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An association between metabolic abnormalities, hypercholesterolemia and affective disorders is now well recognized. Less well understood are the molecular mechanisms, both in brain and in the periphery, that underpin this phenomenon. In addition to hepatic lipid accumulation and inflammation, C57BL/6J mice fed a high-cholesterol diet (0.2%) to induce non-alcoholic fatty liver disease (NAFLD), exhibited behavioral despair, anxiogenic changes, and hyperlocomotion under bright light. These abnormalities were accompanied by increased expression of transcript and protein for Toll-like receptor 4, a pathogen-associated molecular pattern (PAMP) receptor, in the prefrontal cortex and the liver. The behavioral changes and Tlr4 expression were reversed ten days after discontinuation of the high-cholesterol diet. Remarkably, the dietary fat content and body mass of experimental mice were unchanged, suggesting a specific role for cholesterol in the molecular and behavioral changes. Expression of Sert and Cox1 were unaltered. Together, our study has demonstrated for the first time that high consumption of cholesterol results in depression- and anxiety-like changes in C57BL/6J mice and that these changes are unexpectedly associated with the increased expression of TLR4, which suggests that TLR4 may have a distinct role in the CNS unrelated to pathogen recognition. [ABSTRACT FROM AUTHOR]

Abstract: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that is the leading genetic cause of infantile death. SMA is caused by homozygous deletion or mutation of the survival of motor neuron 1 gene (SMN1). The SMN2 gene is nearly identical to SMN1, however is alternatively spliced. The close relationship to SMN1 results in SMN2 being a very power genetic modifier of SMA disease severity and a target for therapies. We sought to identify the regulatory role individual HDAC proteins use to control expression of full length protein from the SMN2 genes. We used quantitative PCR to determine the effects shRNA silencing of individual HDACs on the steady state levels of a SMN2-luciferase reporter transcripts. We determined that reduction of individual HDAC proteins was sufficient to increase SMN protein levels in a transgenic reporter system. Knockdown of class I HDAC proteins preferentially activated the reporter by increased promoter transcription. Silencing of class II HDAC proteins maintained transcriptional activity; however silencing of HDAC 5 and 6 also appeared to enhance inclusion of an alternatively spliced exon. This work highlights HDAC proteins 2 and 6 as excellent investigative targets. These data are important to the basic understanding of SMN expression regulation and the refinements of current therapeutic compounds as well as the development of novel SMA therapeutics. [Copyright &y& Elsevier]

It has been suggested that secondary sexual ornamentation signals male ability to resist infections, as only high-quality individuals are able to invest both in high immune defence and elaborate ornament expression. Such ornaments could thus serve as indicators of male quality and could be used by females in choosing mates. Ostriches are sexually dimorphic with regard to coloration of their feathers, bill, neck and legs, and have a promiscuous mating system, with a high degree of reproductive skew, particularly in males. We investigated the relationship between the coloration of the feathers, bill, neck and legs of 15 male ostriches, maintained in a breeding flock, and the cell-mediated (measured using a phytohaemagglutinin (PHA) injection) and humoral components of their immune systems, as well as their heterophil:lymphocyte ratio. We found that male responses to PHA injection and humoral responses to tetanus were predicted by leg coloration, humoral responses to diphtheria were predicted by white feather coloration, and the heterophil:lymphocyte ratio was related to bill coloration. These traits, which relate to male immune capacity, are exposed during male–male interactions and courtship display, so we suggest that these visual cues could provide valuable information on male quality to females (as well as rival males), forming the basis of mate choice in this species. [Copyright &y& Elsevier]

Life history theory predicts that females should modify their investment in a particular breeding attempt according to the likelihood of its success, as the investment of females in reproduction is typically higher than that of males. The ostrich mating system is promiscuous, and is thus a particularly interesting one in which to investigate differential investment by the sexes. To date, there has been no evidence that female ostriches discriminate between males as potential mates, but the degree of dimorphism in this promiscuous species and the variation in chick size within clutches suggest that differential maternal investment is likely. We investigated the relationship between egg mass and coloration of the feathers, bill, neck and legs of 15 male ostriches, maintained in a breeding flock at an ostrich farm in South Africa. Paternity was determined using microsatellite markers. We found that the colour of the neck, white and black body feathers, and the brightness of black feathers, predicted egg mass. These traits are exposed during the male courtship display, so we suggest that these visual cues influence the degree of maternal investment in eggs through their influence on female perception of mate quality. [Copyright &y& Elsevier]

Examines the effect of testicular size on reproductive behavior of male wrens in Great Britain. Prediction of initiation of nest building by male age and testis size; Relationship of the size of testis to body condition; Increase of breeding attempts by males that initiate early breeding.

Examines the possible aerodynamic effects of increased tail length in male scarlet-tufted malachite sunbirds, Nectarinia johnstoni, and finds that birds with shortened tails spent longer flying and hawked more efficiently than before the manipulation, while birds with lengthened tails spent less time flying and were less efficient at hawking. Possible aerodynamic effects; Study animal and methods; Results; Discussion.

Suggests that the size of pectoral tufts and tail length in male scarlet-tufted malachite sunbirds are influenced by environmental conditions rather than male age. Mediation of male-male competition; Differences in the condition of males; Population tail length; Availability of food.

Presents information on wrens, Troglodytes troglodytes, while focusing on the usefulness of cues in mate choice to females. Evaluation of the information contained in cues used in mate choice; Information on an experiment conducted in 1994; Results of the experiment.

Analyzes the nest building signals in male wrens. Varied designs of ornaments used in mate choice; Predictor of variation in the number of nests constructed; Suggestion on the condition-dependent trait of nest construction ability in male wrens.

• Target enrichment can directly sequence host-associated fungal pathogens. • Fungal pathogen load is positively associated with enrichment success. • Resulting genetic data can identify phylogenetic placements of fastidious strains. • Salamander at US zoo was infected with Asian-origin Batrachochytrium strain. • Method can be applied to other unculturable fungal samples to identify cryptic strains. The chytrid fungus Batrachochytrium dendrobatidis (Bd) was discovered in 1998 as the cause of chytridiomycosis, an emerging infectious disease causing mass declines in amphibian populations worldwide. The rapid population declines of the 1970s-1990s were likely caused by the spread of a highly virulent lineage belonging to the Bd-GPL clade that was introduced to naïve susceptible populations. Multiple genetically distinct and regional lineages of Bd have since been isolated and sequenced, greatly expanding the known biological diversity within this fungal pathogen. To date, most Bd research has been restricted to the limited number of samples that could be isolated using culturing techniques, potentially causing a selection bias for strains that can grow on media and missing other unculturable or fastidious strains that are also present on amphibians. We thus attempted to characterize potentially non-culturable genetic lineages of Bd from distinct amphibian taxa using sequence capture technology on DNA extracted from host tissue and swabs. We focused our efforts on host taxa from two different regions that likely harbored distinct Bd clades: (1) wild-caught leopard frogs (Rana) from North America, and (2) a Japanese Giant Salamander (Andrias japonicus) at the Smithsonian Institution's National Zoological Park that exhibited signs of disease and tested positive for Bd using qPCR, but multiple attempts failed to isolate and culture the strain for physiological and genetic characterization. We successfully enriched for and sequenced thousands of fungal genes from both host clades, and Bd load was positively associated with number of recovered Bd sequences. Phylogenetic reconstruction placed all the Rana -derived strains in the Bd-GPL clade. In contrast, the A. japonicus strain fell within the Bd-Asia3 clade, expanding the range of this clade and generating additional genomic data to confirm its placement. The retrieved ITS locus matched public barcoding data from wild A. japonicus and Bd infections found on other amphibians in India and China, suggesting that this uncultured clade is widespread across Asia. Our study underscores the importance of recognizing and characterizing the hidden diversity of fastidious strains in order to reconstruct the spatiotemporal and evolutionary history of Bd. The success of the sequence capture approach highlights the utility of directly sequencing pathogen DNA from host tissue to characterize cryptic diversity that is missed by culture-reliant approaches. [ABSTRACT FROM AUTHOR]

Perinatal inflammation is known to contribute to neurodevelopmental diseases. Animal models of perinatal inflammation have revealed that the inflammatory response within the brain is age dependent, but the regulators of this variation remain unclear. In the adult, the peripheral acute phase response (APR) is known to be pivotal in the downstream recruitment of leukocytes to the injured brain. The relationship between perinatal brain injury and the APR has not been established. Here, we generated focal inflammation in the brain using interleukin (IL)-1β at postnatal day (P)7, P14, P21 and P56 and studied both the central nervous system (CNS) and hepatic inflammatory responses at 4 h. We found that there is a significant window of susceptibility in mice at P14, when compared to mice at P7, P21 and P56. This was reflected in increased neutrophil recruitment to the CNS, as well as an increase in blood–brain barrier permeability. To investigate phenomena underlying this window of susceptibility, we performed a dose response of IL-1β. Whilst induction of endogenous IL-1β or intercellular adhesion molecule (ICAM)-1 in the brain and induction of a hepatic APR were dose dependent, the recruitment of neutrophils and associated blood–brain barrier breakdown was inversely proportional. Furthermore, in contrast to adult animals, an additional peripheral challenge (intravenous IL-1β) reduced the degree of CNS inflammation, rather than exacerbating it. Together these results suggest a unique window of susceptibility to CNS injury, meaning that suppressing systemic inflammation after brain injury may exacerbate the damage caused, in an age-dependent manner. [ABSTRACT FROM AUTHOR]

Abstract: The existence of consistent individual differences in behavioral strategies (“personalities” or coping styles) has been reported in several animal species. Recent work in great tits has shown that such traits are heritable and exhibit significant genetic variation. Free-living birds respond to environmental stresses by up-regulating corticosterone production. Behavior during mild stress can occur in accordance to two types of coping styles, i.e. active and passive. Using artificially selected lines of zebra finches that vary in the amount of corticosterone produced in response to a manual restraint stressor we ran three “personality” experiments. We show that birds in the different corticosterone lines differ in their exploratory and risk-taking behaviors. There was an increase in exploratory behavior as corticosterone titre increased but only in the low corticosterone line. Birds in high corticosterone line showed greater risk-taking behavior than birds in the other lines. Thus, in general, higher levels of circulating corticosterone following a mild stress result in greater exploratory behavior and greater risk taking. This study shows that lines of animals selected for endocrine hormonal responses differ in their “coping” styles or “personalities”. [Copyright &y& Elsevier]

Abstract: The original immunocompetence handicap hypothesis (ICHH) suggested that testosterone has a handicapping effect in males by both promoting the development of sexual signals and suppressing immune function. A modified version, the stress-linked ICHH, has recently proposed that testosterone is immunosuppressive indirectly by increasing production of corticosterone. To test both the original and stress-mediated versions of the ICHH, we implanted male zebra finches taken from lines selected for divergent maximum stress-induced levels of corticosterone (high, low and control) with either empty or testosterone-filled implants. Their humoral and cell-mediated immune responses were then assessed by challenge with diphtheria:tetanus vaccine and phytohemagglutinin respectively. We found no effect of the hormone manipulations on either PHA or tetanus antibody responses, but found a significant interaction between titers of both testosterone and corticosterone on diphtheria secondary antibody response; antibody response was greatest in individuals with high levels of both hormones. There was also a significant interactive effect between testosterone treatment group and corticosterone titer on body mass; the body mass of males in the elevated testosterone treatment group decreased with increasing corticosterone titer. These results suggest that, contrary to the assumption of the stress-mediated version of the ICHH, high plasma levels of corticosterone are not immunosuppressive, but are in fact immuno-enhancing in the presence of high levels of plasma testosterone. Equally, the central assumption of the ICHH that testosterone is obligately immunosuppressive is also not supported. The same individuals with the highest levels of both hormones and consequently the most robust antibody response also possessed the lowest body mass. [Copyright &y& Elsevier]