for increased lifespan. Inbred lines retain the relative lifespan characteristics of the experimental and control stocks from which they are derived. Mapping experiments suggest that a small number of QTLs accounts for much of the selection response. The age-specificity of genetic effects is best visualized in three-dimensional QTL maps of age-specific mortality. QTLs are shared by males and females, and have effects on age-specific mortality that are positively correlated across ages, with different times of onset. There is evidence for positively correlated pleiotropic effects of lifespan QTLs on mid-life fertility and resistance to an oxidizing chemical, and a striking lack of evidence for negative pleiotropy.     

Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro

Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene delivery to the central nervous system and are capable of transducing neurons and glia in vitro. In this study, seven serotypes of a rAAV vector expressing green fluorescent protein (GFP) were characterized for tropism and toxicity in primary cortical cells derived from embryonic rat brain. At 2 days after transduction, serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days post-transduction expression was neuronal except for AAV5. AAV2 and 9 produced minimal GFP expression. Using cell viability assays, toxicity was observed at higher multiplicities of infection (MOI) for all serotypes except AAV2 and 9. The toxicity of AAV1 and 5-8 affected mostly glia as indicated by a loss of glial-marker immunoreactivity. A frameshift mutation in the GFP gene reduced overall toxicity for serotypes 1, 5 and 6, but not 7 and 8 suggesting that the toxicity was not solely due to the overexpression of GFP. Collectively, a differential tropism and toxicity was observed among the AAV serotypes on primary cortical cultures with an overall preferential glial transduction and toxicity.     

Exploration, distraction, and habituation in rats reared in isolation

Rats reared in isolation have been reported to show increased motor activity; the purpose of the present experiment was to establish whether they also show enhanced exploratory and orienting responses. Rats were reared in isolation or in social groups from Day 20 to Day 45. Subgroups of each rearing condition were either left undisturbed, received daily handling, or received daily handling and were given objects in their cages. From Day 45 all the rats were rehoused in groups of 6, and testing began at Day 73. In a 1st test exploration was measured by the number of contacts with objects placed in the home cage; and a 2nd test exploration was measured by responses to a holeboard; and in a 3rd test orienting was measured by the distraction produced by the presentation of a tone. When tested in novel situations, in contrast to their enhanced motor activity, isolates showed reduced exploration and orienting. This may have been due to a discrepancy between their adaptation level (established during rearing) and their current level of sensory input. In all the tests the isolates showed normal habituation, both within sessions and between sessions. An inability to habituate is not, as has been claimed, a general characteristic of isolates.     

Communication, conflict, and psychological distance in nondistressed, clinic, and divorcing couples

This study compared communication patterns and conflicts over psychological distance in 25 nondistressed couples, 15 clinic couples, and 22 divorcing couples. Data consisted of questionnaire reports completed independently by husbands and wives. The two distressed groups, compared with nondistressed couples, had less mutual constructive communication, more avoidance of communication, more demand/withdraw communication, and more conflict over psychological distance in their relationships. In addition, the divorcing group had less mutual constructive communication than the clinic group and evidenced a trend for more conflict over psychological distance than the clinic group. Consistent with past research, wife demand/husband withdraw communication was more likely across all groups than husband demand/wife withdraw communication. Results are discussed in terms of skills deficits and incompatability models of marital discord.     

Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis

Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37 degrees C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the five mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial oxygen uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported oxygen uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the two models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. The results demonstrate 1) differential enzyme lability within the mitochondrial inner membrane, 2) a connection between severity of acidosis and the degree of enzyme activity loss, and 3) the usefulness of simple tissue autolysis as an analogue of in situ myocardial ischemia.     

Advances in asthma, allergy mechanisms, and genetics in 2006

This review discusses the main advances in animal models of allergic airway disease and genetics of asthma and allergy published in the Journal in 2006. This work highlighted and extended what has become the central dogma of allergic pathogenesis by highlighting the mechanisms involved in inducing a T(H)2 response and in determining how T(H)2 cytokines induce the allergic airway disease phenotype. By so doing, they have identified a considerable number of potential therapeutic targets. Genetic analyses, on the other hand, revealed novel, potentially important candidate genes, confirmed known ones, and refined our understanding of the putative role played by others, sometimes positively, sometimes negatively. These data reiterate allergic inflammation is a classic complex genetic disease-that is, a disorder in which multiple and distinct genetic determinants variously interact with one another and with relevant environmental exposures to result in clinical phenotypes that, although superficially similar, involve distinct genetic pathways and represent the outcome of distinct pathogenetic mechanisms.     

Guilt,fear, submission,and empathy in depression

BACKGROUND: This study compares self-focused motivations (fear of negative evaluation, social comparison, and fear of envy) and other-focused motivations (empathy and interpersonal guilt) in submissive behavior and depression. METHODS: The Beck Depression Inventory, Submissive Behavior Scale, Fear of Negative Evaluation Scale, Social Comparison Scale, Interpersonal Guilt Questionnaire, and Interpersonal Reactivity Inventory were administered to 50 patients hospitalized for depression and 52 students. RESULTS: Depressed patients were significantly higher in survivor guilt, omnipotent responsibility guilt, submissive behavior, fear of negative evaluation, fear of envy, and empathic distress, and lower in social comparison. LIMITATIONS: This research was limited in that it was a correlational study. CONCLUSIONS: This study suggests that altruistic concern about others may be an important factor in depression and submissive behavior. Evolutionary implications of these findings are discussed.     

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.     

Motor nerve conduction in 47, XXY and 48, XXYY males, and 47, XXX and 45, X females

Measurements were made of the maximum motor nerve conduction in the median and ulnar nerves of the right forearm for the four sex chromosomally abnormal groups 47, XXY and 48, XXYY males, 47, XXX and 45, X females. The results obtained were compared with male and female control groups (a) from the general population and (b) from a subnormality hospital. No significant differences were detected between the corresponding results for 47, XXY males and subnormal males. The results for the 47, XXY males were different from those for normal and subnormal females, except in the case of motor conduction in the median nerve for the subnormal female group. There is a suggestion of marked differences in motor conduction and distal latency in 48, XXYY males when compared to the two male control groups. 47, XXX females showed significant differences in motor conduction and distal latency when compared to normal females, but not when compared to subnormal females. No significant differences were detected between 45, X females and normal females for any of the variables measured.     

Global and local processing in Williams syndrome, autism, and Down syndrome: perception, attention, and construction

Global and local processing was studied in Williams Syndrome (WS), autism (AS), and Down Syndrome (DS) using perception, attention, and construction tasks. Past research has suggested an abnormal bias toward global processing in DS and, in contrast, an abnormal local bias in both WS and AS. Until now, no study has investigated whether the local processing bias in WS and AS has a different or similar underlying cause. Findings here suggest a common underlying mechanism, namely a bias in attention toward local processing. Results also indicate a global bias in attention in DS. This study finds no evidence to support predictions of the hierarchical deficit theory (Mottron & Belleville, 1993) as an explanation of hierarchical processing deficits in AS or DS, but does find support for hierarchical deficit theory in a subset of WS individuals. This study finds evidence of cognitive heterogeneity in WS, consistent with Porter and Coltheart (2005).     

Malignancy in scars, chronic ulcers, and sinuses

A collection of 44 cases of malignancy in scars, chronic ulcers, and sinuses, included the following predisposing lesions: a 20-year-old sinus from ischial bursitis, a 23-year-old bed sore, a congenital gumma about 50 years old, three burn scars (average age of scar 56 years), 11 sinuses from chronic osteomyelitis, and 27 chronic ulcers of the leg. The osteomyelitis cases included two rapidly fatal sarcomas, one in a sinus present for 16 years, the other in a 20-year-old sinus. The remaining tumours in this group were squamous carcinomas that developed in sinuses with an average duration of 37 years. In the cases of varicose ulcer, the ulcer had been present on the average for 21 years before the onset of malignancy. One patient in this group, with an ulcer not known to be more than five years old, developed a sarcoma that was fatal in six months. The biopsy diagnosis was difficult in 17 cases, including one of the cases of sarcoma. The difficulty was greatest in cases of osteomyelitis. The conditions discussed are now known as `Marjolin's ulcer'. In the present series, the degree of malignancy in tumours arising in scars may be low but the malignancy of tumours arising in chronic ulcers and sinuses may be high.     

Global and Local Processing in Williams Syndrome,Autism, and Down Syndrome: Perception,Attention, and Construction

Global and local processing was studied in Williams Syndrome (WS), autism (AS), and Down Syndrome (DS) using perception, attention, and construction tasks. Past research has suggested an abnormal bias toward global processing in DS and, in contrast, an abnormal local bias in both WS and AS. Until now, no study has investigated whether the local processing bias in WS and AS has a different or similar underlying cause. Findings here suggest a common underlying mechanism, namely a bias in attention toward local processing. Results also indicate a global bias in attention in DS. This study finds no evidence to support predictions of the hierarchical deficit theory (Mottron & Belleville, 1993) as an explanation of hierarchical processing deficits in AS or DS, but does find support for hierarchical deficit theory in a subset of WS individuals. This study finds evidence of cognitive heterogeneity in WS, consistent with Porter and Coltheart (2005).     

Antigen recognition in Filipinos, Japanese, Chinese, and Caucasians

Allergic Chinese, Japanese, Filipinos, and Caucasian groups were compared and contrasted according to their skin test reactivity to pollens of grasses and trees. If a subject reacted to grasses, there was a significantly greater risk of reaction to trees (P less than .0005). The risk was profoundly greater in the three non-Caucasian groups (Filipino, Chinese, and Japanese) compared with the Caucasian group (P less than .0005). Reactivity to grass appeared to amplify the risk of reaction to trees. This effect was particularly striking in the non-Caucasian groups. In groups that did not react to grasses, there was no difference between races in reactivity to trees. The non-Caucasian races did not demonstrate significant differences in their reaction to grasses. All three non-Caucasian groups appear to be more sensitive than the matched Caucasians to cedar, cypress, and juniper.     

Trials, tribulations, and trends in tumor modeling in mice

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated in clinical trials. Inherent limitations of tumor models coupled with the advent of new therapeutic targets reinforce need for careful attention to design, conduct, and stringent selection of in vivo and ex vivo endpoints. Preclinical efficacy testing for anti-tumor therapies should progress through a series of models of increasing sophistication that includes incorporation of genetically engineered animals, and orthotopic and combination therapy models. Pharmacology and safety testing in tumor-bearing animals may also help to improve predictive value of these models for clinical efficacy. Trends in bioinformatics, genetic refinements, and specialized imaging techniques are helping to maintain mice as the most scientifically and economically powerful model of malignant neoplasms.     

Pets, parental atopy, and asthma in adults

BACKGROUND: Studies of exposure to pets and the risk of asthma have provided conflicting results. OBJECTIVE: We conducted a population-based incident case-control study to assess the relationship of current and previous pet keeping with the risk of adult-onset asthma. We also investigated whether genetic propensity as a result of parental atopy modifies these relations. METHODS: From the source population of 441,000 inhabitants of a geographically defined area in South Finland, we systematically recruited, during a 2.5-year period, all new cases of asthma in 21- to 63-year-old adults and randomly selected control subjects. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and a control series of 932 control subjects. Information on current and past exposure to hairy pets was collected by using a self-administered questionnaire. RESULTS: In logistic regression analysis the risk of asthma was lower among subjects with pets during the past 12 months (adjusted odds ratio [OR], 0.74; 95% confidence interval [CI], 0.57-0.96) but higher among subjects with pets more than 12 months previously (adjusted OR, 1.39; 95% CI, 1.05-1.84). Parental atopy increased the risk of asthma (OR, 1.88; 95% CI, 1.47-2.41), but there was no interaction between parental atopy and pet exposure. CONCLUSIONS: The present results are consistent with the hypothesis that both keeping furry pets and parental atopy increase the risk of asthma development in adulthood. Parental atopy does not modify the effects of pet exposure. The negative association between current pets and the risk of asthma is consistent with selective avoidance of these pets by symptomatic individuals.