Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

You are Not Welcome: Social Exchanges between Female Spider Monkeys (Ateles geoffroyi)

Group living leads to competition for food between group members. Two types of intragroup food competition may occur: scramble competition, in which all group members use the same resource, such that feeding opportunities are equal for everyone; and contest competition, in which some group members monopolize resources through aggression and dominance. In species in which females disperse from the natal group and immigrate into other groups, immigrant females increase group size and thus possibly food competition. Under these circumstances, other females may use aggression to discourage new females from joining the group. We assessed the distribution of aggression, embraces, and kisses among female spider monkeys (Ateles geoffroyi) in relation to group tenure. We recorded social interactions during 1688 10-min focal animal samples on 11 females in Santa Rosa, Costa Rica. We found that aggression was rare between long-term resident females and aggression rates were not higher during feeding than in other contexts, suggesting there was little contest competition. Long-term residents and less recently immigrant females showed higher aggression rates toward the most recent immigrants than toward other females, especially during the first months after a female immigrated, which coincided with the dry season. We did not find similar patterns for embrace and kiss. These results suggest that other females target aggression toward the most recent immigrants to reduce scramble competition. This finding suggests that group tenure should be included in socioecological models for species with female dispersal. © 2017 Springer Science+Business Media, LL

Mood and cognition in healthy older European adults: the Zenith study

YesBackground: The study aim was to determine if state and trait intra-individual measures of everyday affect predict cognitive functioning in healthy older community dwelling European adults (n = 387), aged 55-87 years. Methods: Participants were recruited from centres in France, Italy and Northern Ireland. Trait level and variability in positive and negative affect (PA and NA) were assessed using self-administered PANAS scales, four times a day for four days. State mood was assessed by one PANAS scale prior to assessment of recognition memory, spatial working memory, reaction time and sustained attention using the CANTAB computerized test battery. Results: A series of hierarchical regression analyses were carried out, one for each measure of cognitive function as the dependent variable, and socio-demographic variables (age, sex and social class), state and trait mood measures as the predictors. State PA and NA were both predictive of spatial working memory prior to looking at the contribution of trait mood. Trait PA and its variability were predictive of sustained attention. In the final step of the regression analyses, trait PA variability predicted greater sustained attention, whereas state NA predicted fewer spatial working memory errors, accounting for a very small percentage of the variance (1-2%) in the respective tests. Conclusion: Moods, by and large, have a small transient effect on cognition in this older sample

Non-specific symptoms as clues to changes in emotional well-being

Background: Somatic symptoms are a common reason for visits to the family physician. The aim of this study was to examine the relation between non-specific symptoms and changes in emotional well-being and the degree to which the physician considers the possibility of mental distress when faced with such patients. Methods: Patients who complained of two or more symptoms including headache, dizziness, fatigue or weakness, palpitations and sleep disorders over one year were identified from the medical records of a random sample of 45 primary care physicians. A control group matched for gender and age was selected from the same population. Emotional well-being was assessed using the MOS-SF 36 in both groups. Results: The study group and the control group each contained 110 patients. Completed MOS questionnaires were obtained from 92 patients, 48 patients with somatic symptoms and 44 controls. Sixty percent of the patients with somatic symptoms experienced decreased emotional well being compared to 25% in the control group (p =0.00005). Symptoms of dizziness, fatigue and sleep disturbances were significantly linked with mental health impairments. Primary care physicians identified only 6 of 29 patients (21%) whose responses revealed functional limitations due to emotional problems as suffering from an emotional disorder and only 6 of 23 patients (26%) with a lack of emotional well being were diagnosed with an emotional disorder. Conclusions: Non-specific somatic symptoms may be clues to changes in emotional well-being. Improved recognition and recording of mental distress among patients who complain of these symptoms may enable better follow up and treatment

How can contributors to open-source communities be trusted? On the assumption, inference, and substitution of trust

Open-source communities that focus on content rely squarely on the contributions of invisible strangers in cyberspace. How do such communities handle the problem of trusting that strangers have good intentions and adequate competence? This question is explored in relation to communities in which such trust is a vital issue: peer production of software (FreeBSD and Mozilla in particular) and encyclopaedia entries (Wikipedia in particular). In the context of open-source software, it is argued that trust was inferred from an underlying 'hacker ethic', which already existed. The Wikipedian project, by contrast, had to create an appropriate ethic along the way. In the interim, the assumption simply had to be that potential contributors were trustworthy; they were granted 'substantial trust'. Subsequently, projects from both communities introduced rules and regulations which partly substituted for the need to perceive contributors as trustworthy. They faced a design choice in the continuum between a high-discretion design (granting a large amount of trust to contributors) and a low-discretion design (leaving only a small amount of trust to contributors). It is found that open-source designs for software and encyclopaedias are likely to converge in the future towards a mid-level of discretion. In such a design the anonymous user is no longer invested with unquestioning trust

Deficient of a Clock Gene, Brain and Muscle Arnt-Like Protein-1 (BMAL1), Induces Dyslipidemia and Ectopic Fat Formation

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic β cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome

Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection

Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection.However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5-/-). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5-/- mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5-/- BMDMs.We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs

Attentional Set-Shifting Deficit in Parkinson’s Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study

The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients

Decline of Birds in a Human Modified Coastal Dune Forest Landscape in South Africa

Previous studies demonstrate that old-growth forest remnants and vegetation regenerating after anthropogenic disturbance provide habitat for birds in a human modified coastal dune forest landscape in northern KwaZulu-Natal, South Africa. However, occurrence does not ensure persistence. Based on a 13-year monitoring database we calculated population trends for 37 bird species and general trends in overall bird density in different vegetation types. We evaluated species' characteristics as covariates of population trend and assessed changes in rainfall and proportional area and survey coverage per vegetation type. 76% of species assessed have declined, 57% significantly so at an average rate of 13.9% per year. Overall, bird density has fallen at 12.2% per year across old-growth forest and woody regenerating vegetation types. Changes in proportional area and coverage per vegetation type may partly explain trends for a few species but are unlikely to account for most. Below average rainfall may have contributed to bird declines. However, other possibilities warrant further investigation. Species with larger range extents tended to decline more sharply than did others, and these species may be responding to environmental changes on a broader geographical scale. Our results cast doubt on the future persistence of birds in this human modified landscape. More research is needed to elucidate the mechanisms driving population decline in the study area and to investigate whether the declines identified here are more widespread across the region and perhaps the continent

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4+ clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-γ in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-γ after melanoma stimulation. No CD4+ clones responded to stimulation with recipient haemopoietic cells. The majority of CD8+ clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4+ clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma