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The primary objective of this study was to delineate classes of individuals based on depression trajectories from the antenatal period through 54-month postpartum and internal and external resources that are associated with low depression risk. Participants came from the Growing Up in New Zealand (GUiNZ) study (n = 5664), which is a pregnancy cohort study and is nationally representative of the ethnic and socioeconomic diversity of contemporary New Zealand births. Growth curve mixture modeling was used to identify distinct subgroups based on depression scores from the antenatal period through 54-month postpartum. Logistic regression models were run to investigate socioeconomic factors and internal and external resources that were associated with depression class membership. A two-class model, "low risk" and "high risk," resulted in the best model fit. Most of the sample (n = 5110, 90%) fell into the "low-risk" class defined by no-to-mild depression symptoms during pregnancy and decreasing depressive symptoms over time (bintercept = - .05, bslope = - .05). Approximately 10% of the sample fell into the "high-risk" class (n = 554, 10%) defined by mild-to-moderate depressive symptoms during pregnancy and increasing depressive symptomology over time (bintercept = .39, bslope = .57). More positive parenting-related attitudes, better pre-pregnancy self-reported health, informal social supports, and community belonging were significantly associated with greater odds of being in the "low-risk" class, after controlling for socioeconomic factors. These findings suggest that targeting internal and external resources for individuals across the perinatal and early childhood periods is important to mitigating maternal depression.

Additional file 1.

This paper describes three models of learning theories, derives optimal presentation strategies for the models, and compares the effectiveness of the strategies in two computer assisted instruction experiments. The three models described are: 1) the linear, or response-insensitive model, in which the error probability for a given item depends on the number of times it has been presented; 2) the all-or-none model, in which the error probability for a given item depends on the number of times it has been answered correctly; and 3) the random-trial increments (RTI) model, which is a compromise between the linear and the all-or-none model. One of the computer assisted instruction experiments reviewed compared the strategy derived from the linear model with the all-or-none strategy and found that the all-or-none strategy accounted for significantly higher scores on both immediate and delayed posttests. The second experiment compared all three strategies, and found the RTI strategy to be most effective. The paper recommends the formulation of other learning models which would take into account different variables. (RT)

The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as antigenic drift. We recently confirmed that a small set of amino acid residues are largely responsible for driving antigenic drift in swine-origin H3 IAV. All identified residues are located adjacent to the HA receptor binding site (RBS), suggesting that substitutions associated with antigenic drift may also influence receptor binding. Among those substitutions, residue 145 was shown to be a major determinant of antigenic evolution. To determine whether there are functional constraints to substitutions near the RBS and their impact on receptor binding and antigenic properties, we carried out site-directed mutagenesis experiments at the single-amino-acid level. We generated a panel of viruses carrying substitutions at residue 145 representing all 20 amino acids. Despite limited amino acid usage in nature, most substitutions at residue 145 were well tolerated without having a major impact on virus replication in vitro. All substitution mutants retained receptor binding specificity, but the substitutions frequently led to decreased receptor binding. Glycan microarray analysis showed that substitutions at residue 145 modulate binding to a broad range of glycans. Furthermore, antigenic characterization identified specific substitutions at residue 145 that altered antibody recognition. This work provides a better understanding of the functional effects of amino acid substitutions near the RBS and the interplay between receptor binding and antigenic drift.

CD33 is an immunomodulatory receptor linked to Alzheimer’s disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo — including aggregated Aβ1–42 — is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility., Abhishek Bhattacherjee et al. investigate the functional differences between human and mouse CD33, an immunomodulatory receptor linked to Alzheimer’s disease. They find that loss of mouse CD33 does not affect cargo uptake in macrophages in contrast to human CD33, which represses phagocytosis when expressed in cells or mice.

Viruses exploit molecules on the target membrane as receptors for attachment and entry into host cells. Thus, receptor expression patterns can define viral tissue tropism and might to some extent predict the susceptibility of a host to a particular virus. Previously, others and we have shown that respiratory pathogens of the genus Gammacoronavirus , including chicken infectious bronchitis virus (IBV), require specific α2,3-linked sialylated glycans for attachment and entry. Here, we studied determinants of binding of enterotropic avian gammacoronaviruses, including turkey coronavirus (TCoV), guineafowl coronavirus (GfCoV), and quail coronavirus (QCoV), which are evolutionarily distant from respiratory avian coronaviruses based on the viral attachment protein spike (S1). We profiled the binding of recombinantly expressed S1 proteins of TCoV, GfCoV, and QCoV to tissues of their respective hosts. Protein histochemistry showed that the tissue binding specificity of S1 proteins of turkey, quail, and guineafowl CoVs was limited to intestinal tissues of each particular host, in accordance with the reported pathogenicity of these viruses in vivo . Glycan array analyses revealed that, in contrast to the S1 protein of IBV, S1 proteins of enteric gammacoronaviruses recognize a unique set of nonsialylated type 2 poly- N -acetyl-lactosamines. Lectin histochemistry as well as tissue binding patterns of TCoV S1 further indicated that these complex N-glycans are prominently expressed on the intestinal tract of various avian species. In conclusion, our data demonstrate not only that enteric gammacoronaviruses recognize a novel glycan receptor but also that enterotropism may be correlated with the high specificity of spike proteins for such glycans expressed in the intestines of the avian host. IMPORTANCE Avian coronaviruses are economically important viruses for the poultry industry. While infectious bronchitis virus (IBV), a respiratory pathogen of chickens, is rather well known, other viruses of the genus Gammacoronavirus , including those causing enteric disease, are hardly studied. In turkey, guineafowl, and quail, coronaviruses have been reported to be the major causative agent of enteric diseases. Specifically, turkey coronavirus outbreaks have been reported in North America, Europe, and Australia for several decades. Recently, a gammacoronavirus was isolated from guineafowl with fulminating disease. To date, it is not clear why these avian coronaviruses are enteropathogenic, whereas other closely related avian coronaviruses like IBV cause respiratory disease. A comprehensive understanding of the tropism and pathogenicity of these viruses explained by their receptor specificity and receptor expression on tissues was therefore needed. Here, we identify a novel glycan receptor for enteric avian coronaviruses, which will further support the development of vaccines.