Disentangling Genetic and Prenatal Maternal Effects on Offspring Size and Survival

This is the author accepted manuscript. The final version is available from University of Chicago Press via the DOI in this record.Organizational processes during prenatal development can have long-term effects on an individual's phenotype. Because these early developmental stages are sensitive to environmental influences, mothers are in a unique position to alter their offspring's phenotype by differentially allocating resources to their developing young. However, such prenatal maternal effects are difficult to disentangle from other forms of parental care, additive genetic effects, and/or other forms of maternal inheritance, hampering our understanding of their evolutionary consequences. Here we used divergent selection lines for high and low prenatal maternal investment and their reciprocal line crosses in a precocial bird-the Japanese quail (Coturnix japonica)-to quantify the relative importance of genes and prenatal maternal effects in shaping offspring phenotype. Maternal but not paternal origin strongly affected offspring body size and survival throughout development. Although the effects of maternal egg investment faded over time, they were large at key life stages. Additionally, there was evidence for other forms of maternal inheritance affecting offspring phenotype at later stages of development. Our study is among the first to successfully disentangle prenatal maternal effects from all other sources of confounding variation and highlights the important role of prenatal maternal provisioning in shaping offspring traits closely linked to fitness.The study was financially supported by the Swiss National Science Foundation (PP00P3_128386 and PP00P3_157455 to B.T.)

Postoperative sepsis in infants below 6 months of age

Background: Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. Methods: We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. Results: The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). Conclusions: Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigation

A search for features in early-type galaxies

We have conducted a search for dust lanes, incipient stellar disks, bars, shells, and other deviations from elliptical symmetry in a sample of 159 early-type galaxies. The data are from the CCD surface-photometry survey of Djorgovski (1985a), for which the selection effects are well understood. The image-processing technique used is division by a purely elliptical model image, constructed from the surfacephotometry profiles for a given object (best-fit surface brightness, ellipticity, and position angle as functions of semimajor axis). Our sample contains 116 elliptical galaxies, 33 SO galaxies, and ten intermediate types. Some galaxies that might better be classified as “dusty ellipticals“ (in that they contain no obvious stellar disk) are included among the SOs. Forty-two of the ellipticals (36%) either definitely or very likely contain dust, either in patches or in well-defined lanes or rings. Five of the E/SO galaxies (50%) also show possible or definite dust, as do 15 (47%) of the SOs. Three of the elliptical galaxies definitely contain stellar disks, with several more possible candidates. Thus, approximately 50% of the elliptical galaxies show “features“ of some kind. The detection of features is dependent on the signal-to-noise ratio of the data, so these numbers represent lower limits. The presence of dust in the galaxies classified as ellipticals does not seem to depend on any intrinsic characteristic of the galaxy. The dusty ellipticals do seem to prefer low-density environments. The “elliptical“ galaxies with disks tend to have higher ellipticities and larger two-wave Fourier residuals, an effect also described by Carter ( 1987). These galaxies may be preferentially found in higher-density environments, and may be lower-luminosity systems, but these statements are based on very small-number statistics (ten galaxies out of a total of 116), and no strong conclusions may be drawn. However, our results clearly further blur the distinction between ellipticals and SOs

A trade-off between reproductive investment and maternal cerebellum size in a precocial bird

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this record.Natural selection favours increased investment in reproduction, yet considerable variation in parental investment is observed in natural populations. Life-history theory predicts that this variation is maintained by a trade-off between the benefits of increased reproductive investment and its associated costs for the parents. The nature of these costs of reproduction, however, remains poorly understood. The brain is an energetically highly expensive organ and increased reproductive investment may, therefore, negatively affect brain maintenance. Using artificial selection lines for high and low prenatal maternal investment in a precocial bird, the Japanese quail (Coturnix japonica), we provide experimental evidence for this hypothesis by showing that increased prenatal provisioning negatively affects the size of a particular brain region of the mother, the cerebellum. Our finding suggests that cognitive demands may constrain the evolution of parental investment, and vice versa, contributing to the maintenance of variation in reproductive behaviour in animal populations.This work was supported by the Swiss National Science Foundation (PP00P3_128386, PP00P3_157455 to B.T.) and the Georges und Antoine Claraz-Schenkung (to C.E.)

Present Molecular Limitations of ON-Bipolar Cell Targeted Gene Therapy

Recent studies have demonstrated the safety and efficacy of ocular gene therapy based on adeno-associated viral vectors (AAVs). Accordingly, a surge in promising new gene therapies is entering clinical trials, including the first optogenetic therapy for vision restoration. To date, optogenetic therapies for vision restoration target either the retinal ganglion cells (GCs) or presynaptic ON-bipolar cells (OBCs). Initiating light responses at the level of the OBCs has significant advantages over optogenetic activation of GCs. For example, important neural circuitries in the inner retina, which shape the receptive fields of GCs, remain intact when activating the OBCs. Current drawbacks of AAV-mediated gene therapies targeting OBCs include (1) a low transduction efficiency, (2) off-target expression in unwanted cell populations, and (3) a poor performance in human tissue compared to the murine retina. Here, we examined side-by-side the performance of three state-of-the art AAV capsid variants, AAV7m8, AAVBP2, and AAV7m8(Y444F) in combination with the 4xGRM6-SV40 promoter construct in the healthy and degenerated mouse retina and in human post-mortem retinal explants. We find that (1) the 4xGRM6-SV40 promoter is not OBC specific, (2) that all AAV variants possess broad cellular transduction patterns, with differences between the transduction patterns of capsid variants AAVBP2 and AAV7m8 and, most importantly, (3) that all vectors target OBCs in healthy tissue but not in the degenerated rd1 mouse model, potentially limiting the possibilities for an OBC-targeted optogenetic therapy for vision restoration in the blind

Cyst-Wall-Protein-1 is fundamental for Golgi-like organelle neogenesis and cyst-wall biosynthesis in Giardia lamblia

The genome of the protozoan parasite Giardia lamblia is organized in two diploid nuclei, which has so far precluded complete analysis of gene function. Here we use a previously developed Cre/loxP-based knock-out and selection marker salvage strategy in the human-derived isolate WB-C6 to eliminate all four copies of the Cyst-Wall-Protein-1 locus (CWP1). Because these loci are silenced in proliferating trophozoites and highly expressed only in encysting cells, CWP1 ablation allows functional characterization of a conditional phenotype in parasites induced to encyst. We show that encysting Δcwp1 cells are unable to establish the stage-regulated trafficking machinery with Golgi-like encystation-specific vesicles required for cyst-wall formation but show morphological hallmarks of cyst development and karyokinesis. This ‘pseudocyst’ phenotype is rescued by transfection of Δcwp1 cells with an episomally maintained CWP1 expression vector. Genome editing in genera Giardia and Trypanosoma are the only reported examples addressing questions on pathogen transmission within the Excavata supergroup

Multi-method-modeling of interacting galaxies. I. A unique scenario for NGC 4449?

(abridged) We combined several N-body methods in order to investigate the interaction scenario between NGC 4449 and DDO 125, a close companion in projected space. In a first step fast restricted N-body models are used to confine a region in parameter space reproducing the main observational features. In a second step a genetic algorithm is applied for a uniqueness test of our preferred parameter set. We show that our genetic algorithm reliably recovers orbital parameters, provided that the data are sufficiently accurate, i.e. all the key features are included. In the third step the results of the restricted N-body models are compared with self-consistent N-body simulations. In the case of NGC 4449, the applicability of the simple restricted N-body calculations is demonstrated. Additionally, it is shown that the HI gas can be modeled here by a purely stellar dynamical approach. In a series of simulations, we demonstrate that the observed features of the extended HI disc can be explained by a gravitational interaction between NGC 4449 and DDO 125. According to these calculations the closest approach between both galaxies happened $\sim 4-6 \cdot 10^8$ yr ago at a minimum distance of $\sim 25$ kpc on a parabolic or slightly elliptic orbit. In the case of an encounter scenario, the dynamical mass of DDO 125 should not be smaller than 10% of NGC 4449's mass. Before the encounter, the observed HI gas was arranged in a disc with a radius of 35-40 kpc around the center of NGC 4449. It had the same orientation as the central ellipsoidal HI structure. The origin of this disc is still unclear, but it might have been caused by a previous interaction.Comment: 19 pages with 19 figures, accepted for publication in Astron. & Astrophys., a full PostScript version is available at http://www.astrophysik.uni-kiel.de/pershome/theis/pub.htm

Latex on Glass: an Appropriate Model for Cartilage-Lubrication Studies?

Latex versus glass has frequently been used as a model system for the investigation of natural lubrication mechanisms, despite its significant differences from articular cartilage pairings. The differences in surface chemistry account for its different behavior in terms of protein adsorption and lubrication. While cartilage is well known for its protein resistance, most proteins present in synovial fluid can non-specifically adsorb onto latex or glass. We have investigated latex-versus-glass lubrication by means of pin-on-disk tribometry in the presence of synovial-fluid proteins and glycoproteins, focusing on the influence of the glass-cleaning procedure on friction. In order to simulate the effects of possible contamination of glass in previous studies, both hydrophilic and hydrophobic glass substrates were tested. Albumin was shown to impair lubrication (in comparison to PBS) when latex was slid against both types of glass surface, whereas bovine synovial fluid (BSF) and alpha-1-acid glycoprotein (AGP) impaired the lubrication of latex versus hydrophilic glass and improved the lubrication of latex versus hydrophobic glass. Protein adsorption on the surfaces was monitored by means of fluorescence imaging and optical waveguide lightmode spectroscopy (OWLS), which revealed a faster and greater amount of adsorption of AGP on hydrophobic surfaces than on hydrophilic ones. The influence of surface chemistry on the friction behavior of BSF and on the adsorption of AGP suggests that it plays a role in determining the relative amounts of adsorbed synovial fluid proteins. When BSF is used as a lubricant in the latex-versus-hydrophobic-glass system, more of the AGP, relative to albumin, appears to adsorb on both surfaces, counteracting the negative effect of albumin on friction. It therefore seems that latex on glass, while displaying nominal similarities to cartilage on cartilage under certain conditions, is not a useful model system. Moreover, surface contamination of the glass can play a major role in determining the result