Human Uterine Wall Tension Trajectories and the Onset of Parturition

Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000–2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.     

Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: a pilot study

Introduction  

Rheumatoid arthritis (RA) is a multi-organ inflammatory disorder associated with high cardiovascular morbidity and mortality. We sought to assess cardiac involvement using a comprehensive cardiac magnetic resonance imaging (cMRI) approach and to determine its association with disease characteristics in RA patients without symptomatic cardiac disease.     

Hypothalamic-Specific Manipulation of Fto,the Ortholog of the Human Obesity Gene FTO,Affects Food Intake in Rats

Sequence variants in the first intron of FTO are strongly associated with human obesity and human carriers of the risk alleles show evidence for increased appetite and food intake. Mice globally lacking Fto display a complex phenotype characterised by both increased energy expenditure and increased food intake. The site of action of FTO on energy balance is unclear. Fasting reduces levels of Fto mRNA in the arcuate nucleus (ARC) of the hypothalamus, a site where Fto expression is particularly high. In this study, we have extended this nutritional link by demonstrating that consumption of a high fat diet (45%) results in a 2.5 fold increase in Arc Fto expression. We have further explored the role of hypothalamic Fto in the control of food intake by using stereotactic injections coupled with AAV technology to bi-directionally modulate Fto expression. An over expression of Fto protein by 2.5-fold in the ARC results in a 14% decrease in average daily food intake in the first week. In contrast, knocking down Arc Fto expression by 40% increases food intake by 16%. mRNA levels of Agrp, Pomc and Npy, ARC-expressed genes classically associated with the control of food intake, were not affected by the manipulation of Fto expression. However, over expression of Fto resulted in a 4-fold increase in the mRNA levels of Stat3, a signalling molecule critical for leptin receptor signalling, suggesting a possible candidate for the mediation of Fto''s actions. These data provide further support for the notion that FTO itself can influence key components of energy balance, and is therefore a strong candidate for the mediation of the robust association between FTO intronic variants and adiposity. Importantly, this provide the first indication that selective alteration of FTO levels in the hypothalamus can influence food intake, a finding consistent with the reported effects of FTO alleles on appetite and food intake in man.     

Reduced rates of primary joint replacement for osteoarthritis in Italian and Greek migrants to Australia: the Melbourne Collaborative Cohort Study

Introduction  

Racial and ethnic disparities in rates of total joint replacement have been described, but little work has been done in well-established migrant groups. The aim of this study was to compare the rates of primary joint replacement for osteoarthritis for Italian and Greek migrants to Australia and Australian-born individuals.     

TorsinA protein degradation and autophagy in DYT1 dystonia

Early-onset generalized dystonia (DYT1) is a debilitating neurological disorder characterized by involuntary movements and sustained muscle spasms. DYT1 dystonia has been associated with two mutations in torsinA that result in the deletion of a single glutamate residue (torsinA DeltaE) and six amino-acid residues (torsinA Delta323-8). We recently revealed that torsinA, a peripheral membrane protein, which resides predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), is a long-lived protein whose turnover is mediated by basal autophagy. Dystonia-associated torsinA DeltaE and torsinA Delta323-8 mutant proteins show enhanced retention in the NE and accelerated degradation by both the proteasome and autophagy. Our results raise the possibility that the monomeric form of torsinA mutant proteins is cleared by proteasome-mediated ER-associated degradation (ERAD), whereas the oligomeric and aggregated forms of torsinA mutant proteins are cleared by ER stress-induced autophagy. Our findings provide new insights into the pathogenic mechanism of torsinA DeltaE and torsinA Delta323-8 mutations in dystonia and emphasize the need for a mechanistic understanding of the role of autophagy in protein quality control in the ER and NE compartments.     

Nonphotochemical quenching of chlorophyll fluorescence in Chlamydomonas reinhardtii

Unlike plants, Chlamydomonas reinhardtii shows a restricted ability to develop nonphotochemical quenching upon illumination. Most of this limited quenching is due to state transitions instead of DeltapH-driven high-energy state quenching, qE. The latter could only be observed when the ability of the cells to perform photosynthesis was impaired, either by lowering temperature to approximately 0 degrees C or in mutants lacking RubisCO activity. Two main features were identified that account for the low level of qE in Chlamydomonas. On one hand, the electrochemical proton gradient generated upon illumination is apparently not sufficient to promote fluorescence quenching. On the other hand, the capacity to transduce the presence of a DeltapH into a quenching response is also intrinsically decreased in this alga, when compared to plants. The possible mechanism leading to these differences is discussed.