Is reproduction of the Australian house mouse (<Emphasis Type="Italic">Mus domesticus</Emphasis>) constrained by food? A large-scale field experiment

Food quantity and especially food quality are thought to be key factors driving reproductive changes in the house mouse, Mus domesticus, leading to outbreaks of house mouse populations in the Australian grain-growing region. Characteristic changes during an incipient mouse plague are an early start of breeding, a high proportion of females breeding at a young age and a prolonged breeding season. We conducted a large-scale food manipulation during an incipient mouse plague, which started with early breeding and relatively high spring numbers of mice. We measured background food availability in four farms throughout the study and conducted a food manipulation experiment from November to March in two of them. After harvest in December 100-200 kg/ha spilled grain remained in the stubble. This was depleted by March. In two treatment farms we added high-protein food pellets on a weekly basis between November and March and two farms served as controls. We measured changes in mouse numbers by capture-mark-recapture trappings and changes in reproduction by scoring embryos and recent placental scars at necropsy. Mouse numbers did not differ between treatments and controls. There were no differences in the litter size or the proportion of females breeding between treatments and controls. We observed the normal pattern of high litter size in spring and decreasing litter size towards the end of summer in treatments and controls. In all farms reproduction stopped in March. Mouse numbers were high but not at plague densities. Contrary to our prediction we did not observe food constraint affecting the reproduction of female mice. Our field experiment seems to rule out food quality as the driving factor for improved reproduction and formation of an outbreak of mice. We suggest that physiological mechanisms in mice might not enable them to take advantage of food with a high protein content in arid summers in southeastern Australian grain fields because of the lack of free-standing water.     

Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta-analyses adjusted for differences in study design and quality

Background

To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted.

Methods

Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis.

Results

In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I ² = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I ² = 0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28–30 weeks is least effective.

Conclusion

There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.     

Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

This study examines some of the cardiovascular and respiratory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in anaesthetised dogs. Intravenous injection of PACAP 27 caused an increase in arterial blood pressure and an increase in heart rate. The blood pressure response was significantly reduced by adrenoceptor blockade suggesting a mechanism of action mediated in part via catecholamines. The heart rate increase was unaltered by adrenoceptor blockade suggesting a direct effect of PACAP 27. PACAP 27 also caused potentiation of cardiac slowing caused by stimulation of the vagus nerve. In addition, PACAP 27 powerfully stimulated breathing. This was probably evoked by stimulation of arterial chemoreceptors, because bilateral section of the carotid sinus nerves abolished this effect. PACAP 27 had no effect on the ability of the cardiac sympathetic nerve to increase heart rate, nor on the interaction between the sympathetic and parasympathetic systems in the heart.     

Infection and Inflammation in Schizophrenia and Bipolar Disorder: A Genome Wide Study for Interactions with Genetic Variation

Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.     

SPIRE—a software tool for bicontinuous phase recognition: application for plastid cubic membranes

Bicontinuous membranes in cell organelles epitomize nature’s ability to create complex functional nanostructures. Like their synthetic counterparts, these membranes are characterized by continuous membrane sheets draped onto topologically complex saddle-shaped surfaces with a periodic network-like structure. Their structure sizes, (around 50–500 nm), and fluid nature make transmission electron microscopy (TEM) the analysis method of choice to decipher their nanostructural features. Here we present a tool, Surface Projection Image Recognition Environment (SPIRE), to identify bicontinuous structures from TEM sections through interactive identification by comparison to mathematical “nodal surface” models. The prolamellar body (PLB) of plant etioplasts is a bicontinuous membrane structure with a key physiological role in chloroplast biogenesis. However, the determination of its spatial structural features has been held back by the lack of tools enabling the identification and quantitative analysis of symmetric membrane conformations. Using our SPIRE tool, we achieved a robust identification of the bicontinuous diamond surface as the dominant PLB geometry in angiosperm etioplasts in contrast to earlier long-standing assertions in the literature. Our data also provide insights into membrane storage capacities of PLBs with different volume proportions and hint at the limited role of a plastid ribosome localization directly inside the PLB grid for its proper functioning. This represents an important step in understanding their as yet elusive structure–function relationship.

The SPIRE tool facilitates recognition of bicontinuous phases on transmission electron micrographs, which enables in-depth spatial prolamellar body structure analysis from 2D micrographs.