Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome

Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas-/- animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas-/- and wild-type mice. Aaas-/- mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease.     

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001).     

Assessment of energy requirement for the retinal arterial network in normal and hypertensive subjects

The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement.     

Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip

To prevent and treat immune-mediated platelet disorders (e.g. neonatal allo-immune thrombocytopenia and platelet transfusion refractoriness) the causative idiotypic platelet-reactive antibodies have to be detected with high sensitivity and specificity. The "Monoclonal Antibody Immobilization Platelet Assay" (MAIPA) is the diagnostic gold standard for immunotyping sera with respect to alloantibodies against human platelet antigens (HPA). However, it is labor-intensive and time-consuming. In this work, an automated protein chip assay (enzyme-linked sandwich immunoassay) based on interdigitated gold microelectrodes in combination with an electrical read-out system was developed and optimized. For this purpose, specific capture antibodies were immobilized on the gold electrodes. The binding of the target is detected via an enzyme-labeled detection antibody by a redox-recycling process that corresponds to the amount of bound target molecule. With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance.     

Hospital Recorded Morbidity and Breast Cancer Incidence: A Nationwide Population-Based Case-Control Study

Introduction

Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth.

Methods

Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods.

Results

The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment.

Conclusions

There was no substantial association between morbidity measured with the CCI and breast cancer risk.     

Pollinator‐prey conflict in carnivorous plants

Most carnivorous plants utilize insects in two ways: the flowers attract insects as pollen vectors for sexual reproduction, and the leaves trap insects for nutrients. Feeding on insects has been explained as an adaptation to nutrient‐poor soil, and carnivorous plants have been shown to benefit from insect capture through increased growth, earlier flowering and increased seed production. Most carnivorous plant species seem to benefit from insect pollination, although many species autonomously self‐pollinate and some propagate vegetatively. However, assuming that outcross pollen is advantageous and is a more important determinant of reproductive success than the nutrients gained from prey, there should be a selective pressure on carnivorous plants not to feed on their potential pollen vectors. Therefore, it has been suggested that carnivorous plants are subject to a conflict, often called the pollinator‐prey conflict (PPC). The conflict results from a trade‐off of the benefits from feeding on potentially pollinating insects versus the need to use them as pollen vectors for sexual reproduction. In this review we analyze the conditions under which a PPC may occur, review the evidence for the existence of PPCs in carnivorous plants, and explore the mechanisms that may be in place to prevent or alleviate a PPC. With respect to the latter, we discuss how plant signals such as olfactory and visual cues may play a role in separating the functions of pollinator attraction and prey capture.