Rapid evolution towards equal sex ratios in a system with heterogamety

The equal sex ratios found in many species with heterogametic sex determination may be a consequence of selection for equality or the result of the Mendelian segregation of the two sex chromosomes. A lack of genetic variation in sex ratio in species with heterogamety has been the major obstacle in distinguishing between these two hypotheses. We overcome this obstacle by generating hybrids between two species of Drosophila. The resulting hybrid lines had biased sex ratios, allowing us to observe the evolution of sex ratio in replicate populations. Sex ratio converged towards 1:1 after 16 generations of natural selection. These changes in sex ratio were not due to differences in viability between the sexes and the loci underlying the variation in sex ratio were not sex-linked. Equal sex ratios may therefore be the result of natural selection as Fisher predicted.

Temperature-dependent sex ratio in a bird

To our knowledge, there is, so far, no evidence that incubation temperature can affect sex ratios in birds, although this is common in reptiles. Here, we show that incubation temperature does affect sex ratios in megapodes, which are exceptional among birds because they use environmental heat sources for incubation. In the Australian brush-turkey Alectura lathami, a mound-building megapode, more males hatch at low incubation temperatures and more females hatch at high temperatures, whereas the proportion is 1 : 1 at the average temperature found in natural mounds. Chicks from lower temperatures weigh less, which probably affects offspring survival, but are not smaller. Megapodes possess heteromorphic sex chromosomes like other birds, which eliminates temperature-dependent sex determination, as described for reptiles, as the mechanism behind the skewed sex ratios at high and low temperatures. Instead, our data suggest a sex-biased temperature-sensitive embryo mortality because mortality was greater at the lower and higher temperatures, and minimal at the middle temperature where the sex ratio was 1 : 1.

Using MF-PCR to diagnose multiple defects from single cells: implications for PGD

Single cell genetic analysis is generally performed using PCR and FISH. Until recently, FISH has been the method of choice. FISH however is expensive, has significant misdiagnosis rates, can result in interpretation difficulties and is labour intensive making it unsuitable for high throughput processing. Recently fluorescent PCR reliability has increased to levels at or surpassing FISH whilst maintaining low cost. However, PCR accuracy has been a concern due to allelic dropout. Multiplex PCR can now increase accuracy by using multiple markers for each chromosome to firstly provide diagnosis if markers fail and,or secondly confirm diagnosis. We compare a variety of diagnostic methods and demonstrate for the first time a multiplex PCR system providing simultaneous diagnosis and confirmation of the major aneuploidy chromosomes (21, 18, 13) and sex as well as DNA fingerprint in single cells. We also discuss the implications of using PCR for aneuploidy screening in preimplantation genetic diagnosis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Allelic Variation Investigation of the Estrogen Receptor Within an Australian Multiple Sclerosis Population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

Articulatory dysfunction in multiple sclerosis: An electropalatographic study

Dysfunction of the articulatory subsystem (i.c.. the lips, tongue, and jaw) has bccn identified as a major contributor to the reduction in speech intelligibility experienced by a high proportion of people with multiple sclerosis (MS). In particular. consonant imprecision has been reported to be the articulatory deficit that contributes most to variations in overall intelligibility of MS speakers. Electropalatography(EPG) IS an instrurncntal technique that visually documents the location and timing of tongue-topalatc contacts during speech. Although such a technique would be valuablc in objectively assessing the articulatory disturbances exhibited by individuals with dysarthria ia motor speech disorder) associated with MS, to-date no such study ha< been reported. The aim of the present study was to use EPG to assess tongue-to-palate contact patterns and articulatory timing in patients with dysarthria associated with MS. A dysarthric participant with a diagnosis of definite MS was fitted with an acrylic EPG palate (Reading EPG.?) and asked to read aloud a list of single syllable words which contained lingual consonants in the word-initial position and in consonant clusters. Each mord was repeated five times. The EPG palate was specifically moulded to tit the participant's hard palate and contained 62 electrodes that detected the tongue contacts. A non-neurologically impaired participant matched for age and sex servcd as a control. The results of the study revealed that the tongue-to-palate contacts produced by the participant with MS varied from those produced by the control in a number of ways in regard to spatial configurations and timing characteristics exhibited. The rcsults arc discussed in relation to the neuropathophysiological effects of MS on speech production. The potcntial use of EPG in programs for treating speech disorders associated with MS will be highlightcd.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes

Despite the identification of SRY as the testis-determining gene in mammals, the genetic interactions controlling the earliest steps of male sex determination remain poorly understood. In particular, the molecular lesions underlying a high proportion of human XY gonadal dysgenesis, XX maleness and XX true hermaphroditism remain undiscovered. A number of screens have identified candidate genes whose expression is modulated during testis or ovary differentiation in mice, but these screens have used whole gonads, consisting of multiple cell types, or stages of gonadal development well beyond the time of sex determination. We describe here a novel reporter mouse line that expresses enhanced green fluorescent protein under the control of an Sf1 promoter fragment, marking Sertoli and granulosa cell precursors during the critical period of sex determination. These cells were purified from gonads of male and female transgenic embryos at 10.5 dpc (shortly after Sry transcription is activated) and 11.5 dpc (when Sox9 transcription begins), and their transcriptomes analysed using Affymetrix genome arrays. We identified 266 genes, including Dhh, Fgf9 and Ptgds, that were upregulated and 50 genes that were downregulated in 11.5 dpc male somatic gonad cells only, and 242 genes, including Fst, that were upregulated in 11.5 dpc female somatic gonad cells only. The majority of these genes are novel genes that lack identifiable homology, and several human orthologues were found to map to chromosomal loci implicated in disorders of sexual development. These genes represent an important resource with which to piece together the earliest steps of sex determination and gonad development, and provide new candidates for mutation searching in human sexual dysgenesis syndromes.

The origin of the pelagobenthic metazoan life cycle: what's sex got to do with it?

The biphasic (pelagobenthic) life cycle is found throughout the animal kingdom, and includes gametogenesis, embryogenesis, and metamorphosis. From a tangled web of hypotheses on the origin and evolution of the metazoan pelagobenthic life cycle, current opinion appears to favor a simple, larval-like holopelagic ancestor that independently settled multiple times to incorporate a benthic phase into the life cycle. This hypothesis derives originally from Haeckel's (1874) Gastraea theory of ontogeny recapitulating phylogeny, in which the gastrula is viewed as the recapitulation of a gastracan ancestor that evolved via selection on a simple, planktonic hollow ball of cells to develop the capacity to feed. Here, we propose an equally plausible hypothesis that the origin of the metazoan pelagobenthic life cycle was a direct consequence of sexual reproduction in a likely holobenthic ancestor. In doing so, we take into account new insights from poriferan development and from molecular phylogenies. In this scenario, the gastrula does not represent a recapitulation, but simply an embryological stage that is an outcome of sexual reproduction. The embryo can itself be considered as the precursor to a biphasic lifestyle, with the embryo representing one phase and the adult another phase. This hypothesis is more parsimonious because it precludes the need for multiple, independent origins of the benthic form. It is then reasonable to consider that multilayered, ciliated embryos ultimately released into the water column are subject to natural selection for dispersal/longevity/feeding that sets them on the evolutionary trajectory towards the crown metazoan planktonic larvae. These new insights from poriferan development thus clearly support the intercalation hypothesis of bilaterian larval evolution, which we now believe should be extended to discussions of the origin of biphasy in the metazoan last common ancestor.

Effect of multiple transverse modes in self-mixing sensors based on vertical-cavity surface-emitting lasers

We investigate the effect of coexisting transverse modes on the operation of self-mixing sensors based on vertical-cavity surface-emitting lasers (VCSELs). The effect of multiple transverse modes on the measurement of displacement and distance were examined by simulation and in laboratory experiment. The simulation model shows that the periodic change in the shape and magnitude of the self-mixing signal with modulation current can be properly explained by the different frequency-modulation coefficients of the respective transverse modes in VCSELs. The simulation results are in excellent agreement with measurements performed on single-mode and multimode VCSELs and on self-mixing sensors based on these VCSELs.

The origin of a Robertsonian chromosomal translocation in house mice inferred from linked microsatellite markers

The Western European house mouse, Mus domesticus, includes many distinct Robertsonian (Rb) chromosomal races. Two competing hypotheses may explain the distribution of Rb translocations found in different populations: they may have arisen independently multiple times or they may have arisen once and been spread through long distance dispersal. We investigated the origin of the Rb 5.15 translocation using 6 microsatellite loci linked to the centromeres of chromosomes 5 and 15 in 84 individuals from 3 Rb populations and 4 neighboring standard-karyotype populations. Microsatellite variation on the 5.15 metacentric chromosomes was significantly reduced relative to the amount of variation found on acrocentric chromosomes 5 and 15, suggesting that linked microsatellite loci can track specific mutational events. Phylogenetic analyses resulted in trees which are consistent with multiple origins of the 5.15 metacentric found in the three Rb populations. These results suggest that cytologically indistinguishable mutations have arisen independently in natural populations of house mice.

Multiple Sclerosis with Idiopathic Dilated Cardiomyopathy: A Case Report

Multiple sclerosis and idiopathic dilated cardiomyopathy are two conditions in which an autoimmune process is implicated in the pathogenesis. There is evidence to support clustering of autoimmune diseases in patients with multiple sclerosis and their families. To our knowledge, this is the first report of idiopathic dilated cardiomyopathy occurring in a patient with multiple sclerosis.

Existence of Multiple Solutions for Second Order Boundary Value Problems

We give conditions on f involving pairs of lower and upper solutions which lead to the existence of at least three solutions of the two point boundary value problem y" + f(x, y, y') = 0, x epsilon [0, 1], y(0) = 0 = y(1). In the special case f(x, y, y') = f(y) greater than or equal to 0 we give growth conditions on f and apply our general result to show the existence of three positive solutions. We give an example showing this latter result is sharp. Our results extend those of Avery and of Lakshmikantham et al.