Entertaining a False Reality: A social comparison examination of beauty pageant participation and the effect on body dissatisfaction, depression, and self-esteem

This study investigated the effects of beauty pageant participation on body dissatisfaction, depression, and self-esteem among women. A group of 20 women who participated in reality show beauty pageants as adults was compared with another group of 20 women who had never participated in beauty pageants. Pageant participants scored higher on body dissatisfaction as well as self-esteem. Neither group had mean depression scores in the clinically significant range. These findings suggest that beauty pageant participation among young adult women may influence their body dissatisfaction and self-esteem but may not have a significant effect on depression

Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from pro-inflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only (APPSw) and amyloid deposits with progression to tau pathology and neuron loss [APPSw/NOS2−/− (nitric oxide synthase 2−/−)]. We also examined tissues from previously published immunotherapy studies. These studies were a passive immunization study in APPSw mice and an active vaccination study in APPSw/NOS2−/− mice. Both studies have already been shown to lower amyloid load and improve cognition. We have found that amyloid deposition is associated with high expression of alternative activation and acquired deactivation genes and low expression of pro-inflammatory genes, whereas disease progression is associated with a mixed phenotype including increased levels of some classical activation factors. Immunotherapy targeting amyloid deposition in both mouse models resulted in decreased alternative inflammatory markers and, in the case of passive immunization, a transient increase in pro-inflammatory markers. Our results suggest that an alternative immune response favours retention of amyloid deposits in the brain, and switching away from this state by immunotherapy permits removal of amyloid

Mitotic Recombination and Rapid Genome Evolution in the Invasive Forest Pathogen Phytophthora ramorum

Invasive alien species often have reduced genetic diversity and must adapt to new environments. Given the success of many invasions, this is sometimes called the genetic paradox of invasion. Phytophthora ramorum is invasive, limited to asexual reproduction within four lineages, and presumed clonal. It is responsible for sudden oak death in the United States, sudden larch death in Europe, and ramorum blight in North America and Europe. We sequenced the genomes of 107 isolates to determine how this pathogen can overcome the invasion paradox. Mitotic recombination (MR) associated with transposons and low gene density has generated runs of homozygosity (ROH) affecting 2,698 genes, resulting in novel genotypic diversity within the lineages. One ROH enriched in effectors was fixed in the NA1 lineage. An independent ROH affected the same scaffold in the EU1 lineage, suggesting an MR hot spot and a selection target. Differences in host infection between EU1 isolates with and without the ROH suggest that they may differ in aggressiveness. Non-core regions (not shared by all lineages) had signatures of accelerated evolution and were enriched in putative pathogenicity genes and transposons. There was a striking pattern of gene loss, including all effectors, in the non-core EU2 genome. Positive selection was observed in 8.0% of RxLR and 18.8% of Crinkler effector genes compared with 0.9% of the core eukaryotic gene set. We conclude that the P. ramorum lineages are diverging via a rapidly evolving non-core genome and that the invasive asexual lineages are not clonal, but display genotypic diversity caused by MR

Lithium Treatment of APPSwDI/NOS2−/− Mice Leads to Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition and Altered Inflammatory Phenotype

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2−/− mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2−/− mice for a period of eight months, followed by water maze testing at 12 months of age, immediately prior to sacrifice. We found that lithium significantly lowered hyperphosphorylated tau levels as measured by Western blot and immunocytochemistry. However, we found no apparent neuroprotection, no effect on spatial memory deficits and an increase in histological amyloid deposition. Aβ levels measured biochemically were unaltered. We also found that lithium significantly altered the neuroinflammatory phenotype of the brain, resulting in enhanced alternative inflammatory response while concurrently lowering the classical inflammatory response. Our data suggest that lithium may be beneficial for the treatment of tauopathies but may not be beneficial for the treatment of Alzheimer's disease

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8− Positive (AT8+) Tau in Alzheimer’s Disease

Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer’s disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 ( RSAD1 ) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. APOE4 vs APOE3 genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals

Diverse Inflammatory Responses in Transgenic Mouse Models of Alzheimer\u27s Disease and the Effect of Immunotherapy on These Responses

While the presence of an inflammatory response in AD (Alzheimer\u27s disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only (APPSw) and amyloid deposits with progression to tau pathology and neuron loss [APPSw/NOS2–/– (nitric oxide synthase 2–/–)]. We also examined tissues from previously published immunotherapy studies. These studies were a passive immunization study in APPSw mice and an active vaccination study in APPSw/NOS2–/– mice. Both studies have already been shown to lower amyloid load and improve cognition. We have found that amyloid deposition is associated with high expression of alternative activation and acquired deactivation genes and low expression of pro-inflammatory genes, whereas disease progression is associated with a mixed phenotype including increased levels of some classical activation factors. Immunotherapy targeting amyloid deposition in both mouse models resulted in decreased alternative inflammatory markers and, in the case of passive immunization, a transient increase in pro-inflammatory markers. Our results suggest that an alternative immune response favours retention of amyloid deposits in the brain, and switching away from this state by immunotherapy permits removal of amyloid

Lithium treatment reduces the levels of abnormally phosphorylated tau protein in APPSwDI/NOS2−/− mice.

<p>Panel A shows representative Western blot images for AT8, AT180 and ß-actin for APPSwDI/NOS2−/− mice receiving either lithium diet (L) or control diet (C). Panel B shows the relative quantification of the band intensity for AT8 and AT180 normalized to the ß-actin band. N = 11 lithium treated mice, N = 8 control treated mice. ** indicates P<0.01 when compared to control treated mice. Panels C and D show immunocytochemistry for AT8 in the frontal cortex region of APPSwDI/NOS2-/mice receiving control diet (C) or lithium supplemented diet (D) for 8 months. Scale bar in D for C and D = 50 µm.</p

Lithium significantly alters the inflammatory state of the APPSwDI/NOS2−/− mouse brain.

<p>Panels A and B show relative gene expression changes of classical inflammatory genes (A) and alternative inflammatory genes (B) in wildtype mice and APPSwDI/NOS2−/− mice receiving either control or lithium diet. Data are shown as fold change compared to the mean of the wildtype mice. ** indicates P<0.01 when compared to wildtype expression. # indicates P<0.05 when compared to APPSwDI/NOS2−/− mice receiving control diet.</p

Microglial activation is reduced following lithium treatment.

<p>Panels A and B show CD11b immunocytochemistry in the hippocampus of APPSwDI/NOS2−/− mice receiving either control diet (A) or lithium diet (B) for 8 months. Scale bar in panel A for A and B = 120 µm. Panel C shows quantification of the percent area occupied by positive stain for CD11b in the frontal cortex and hippocampus. Panels D and E show CD45 immunocytochemistry in the hippocampus of APPSwDI/NOS2−/− mice receiving either control diet (D) or lithium diet (E) for 8 months. Scale bar in panel D for D and E = 120 µm. Panel F shows quantification of the percent area occupied by positive stain for CD45 in the frontal cortex and hippocampus. * indicates P<0.05 and ** indicates P<0.01 when compared to APSPwDI/NOS2−/− mice receiving control diet.</p