Exon skipping in the sterol 27-hydroxylase gene leads to cerebrotendinous xanthomatosis

We report a new mutation in the sterol 27-hydroxylase (CYP 27) gene in a Dutch family with cerebrotendinous xanthomatosis: a G→A transition in the splice donor site in intron 4. This mutation leads to skipping of exon 4, resulting in a loss of 66 amino acids in the CYP 27 enzyme molecule. Received: 15 March 1997 / Accepted: 26 March 1997     

Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat.

Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D.     

Male-Driven Differences in Chimpanzee (<Emphasis Type="Italic">Pan troglodytes</Emphasis>) Population Genetic Structure Across Three Habitats in Cameroon and Nigeria

Complex ecological pressures affect the social dynamics of many primate species, but it is unclear how they affect primate speciation. Molecular tools are often used to answer questions about the evolutionary histories and social systems of primates. Mitochondrial DNA (mtDNA), in particular, is frequently used to answer many of these questions, but because it is passed from mothers to offspring it reveals only the histories of females. In many species, including chimpanzees, females generally disperse from their natal groups while males are philopatric, and thus differences in dispersal patterns likely leave different signatures in the genome. We previously analyzed samples from 187 unrelated male and female chimpanzees in Nigeria and Cameroon using 21 autosomal microsatellites and mtDNA sequences. Here, we examine the contributions of males and females in shaping the genetic history of these chimpanzees by genotyping a subset of 56 males at 12 Y-chromosome microsatellites. We found that Y-chromosome population structure differed from the results of analysis of mtDNA haplotypes. The results also revealed that males in rainforest habitats (Guinean and Congolian rainforests) are more closely related to one another than those inhabiting the savanna-woodland mosaic ecotone in central Cameroon. In contrast, the pattern of female relatedness did not differ across habitats. We hypothesize that these differences in population structure and patterns of relatedness among males in different habitat types may be due to differences in the community dynamics of chimpanzees in the ecotone vs. rainforests, and that these factors contribute to making Cameroon an engine of diversification for chimpanzees. Broadly, these results demonstrate the importance of habitat variation in shaping social systems, population genetics, and primate speciation.     

Female sex steroid induced epithelial changes in the gallbladder of the ovariectomized Syrian hamster.

Ovariectomized Syrian hamsters treated by female sex steroids during a 1-month period show gallbladder surface epithelial changes in the fundic area consistent with apical bulging and decapitations of the epithelial cells. These events were detected in the infundibulum and the fundic or body regions of estrogen- and estrogen+progesterone-treated hamsters. In control hamsters, these events were restricted to the region in the vicinity of the bile duct. Following steroid treatment, intraluminal deposits detected resembled Ca-bilirubinate deposits described in previous studies while decapitations are similar to endometrial epithelium changes associated with hormonal physiological changes or treatments. Moreover some small electron-dense deposits are comparable to those found in human cholesterol gallstones. This report indicates that, besides an alteration in bile composition, cell fragments originating from the surface epithelium of the bile duct and/or of the gallbladder mucosal epithelium could participate in gallstone nucleation.     

Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

The next step in biology: A periodic table?

Systems biology is an approach to explain the behaviour of a system in relation to its individual components. Synthetic biology uses key hierarchical and modular concepts of systems biology to engineer novel biological systems. In my opinion the next step in biology is to use molecule-to-phenotype data using these approaches and integrate them in the form a periodic table. A periodic table in biology would provide chassis to classify, systematize and compare diversity of component properties vis-a-vis system behaviour. Using periodic table it could be possible to compute higher-level interactions from component properties. This paper examines the concept of building a bio-periodic table using protein fold as the fundamental unit.     

Alpine vascular plant species richness: the importance of daily maximum temperature and pH

Species richness in the alpine zone varies dramatically when communities are compared. We explored (i) which stress and disturbance factors were highly correlated with species richness, (ii) whether the intermediate stress hypothesis (ISH) and the intermediate disturbance hypothesis (IDH) can be applied to alpine ecosystems, and (iii) whether standing crop can be used as an easily measurable surrogate for causal factors determining species richness in the alpine zone. Species numbers and standing crop were determined in 14 alpine plant communities in the Swiss Alps. To quantify the stress and disturbance factors in each community, air temperature, relative air humidity, wind speed, global radiation, UV-B radiation, length of the growing season, soil suction, pH, main soil nutrients, waterlogging, soil movement, number of avalanches, level of denudation, winter dieback, herbivory, wind damage, and days with frost were measured or observed. The present study revealed that 82% of the variance in␣vascular species richness among sites could be explained by just two abiotic factors, daily maximum temperature and soil pH. Daily maximum temperature and pH affect species richness both directly and via their effects on other environmental variables. Some stress and disturbance factors were related to species richness in a monotonic way, others in an unimodal way. Monotonic relationships suggest that the harsher the environment is, the fewer species can survive in such habitats. In cases of unimodal relationships (ISH and IDH) species richness decreases at both ends of the gradients due to the harsh environment and/or the interaction of other environmental factors. Competition and disturbance seemed only to play a secondary role in the form of fine-tuning species richness in specific communities. Thus, we concluded that neither the ISH nor the IDH can be considered useful conceptual models for the alpine zone. Furthermore, we found that standing crop can be used as an easily measurable surrogate for causal factors determining species richness in the alpine zone, even though there is no direct causality.     

A new species of water mite <Emphasis Type="Italic">Atractides</Emphasis> (<Emphasis Type="Italic">Atractides</Emphasis>) <Emphasis Type="Italic">turcicus</Emphasis> sp. n. (Acari: Hydrachnidia: Hygrobatidae) from Turkey

In this study, the structural characteristics, unique features, various organ measurements of males and females of the water mite Atractides (Atractides) turcicus sp. n. from Turkey are described. In addition, the study compares their characteristics with related species.     

Cell cycle dependent alterations of chromatin structure in situ as revealed by the accessibility of the nuclear protein AF-2 to monoclonal antibodies.

We have recently described a novel nuclear antigen, AF-2, which is related to cell cycle dependent alterations of chromatin structure. We show by two parameter flow cytometry on a cell by cell basis that the antigen is accessible to specific monoclonal antibodies only in mitotic and postmitotic early G1-phase cells. The evaluation of nuclease susceptibility and AF-2 antigen accessibility reveals different subcompartments of the G1-phase of the cell cycle with distinct chromatin conformations. Digestion with DNase I seems to alter the chromatin structure according to concentration and this is reflected by an increase of the antigen accessibility. Chromatin in the more condensed early G1-phase is specifically digested by lower concentrations of the enzyme than chromatin in later stages of interphase. Chromatin from cells in the late-G1, S-, and G2-phases shows a higher relative resistance to DNase I and a reduced accessibility of the AF-2 antigen to monoclonal antibodies. Nuclease S1 has a similar effect on chromatin topology, as revealed by the reaction with anti-AF-2 antibodies, without digestion of detectable amounts of DNA. The antigen becomes available to the antibodies in almost all cells by digestion with high concentrations of DNase I or Nuclease S1.     

Proteins of the inner and outer centromere of mitotic chromosomes

We have used immunocytochemistry and molecular cloning methods to identify and characterize structural polypeptides of the centromere. These studies permit us to resolve two distinct regions: the inner and outer centromere. (i) Components of the outer centromere: autoantibodies from certain patients with rheumatic disease identify a family of three immunologically related polypeptides that we have designated CENP-A (17 kDa), CENP-B (80 kDa), and CENP-C (140 kDa). CENP-B has been cloned and sequenced. DNA sequence analysis indicates that this polypeptide possesses two large regions with extraordinary concentrations of acidic residues (region I: 61 residues with 79% glu + asp; region II: 31 residues with 87% glu + asp). Despite this concentration of negative charge, immunocytochemical experiments suggest that CENP-B may be a DNA binding protein. In these experiments, the levels of CENP-B are seen to vary reproducibly from chromosome to chromosome. The role of CENP-B in vivo is unknown. However, it is unlikely to bind directly to the spindle microtubules since it is found at an inactive centromere that apparently does not attach to the spindle. (ii) Components of the inner centromere: we have injected mice with the whole chromosome scaffold fraction to elicit production of monoclonal antibodies. One such antibody identifies two structurally related polypeptides (the INCENP antigens, 135 and 155 kDa) that are preferentially located between the sister chromatids at the centromere. The INCENP antigens undergo dramatic movements from the chromosomes to the central spindle during mitosis. They are ultimately sequestered in the midbody and discarded. Several lines of evidence suggest that the INCENP polypeptides may be involved in the regulation of sister chromatid separation at the metaphase-anaphase transition.