Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution

Mammary gland development is dependent on macrophages, as demonstrated by their requirement during the expansion phases of puberty and pregnancy. Equally dramatic tissue restructuring occurs following lactation, when the gland regresses to a state that histologically resembles pre-pregnancy through massive programmed epithelial cell death and stromal repopulation. Postpartum involution is characterized by wound healing-like events, including an influx of macrophages with M2 characteristics. Macrophage levels peak after the initial wave of epithelial cell death, suggesting that initiation and execution of cell death are macrophage independent. To address the role of macrophages during weaning-induced mammary gland involution, conditional systemic deletion of macrophages expressing colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning in the Mafia mouse model. Depletion of CSF1R(+) macrophages resulted in delayed mammary involution as evidenced by loss of lysosomal-mediated and apoptotic epithelial cell death, lack of alveolar regression and absence of adipocyte repopulation 7 days post-weaning. Failure to execute involution occurred in the presence of milk stasis and STAT3 activation, indicating that neither is sufficient to initiate involution in the absence of CSF1R(+) macrophages. Injection of wild-type bone marrow-derived macrophages (BMDMs) or M2-differentiated macrophages into macrophage-depleted mammary glands was sufficient to rescue involution, including apoptosis, alveolar regression and adipocyte repopulation. BMDMs exposed to the postpartum mammary involution environment upregulated the M2 markers arginase 1 and mannose receptor. These data demonstrate the necessity of macrophages, and implicate M2-polarized macrophages, for epithelial cell death during normal postpartum mammary gland involution.     

DBA/2J Genetic Background Exacerbates Spontaneous Lethal Seizures but Lessens Amyloid Deposition in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APP^swe and PSEN1^de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1^de9 has not been tested. Our study shows that DBA/2J.APP^swePSEN1^de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APP^swePSEN1^de9 mice—70% of DBA/2J.APP^swePSEN1^de9 mice die between 2-3 months of age. Of the DBA/2J.APP^swePSEN1^de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APP^swePSEN1^de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity.     

Production and Characterization of Monoclonal Antibodies to Wall-Localized Peroxidases from Corn Seedlings

A library of 22 hybridomas, which make antibodies to soluble wall antigens from the coleoptiles and primary leaves of etiolated corn (Zea mays L.) seedlings, was raised and cloned three times by limit dilution to assure monoclonal growth and stability. Two of these hybridomas made immunoglobulin G antibodies, designated mWP3 and mWP19, which both effectively immunoprecipitated peroxidase activity from crude and partially purified preparations of wall peroxidases. Direct peroxidase-binding assays revealed that both antibodies bound enzymes with peroxidase activity. As judged by immunoblot analyses, mWP3 recognized a M_r 98,000 wall peroxidase with an isoelectric point near 4.2, and mWP19 recognized a M_r 58,000 wall peroxidase. Immunogold localization studies showed both peroxidases are predominately in cell walls.     

The evolved psychological mechanisms of fertility motivation: hunting for causation in a sea of correlation

Cultural, ecological, familial and physiological factors consistently influence fertility behaviours, however, the proximate psychological mechanisms underlying fertility decisions in humans are poorly understood. Understanding the psychological mechanisms underlying human fertility may illuminate the final processes by which some of these known predictors have their influence. To date, research into the psychological mechanisms underlying fertility has been fragmented. Aspects of reproductive psychology have been examined by researchers in a range of fields, but the findings have not been systematically integrated in one review. We provide such a review, examining current theories and research on psychological mechanisms of fertility. We examine the methods and populations used in the research, as well as the disciplines and theoretical perspectives from which the work has come. Much of the work that has been done to date is methodologically limited to examining correlations between ecological, social and economic factors and fertility. We propose, and support with examples, the use of experimental methods to differentiate causal factors from correlates. We also discuss weaknesses in the experimental research, including limited work with non-WEIRD (western, educated, industrialized, rich and democratic) populations.     

Plasminogen activator inhibitor-1 is induced in migrating endothelial cells.

It has been proposed that a finely tuned protease-anti-protease equilibrium must be maintained during processes of cell migration in order to limit extracellular proteolysis to the close proximity of the cell surface, and thereby to prevent excessive extracellular matrix degradation. We have previously shown that urokinase-type plasminogen activator (u-PA) activity is induced in microvascular endothelial cells migrating from the edges of a wounded monolayer in vitro (Pepper et al., J. Cell Biol., 105:2535-2541, 1987). By Northern analysis, we now demonstrate that plasminogen activator inhibitor 1 (PAI-1) mRNA is increased in multiple-wounded monolayers of bovine microvascular (BME) or aortic (BAE) endothelial cells, with a maximal 7- and 9-fold increase 4 h after wounding, respectively. By in situ hybridization, we demonstrate that the increase in PAI-1 mRNA is localized to cells at the edge of a wounded BME or BAE cell monolayer. The increase in PAI-1 mRNA observed in BME cells is independent of cell division and is inhibited by antibodies to basic fibroblast growth factor (bFGF), suggesting that PAI-1 induction in migrating cells is mediated by the autocrine activity of bFGF. Taken together with our previous observations on the induction of u-PA, these results support the hypothesis that the proteolytic balance in the pericellular environment of migrating cells is regulated through the concomitant production of proteases and protease inhibitors.     

The spatial and temporal distribution of predatory and phytophagous mites in field-grown strawberry in the UK

Extensive sampling of strawberry plants in everbearing and June-bearing strawberry plantations and on potted plants showed that different species of mites were spatially separated. Of the two phytophagous species recorded, Tetranychus urticae was most abundant on old leaves and Phytonemus pallidus on folded leaves and flower/fruit clusters. Predatory phytoseiid mites were found on all plant parts but different species were spatially separated; Neoseiulus cucumeris and N. aurescens were found mostly on folded leaves and clusters, and N. californicus and Phytoseiulus persimilis on old and medium aged leaves. No Typhlodromus pyri were found in the field plantations. These patterns of distribution did not change over sampling dates in summer and early autumn. An understanding of this within-plant zonation of mite species is important when studying predator–prey interactions and when designing sampling strategies for strawberry. A programme to sample the entire mite system on strawberry should be stratified to include all the above mentioned parts of the plant. Different sampling protocols, as appropriate, are required for sampling different pest species and their associated predators.     

Multilocus phylogeography reveals nested endemism in a gecko across the monsoonal tropics of Australia

Multilocus phylogeography can uncover taxonomically unrecognized lineage diversity across complex biomes. The Australian monsoonal tropics include vast, ecologically intact savanna‐woodland plains interspersed with ancient sandstone uplands. Although recognized in general for its high species richness and endemism, the biodiversity of the region remains underexplored due to its remoteness. This is despite a high rate of ongoing species discovery, especially in wetter regions and for rock‐restricted taxa. To provide a baseline for ongoing comparative analyses, we tested for phylogeographic structure in an ecologically generalized and widespread taxon, the gecko Heteronotia binoei. We apply coalescent analyses to multilocus sequence data (mitochondrial DNA and eight nuclear DNA introns) from individuals sampled extensively and at fine scale across the region. The results demonstrate surprisingly deep and geographically nested lineage diversity. Several intra‐specific clades previously shown to be endemic to the region were themselves found to contain multiple, short‐range lineages. To infer landscapes with concentrations of unique phylogeographic diversity, we probabilistically estimate the ranges of lineages from point data and then, combining these estimates with the nDNA species tree, estimate phyloendemism across the region. Highest levels of phyloendemism occur in northern Top End, especially on islands, across the topographically complex Arnhem escarpment, and across the sandstone ranges of the western Gulf region. These results drive home that deep phylogeographic structure is prevalent in tropical low‐dispersal taxa, even ones that are ubiquitous across geography and habitats.