Resolution of genetic and cultural inheritance in twin families by path analysis: application to HDL-cholesterol.

A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.     

Genetic analysis of the structure of predisposition to diabetes mellitus. III. Genetic heterogeneity of diabetes mellitus with different ages of onset

The results of genetical-epidemiological analysis of the three conventional forms of diabetes mellitus (DM) differentiated for age-at-onset are presented (the form I - from 0 to 29 y. the form II - from 30 to 59 y. the form III - 60 y. and older). The estimates of heritability of liability to the forms I, II and III of DM were 0.57, 0.70 and 0.65, respectively. It was shown that genetic components of the forms I and II are virtually different: genetic correlation between these forms was rA = 0.216 +/- 0.203, which is statistically insignificant. These data support the hypothesis assuming genetic independence of juvenile and adult forms of DM. On the other hand, the forms II and III were found to have an essential number of genes in common: genetic correlation was rA = 0.495 +/- 0.134, being significant at the 5% level. Thus, the forms II and III of DM are not to be considered as two genetically distinct diseases. The low recurrence risks of the form I for siblings (not more than 3.6%) allow to reject the hypothesis of simple monogenic inheritance of juvenile DM and to propose multifactorial nature of the disease.     

SPECIES RICHNESS WITHIN FAMILIES OF FLOWERING PLANTS

Variation in species and genus richness among families of flowering plants was examined with respect to four classification variables: geographical distribution, growth form, pollination mode, and dispersal mode. Previous studies have estimated rates of species proliferation from age and contemporary diversity. Here we found that the earliest appearances in the fossil record are correlated with contemporary familial species richness, abundance in the fossil record, and the independent variables considered in this analysis. Thus, we believe that the fossil record does not provide reasonable estimates of the ages of families and that the rate of species proliferation cannot be calculated from such data without bias. Accordingly, our subsequent analyses were based on contemporary species richness of families. Although the classification variables were interrelated, each made largely independent contributions to familial species richness. Cosmopolitan families were 5.6 times more species-rich than strictly tropical families and 35 times more species-rich than strictly temperate families. Families including both herbaceous and woody growth forms were 5.7 and 14 times more species-rich than families with either growth form alone. Although animal pollination was significantly associated with elevated familial species richness, the effect was statistically weak. The most prominent effect was that families with both abiotic and biotic dispersal had more than 10 times as many species as families with either dispersal mode alone. Our analyses also revealed that families having both dispersal modes were more likely to have several growth forms, suggesting that evolutionary flexibility of morphology may be generalized over diverse aspects of life history. These results do not support the idea that pollination and dispersal by animals were primarily responsible for the tremendous proliferation of angiosperm species, either by producing population structures conducive to speciation or by applying selection for diversification. Instead, the importance of varied dispersal mode, growth form, and climate zone in predicting high familial species richness suggests that a capacity to diversify morphologically and physiologically may have been primarily responsible for high rates of species proliferation in the flowering plants.     

Homeostatic responses to caloric restriction: influence of background metabolic rate.

The biological responses to caloric restriction (CR) are generally examined in rats with elevated metabolic rates due to being housed at ambient temperatures (T(a)) below the zone of thermoneutrality. We determined the physiological and behavioral responses to 2 wk of 30-40% CR in male FBNF1 rats housed in cool (T(a) = 12 degrees C) or thermoneutral (TMN; T(a) = 30 degrees C) conditions. Rats were instrumented with telemetry devices and housed continuously in home-cage calorimeters for the entire experiment. At baseline, rats housed in cool T(a) had reduced rate of weight gain; thus a mild CR (5%) group at thermoneutrality for weight maintenance was also studied. Rats housed in cool T(a) exhibited elevated caloric intake (cool = 77 +/- 1; TMN = 54 +/- 2 kcal), oxygen consumption (Vo(2); cool = 9.9 +/- 0.1; TMN = 5.5 +/- 0.1 ml/min), mean arterial pressure (cool = 103 +/- 1; TMN = 80 +/- 2 mmHg), and heart rate (cool = 374 +/- 3; TMN = 275 +/- 4 beats/min). Cool-CR rats exhibited greater CR-induced weight loss (cool = -62 +/- 3; TMN = -42 +/- 3 g) and reductions in Vo(2) (cool = -2.6 +/- 0.1; TMN = -1.5 +/- 0.1 ml/min) but similar CR-induced reductions in heart rate (cool = -59 +/- 1; TMN= -51 +/- 7 beats/min). CR had no effect on arterial blood pressure or locomotor activity in either group. Unexpectedly, weight maintenance produced significant reductions in Vo(2) and heart rate. At thermoneutrality, a single day of refeeding effectively abolished CR-induced reductions in Vo(2) and heart rate. The results reveal that rats with low or high baseline metabolic rate exhibit comparable compensatory reductions in Vo(2) and heart rate and suggest that T(a) can be used to modulate the metabolic background on which the more prolonged effects of CR can be studied.     

Association between the Val66Met polymorphism of brain-derived neurotrophic factor gene and schizophrenia in Russians

Recent studies have demonstrated a role of the brain-derived neurotrophic factor (BDNF) in schizophrenia. An association between the Val66Met BDNF polymorphism has been reported but the results of different studies are inconsistent. An aim of the present article is to study the allele and genotype distribution in patients with schizophrenia (783) and mentally healthy controls (633). No statistically significant between-group differences have been found. When the group of patients has been stratified by sex and form of schizophrenia, the higher frequency of the Val/Val genotype is observed in the subgroup of men with continuous (chronic) schizophrenia as compared to men with attack-like form (p = 0.047). Clinical symptoms assessed with the PANSS were more severe in male patients with the Val/Val genotype. The Val66Met polymorphism was not associated with forms of schizophrenia or clinical symptoms in female patients. The results obtained suggest that the association between the BDNF gene and schizophrenia may be related to sex and clinical heterogeneity of disease. The Val/Val genotype is associated with severer form of schizophrenia in men.     

Anticipation or ascertainment bias in schizophrenia? Penrose's familial mental illness sample.

Several studies have observed anticipation (earlier age at onset [AAO] in successive generations) in familial schizophrenia. However, whether true anticipation or ascertainment bias is the principal originating mechanism remains unclear. In 1944 L. S. Penrose collected AAO data on a large, representative sample of familial mental illness, using a broad ascertainment strategy. These data allowed examination of anticipation and ascertainment biases in five two-generation samples of affected relative pairs. The median intergenerational difference (MID) in AAO was used to assess anticipation. Results showed significant anticipation in parent-offspring pairs with schizophrenia (n = 137 pairs; MID 15 years; P = .0001) and in a positive control sample with Huntington disease (n = 11; P = .01). Broadening the diagnosis of the schizophrenia sample suggested anticipation of severity of illness. However, other analyses provided evidence for ascertainment bias, especially in later-AAO parents, in parent-offspring pairs. Aunt/uncle-niece/nephew schizophrenia pairs showed anticipation (n = 111; P = .0001), but the MID was 8 years and aunts/uncles had earlier median AAO than parents. Anticipation effects were greatest in pairs with late-AAO parents but remained significant in a subgroup of schizophrenia pairs with early parental AAO (n = 31; P = .03). A small control sample of other diseases had MID of 5 years but no significant anticipation (n = 9; P = .38). These results suggest that, although ascertainment-bias effects were observed in parent-offspring pairs, true anticipation appears to be inherent in the transmission of familial schizophrenia. The findings support investigations of unstable mutations and other mechanisms that may contribute to true anticipation in schizophrenia.     

Causal analysis of the variability of IgA, IgG, and IgM immunoglobulin levels

The interindividual variability of IgA, IgG, and IgM immunoglobulin levels was studied using path analysis in a northeastern Brazilian sample (nuclear families) to determine the genetic and/or environmental causes of their variation. The path analysis model decomposes the phenotype into genetic causes (autosomal and X-chromosome-linked genes) and environmental causes. A significant familial aggregation, mainly resulting from autosomal components, was detected for the 3 immunoglobulin levels. The values of genetic heritability were h2 = 0.410 +/- 0.030 for IgA, h2 = 0.617 +/- 0.020 for IgG, and h2 = 0.540 +/- 0.023 for IgM, and the values for environmental-cultural heritability were c2 = 0.085 +/- 0.034 for IgA, c2 = 0.084 +/- 0.027 for IgG, and c2 = 0.023 + 0.023 for IgM. Our results did not show a heritable component resulting from X-chromosome-linked genes on IgM levels, as suggested by some studies (Wood et al. 1969; Grundbacher 1972; Purtilo and Sullivan 1979). Some additional results were that (1) age and IgA concentration were positively correlated, with IgA level increasing gradually from childhood to adulthood (p < 0.001); (2) sex and the age X sex interaction act on IgG concentration (p < 0.01); (3) age and IgM concentration are correlated (with children presenting lower levels than adults, especially in males, p < 0.01); and (4) a significant association exists between sex and IgM level (with females presenting higher levels than males, p < 0.001).     

Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.     

Metabolic rate in the whip-spider, Damon annulatipes (Arachnida: Amblypygi)

Metabolic rate estimates as well as a measure of their repeatability and response to laboratory acclimation are provided for the amblypygid Damon annulatipes (Wood). This species (mean +/- S.E. mass: 640+/-66 mg) shows continuous gas exchange, as might be expected from its possession of book lungs, and at 21 degrees C has a metabolic rate of 30.22+/-2.87 microl CO2 h(-1) (approximately 229.6+/-21.8 microW, R.Q. = 0.72). The intraclass correlation coefficient (r=0.74-0.89) indicated substantial repeatability in metabolic rate which did not change with laboratory acclimation over a period of 2 weeks. By contrast, absolute metabolic rate declined by c. 16-33%, although this was not a consequence of changes in mass (which were non-significant over the same period). Rather, it appears that a reduction in overall stress or activity in the laboratory might have been responsible for the decline in mass-independent metabolic rate. At the intraspecific level, metabolic rate scaled as microW = 342 M(0.857), where mass is in grams. Metabolic rates of this species are in keeping with its sedentary behaviour such that for a given body size they are lower than those of most arthropods (spiders and insects), higher than the very sedentary ticks, and equivalent to scorpions. These findings have implications for the understanding of the evolution of metabolic rates in arthropods.     

Risk of cerebrovascular disease incidence in the cohort of Mayak production association workers first employed during 1948-1958

Incidence of cerebrovascular diseases (CVD) has been studied in a cohort of 12210 workers first employed at one of the main plants (reactors, radiochemical or plutonium) of the Mayak nuclear facility during 1948-1958 and followed up to the end of 2000. Information on external gamma doses is available for virtually all (99.9%) of these workers; the mean (+/- one standard deviation) total gamma dose was 0.91 +/- 0.95 Gy (99% percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for women. Plutonium body burden was measured only for 30.0% of workers. Amongst those monitored, the mean (+/- standard deviation) cumulative liver dose from plutonium alpha exposure was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81 +/- 4.60 Gy (99% percentile 15.95 Gy) for women 4418 cases (first diagnosis) of CVD were identified in the studied cohort. A statistically significant increasing trend in CVD incidence with total external gamma dose was revealed after adjustment for non-radiation factors and internal exposure from incorporated plutonium-239. Excess relative risk per Gy was 0.464 (95% confidence interval 0.360-0.567). Incidence of CVD was statistically significantly higher for the workers chronically exposed to external gamma rays at a dose above 1.0 Gy A statistically significant increasing trend in CVD incidence with internal liver dose from plutonium alpha exposure was observed after adjustment for non-radiation factors and external exposure. ERR per Gy was 0.155 (95% confidence interval 0.075-0.235). CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy, although the trend estimates differed between workers at different plants. The incidence risk estimates for external radiation are generally compatible with estimates from the study of Chernobyl clean-up workers, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.     

pH-dependent forms of the ferryl haem in myoglobin peroxide analysed by variable-temperature magnetic circular dichroism.

The reaction product of myoglobin and H2O2 exists in two different forms according to the external pH. Varied-temperature magnetic-circular dichroism (m.c.d.) spectroscopy demonstrates that both contain the oxyferryl ion Fe(IV) = O. Alkaline myoglobin peroxide has often been used as a model for oxidized intermediates in the catalytic cycles of haem-containing peroxidases, but absorption and m.c.d. spectra show that the acid form is much more closely related to species such as horeradish peroxidase Compound II. The differences are tentatively ascribed to ionization of the proximal histidine ligand in alkaline myoglobin peroxide. It is also shown that the m.c.d. method allows an estimate of the zero-field splitting parameter of both forms, values of D = 28.0 +/- 3 cm-1 and 35.0 +/- 5 cm-1 being obtained for the alkaline and acid forms respectively.     

NMR study of the alkaline isomerization of ferricytochrome c

The pH-induced isomerization of horse heart cytochrome c has been studied by 1H NMR. We find that the transition occurring in D2O with a pKa measured as 9.5 +/- 0.1 is from the native species to a mixture of two basic forms which have very similar NMR spectra. The heme methyl peaks of these two forms have been assigned by 2D exchange NMR. The forward rate constant (native to alkaline cytochrome c) has a value of 4.0 +/- 0.6 s-1 at 27 degrees C and is independent of pH; the reverse rate constant is pH-dependent. The activation parameters are delta H not equal to = 12.8 +/- 0.8 kcal.mol1, delta S not equal to = -12.9 +/- 2.0 e.u. for the forward reaction and delta H not equal to = 6.0 +/- 0.3 kcal.mol-1, delta S not equal to = -35.1 +/- 1.3 e.u. for the reverse reaction (pH* = 9.28). delta H degree and delta S degree for the isomerization are 6.7 +/- 0.6 kcal.mol-1 and 21.9 +/- 1.0 e.u., respectively.     

Correction: Dynamic Changes of Post-Translationally Modified Forms of CXCL10 and Soluble DPP4 in HCV Subjects Receiving Interferon-Free Therapy

Serum levels of the interferon (IFN)-stimulated chemokine CXCL10 are increased during chronic HCV infection and associate with outcome of IFN-based therapy. Elevated levels of NH2-terminal truncated CXCL10 (3-77aa), produced by DPP4 cleavage, negatively associate with spontaneous clearance of acute HCV infection and sustained virological response (SVR) with IFN-based therapy for chronic infection. The association of different CXCL10 forms and DPP4 with outcome during IFN-free HCV therapy has not been examined. Using novel Simoa assays, plasma was analyzed from HCV genotype-1 (GT1) subjects who relapsed (n = 11) or achieved SVR (n = 10) after sofosbuvir and ribavirin (SOF/RBV) treatment, and from SOF/RBV relapsers who achieved SVR with a subsequent SOF/ledipasvir regimen (n = 9). While the NH2-truncated form of CXCL10 was elevated in HCV infection relative to healthy controls, pre-treatment plasma concentrations of CXCL10 forms failed to stratify subjects based on treatment outcome to IFN-free regimens. However, a trend (statistically non-significant) towards elevated higher levels of total and long CXCL10 was observed pre-treatment in subjects who relapsed. All forms of CXCL10 decreased rapidly following treatment initiation and were again elevated in subjects who experienced HCV relapse, indicating that CXCL10 production may be associated with active viral replication. While soluble DPP4 (sDPP4) and NH₂-truncated CXCL10 concentrations were highly correlated, on-treatment sDPP4 levels and activity declined more slowly than CXCL10, suggesting differential regulation. Conclusion: These data suggest post-translationally modified forms of CXCL10 will not support the prediction of treatment outcome in HCV GT1 subjects treated with SOF/RBV.     

Embryos and culture cells: a model for studying the effect of progesterone

A positive association between P4 concentration and initial bovine embryo survival has been reported. The objective of this study was to establish two coculture systems as a model to study the influence of progesterone on the initial bovine embryo development. Granulosa cells (GC) or bovine oviduct epithelial cells (BOECs) were used at the base of embryo culture medium microdroplets (TCM199 and 10% of superovulated oestrus cow serum, (SOCS)) supplemented or not with progesterone (P4, 33.4 ng mL(-1)) and/or a progesterone receptor antagonist (onapristone, OP, 2.2x10(-5)M). Presumptive zygotes were transferred to monolayers after in vitro maturation and fertilization of bovine oocytes with thawed swim-up selected sperm. Embryo development was carried out according to the following groups: experiment 1, BOEC (n=378) and BOEC plus OP (n=325); experiment 2, GC (n=514); GC plus OP (n=509); BOEC (n=490); BOEC plus P4 (n=500); BOEC plus P4 and OP (n=502). Embryos were checked for cleavage at day 2 and for stage development between days 8 and 12 of culture. In experiment 1, no differences (P>0.05) were identified between BOEC and BOECOP groups for embryo rates of development, quality or developmental stages. Also in experiment 2, no differences were found in embryo rates of development, quality or developmental stages between embryos cultured under the two coculture systems when no supplementation was added. Embryo development rates were not affected by OP presence in GCOP group. However, P4 negatively affected Day 8 (D8) embryo development rates in BOEC system (BOECP4=16.8+/-2.6% vs. BOEC=23.7+/-1.7%, P=0.02). This negative effect was abolished when P4 antagonist (OP) was added to the culture medium. BOEC supplementation with P4 also induced a delay on embryo development at D8 as confirmed by a lower development score (BOECP4=3.0+/-1.4 vs. GC=3.4+/-0.1, GCOP=3.5+/-0.1, BOEC=3.4+/-0.1 and BOECP4OP=3.5+/-0.1; P<0.05). These results demonstrate that OP supplementation had no harmful effect on embryo development either in granulosa, where P4 is naturally synthesised, or in BOEC coculture systems. Also we can not confirm a direct association between high P4 concentrations and embryo survival during early stages, although P4 may influence early embryo development through different mechanisms mediated by the type of cells present.     

Protein synthesis in the liver of Bufo marinus: cost and contribution to oxygen consumption

While many estimates of the contribution of protein synthesis to metabolic rate exist for a variety of animals, most rely on theoretical costs of protein synthesis. The limitations of this approach are that theoretical costs depend upon variable estimates of ATP cost per peptide bond. In addition, they do not take into account the fact that there are protein-specific pre- and post-translational costs. By inhibiting, protein synthesis with cycloheximide and measuring the resultant decrease in oxygen consumption, we have measured the actual cost of protein synthesis and its contribution to metabolic rate in an in vitro system of tissue slices from Bufo marinus. Such measurements exist for endotherms, but there are few such measurements for ectotherms, and none have been done previously for amphibians. The cost of protein synthesis in liver slices from B. marinus was 7.32+/-1.19 mmol O2 x g(protein)(-1) (x +/- SE, n = 48) and protein synthesis accounted for 12% of the total metabolic rate of this tissue. This cost is comparable to values measured for other ectotherms although the contribution of protein synthesis to metabolic rate is at the lower end of the range of estimates for other ectotherms.     

Childhood exposure to ionizing radiation to the head and risk of schizophrenia

While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.     

Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia

Plasma lipoprotein concentration, composition, and size were evaluated in two common familial forms of hypertriglyceridemia and compared with those in normal subjects. The very low density lipoproteins (VLDL) were triglyceride-enriched in familial hypertriglyceridemia (triglyceride/apoprotein B ratio: 25.7 +/- 8.9) as compared to normal (9.6 +/- 12.2, P < 0.001) or familial combined hyperlipidemia (9.7 +/- 3.3, P < 0.001). The diameter of VLDL was larger in familial hypertriglyceridemia (3.27 +/- 0.28 pm) than in familial combined hyperlipidemia (2.87 +/- 0.16 pm, P < 0.02). Although in familial hypertriglyceridemia VLDL tended to be larger, and in familial combined hyperlipidemia VLDL tended to be smaller than normal (3.08 +/- 0.48 pm), neither of these differences were significant. While VLDL was normally distributed in the control population, the size was skewed to larger particles in familial hypertriglyceridemia with fewer small particles (P < 0.05) and skewed to smaller particles in familial combined hyperlipidemia with fewer large particles (P < 0.05). VLDL was reciprocally related to low density lipoproteins (LDL) in familial combined hyperlipidemia (r = -0.80 to -0.87) suggesting that the concentrations of these individual lipoprotein groups were somehow interrelated. There was no significant relationship between these two lipoprotein classes in familial hypertriglyceridemia or in normals. In familial combined hyperlipidemia, the apoprotein A-I/A-II ratio was below normal (P < 0.01) suggestive of low HDL(2) levels. This change in apoprotein composition was independent of VLDL or LDL concentration. In familial hypertriglyceridemia, high density lipoprotein (HDL) cholesterol was reduced (33% below mean normal) and HDL triglyceride was increased (by 46%), while the concentration of apoA-I and apoA-II was normal. VLDL triglyceride was inversely related to HDL cholesterol in familial hypertriglyceridemia (r = -0.74, P < 0.005), but not in familial combined hyperlipidemia. The large, triglyceride-enriched VLDL observed in familial hypertriglyceridemia is compatible with the reported increase in VLDL triglyceride synthesis seen in this disorder. The increase in VLDL apoprotein B synthesis previously reported in familial combined hyperlipidemia was associated with VLDL of normal composition. The changes in HDL cholesterol in these two disorders might reflect exchange of triglyceride between VLDL and HDL or could be related to transfer of surface components during the catabolism of VLDL. The reciprocal relationship between various components of VLDL and LDL seen in familial combined hyperlipidemia, but not in familial hypertriglyceridemia or in normal subjects, might provide some insight into the pathological abnormalities in these disorders. The differences between these two common familial forms of hypertriglyceridemia provide further support that they are distinct entities.-Brunzell, J. D., J. J. Albers, A. Chait, S. M. Grundy, E. Groszek, and G. B. McDonald. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.     

Behavioral inference of diving metabolic rate in free-ranging leatherback turtles

Good estimates of metabolic rate in free-ranging animals are essential for understanding behavior, distribution, and abundance. For the critically endangered leatherback turtle (Dermochelys coriacea), one of the world's largest reptiles, there has been a long-standing debate over whether this species demonstrates any metabolic endothermy. In short, do leatherbacks have a purely ectothermic reptilian metabolic rate or one that is elevated as a result of regional endothermy? Recent measurements have provided the first estimates of field metabolic rate (FMR) in leatherback turtles using doubly labeled water; however, the technique is prohibitively expensive and logistically difficult and produces estimates that are highly variable across individuals in this species. We therefore examined dive duration and depth data collected for nine free-swimming leatherback turtles over long periods (up to 431 d) to infer aerobic dive limits (ADLs) based on the asymptotic increase in maximum dive duration with depth. From this index of ADL and the known mass-specific oxygen storage capacity (To(2)) of leatherbacks, we inferred diving metabolic rate (DMR) as To2/ADL. We predicted that if leatherbacks conform to the purely ectothermic reptilian model of oxygen consumption, these inferred estimates of DMR should fall between predicted and measured values of reptilian resting and field metabolic rates, as well as being substantially lower than the FMR predicted for an endotherm of equivalent mass. Indeed, our behaviorally derived DMR estimates (mean=0.73+/-0.11 mL O(2) min(-1) kg(-1)) were 3.00+/-0.54 times the resting metabolic rate measured in unrestrained leatherbacks and 0.50+/-0.08 times the average FMR for a reptile of equivalent mass. These DMRs were also nearly one order of magnitude lower than the FMR predicted for an endotherm of equivalent mass. Thus, our findings lend support to the notion that diving leatherback turtles are indeed ectothermic and do not demonstrate elevated metabolic rates that might be expected due to regional endothermy. Their capacity to have a warm body core even in cold water therefore seems to derive from their large size, heat exchangers, thermal inertia, and insulating fat layers and not from an elevated metabolic rate.     

Crystal structure and morphology of poly(12-dodecalactone)

Poly(12-dodecalactone) (PDDL) crystals in the form of chain-folded lamellae were prepared by isothermal crystallization from a 1-hexanol solution. The lozenge-shaped crystals with and without spiral growth have been studied by transmission electron microscopy and atomic force microscopy. Wide-angle X-ray diffraction data, obtained from PDDL lamellae sedimented to form oriented mats and annealed solvent-cast film, were supplemented with morphological and structural data from electron microscopy. PDDL crystallizes as an orthorhombic form with a P2(1)2(1)2(1) space group and lattice constants of a = 0.746 +/- 0.001 nm, b = 0.500 +/- 0.001 nm, and c (chain axis) = 3.281 +/- 0.003 nm. There are two chains per unit cell, which existed in an antiparallel arrangement. The fiber repeat distance is appropriate for an all-trans backbone conformation for the straight stems. Molecular packing of this structure has been studied in detail, taking into account both diffraction data and energy calculations. The setting angles, with respect to the a axis, were +/-43 degrees for the corner and center chains according to intensity measurements and structure factor calculations. The optimized shift along the crystallographic c axis is 0.1c (0.328 nm). A final model was obtained to yield R = 0.180 with X-ray diffraction data and R = 0.162 with electron diffraction data. A brief comparison is also made with related polymer structures.