A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

Background  

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.     

Power and potential bias in field studies of natural selection

The advent of multiple regression analyses of natural selection has facilitated estimates of both the direct and indirect effects of selection on many traits in numerous organisms. However, low power in selection studies has possibly led to a bias in our assessment of the levels of selection shaping natural populations. Using calculations and simulations based on the statistical properties of selection coefficients, we find that power to detect total selection (the selection differential) depends on sample size and the strength of selection relative to the opportunity of selection. The power of detecting direct selection (selection gradients) is more complicated and depends on the relationship between the correlation of each trait and fitness and the pattern of correlation among traits. In a review of 298 previously published selection differentials, we find that most studies have had insufficient power to detect reported levels of selection acting on traits and that, in general, the power of detecting weak levels of selection is low given current study designs. We also find that potential publication bias could explain the trend that reported levels of direct selection tend to decrease as study sizes increase, suggesting that current views of the strength of selection may be inaccurate and biased upward. We suggest that studies should be designed so that selection is analyzed on at least several hundred individuals, the total opportunity of selection be considered along with the pattern of selection on individual traits, and nonsignificant results be actively reported combined with an estimate of power.     

Sculpting the proteome with AAA(+) proteases and disassembly machines

Machines of protein destruction-including energy-dependent proteases and disassembly chaperones of the AAA(+) ATPase family-function in all kingdoms of life to sculpt the cellular proteome, ensuring that unnecessary and dangerous proteins are eliminated and biological responses to environmental change are rapidly and properly regulated. Exciting progress has been made in understanding how AAA(+) machines recognize specific proteins as targets and then carry out ATP-dependent dismantling of the tertiary and/or quaternary structure of these molecules during the processes of protein degradation and the disassembly of macromolecular complexes.     

A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study

Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h²=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21–23 (LOD=2.29), and 6q24–26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.     

Analysis of cardiac signals using spatial filling index and time-frequency domain

Background  

Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming.     

Abnormal pulmonary slowly adapting receptors in canine acrylamide neuropathy

Slowly adapting lung stretch receptors (SARs) and their vagal afferents are considered to play an important role in the mediation of numerous respiratory reflexes. The understanding of such reflexes has been facilitated by altering the discharge properties of SARs or by preventing the conduction of SAR-generated impulses to the brain stem. In a number of naturally occurring diseases of the peripheral nervous system, the vagus nerve and vagal reflexes are damaged. We have studied the function of SARs in anesthetized dogs with acrylamide neuropathy, a distal axonopathy that has been used as a model of naturally occurring neuropathies. There was a marked increase in threshold and decrease in firing rate of SARs in dogs with moderate neuropathy. Abnormal SAR discharge patterns were observed, and there was a depletion of those units innervated by the fastest conducting vagal afferent fibers in treated animals. Acrylamide induced degeneration of myelinated fibers in bronchial branches of the vagus nerve. These abnormalities were partially reversed upon withdrawal of the neurotoxin. Acrylamide may be a useful agent in the study of vagally mediated respiratory reflexes. SAR function is likely to be abnormal in diseases of the peripheral nervous system.     

Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli

Strains of Escherichia coli carrying Tn10, a transposon consisting of two IS10 insertion sequences flanking a segment encoding for a tetracycline-resistance determinant, gain a competitive advantage in chemostat cultures. All Tn10-bearing strains that increase in frequency during competition have a new IS10 insertion that is found in the same location in the genome of those strains. We mapped, by a gradient of transmission, the position of the new IS10 insertion. We examined 11 isolates whose IS10 insertion was deleted by recombinational crossing- over, and in all cases the competitive fitness of the isolates was decreased. These results show that the IS10-generated insertion increases fitness in chemostat cultures. We named the insertion fit::IS10 and suggest that transposable elements may speed the rate of evolution by promoting nonhomologous recombination between preexisting variations within a genome and thereby generating adaptive variation.      

Molecular evolution of the ZFY and ZNF6 gene families

Members of the ZFY and ZNF6 gene families have been cloned from species representing different taxa and different modes of sex determination. Comparisons of these genes show the ZFY-like and ZNF6 sequences to be strongly conserved across marsupials, birds, and lepidosaurians. Sequence analyzed by neighbor-joining indicated that both gene families are monophyletic with a high bootstrap value. Pairing of sequences from males and females of nonmammalian species showed there to be no significant difference between male and female sequences from a single species, consistent with autosomal locations. The molecular distances between murine Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have undergone a period of rapid evolutionary change not seen in human ZFY.      

Monitoring the atmosphere in an anaerobic chamber

The Couloximeter, a fuel cell designed to measure trace amounts of oxygen, was used to monitor the atmosphere in an anaerobic chamber. The device, easy to operate and to maintain, allowed both major and minor fluctuations in oxygen concentration to be measured. Using a hose attached to the outlet within the box, defective (ruptured) gloves were consistently distinguishable from intact gloves.