Understanding the role of P2X7 in affective disorders—are glial cells the major players?

Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7−/− mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and inflammatory changes have been observed in the brains of P2X7−/− mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain

INTERACTION OF BACILLUS ANTHRACIS EXOSPORIUM PROTEIN BCLA WITH COMPLEMENT FACTOR H AND SPORE PERSISTENCE IN THE LUNG

Anthrax outbreaks in the United States and Europe and its potential use as a bioweapon have made Bacillus anthracis an interest of study. Anthrax infections are caused by the entry of B. anthracis spores into the host via the respiratory system, the gastrointestinal tract, cuts or wounds in the skin, and injection. Among these four forms, inhalational anthrax has the highest lethality rate and persistence of spores in the lungs of animals following pulmonary exposure has been noted for decades. However, details or mechanisms of spore persistence were not known. In this study, we investigated spore persistence in a mouse model. The results suggest that B. anthracis spores have special properties that promote persistence in the lung, and that there may be multiple mechanisms contributing to spore persistence. Moreover, recent discoveries from our laboratory suggest that spores evolved a sophisticated mechanism to interact with the host complement system. The complement system is a crucial part of the host defense mechanism against foreign microorganisms. Knowledge of the specific interactions that occur between the complement system and B. anthracis was limited. Studies performed in our laboratory have suggested that spores of B. anthracis can target specific proteins, such as Factor H (fH) of the complement system. Spores of B. anthracis are enclosed by an exosporium, which consists of a basal layer surrounded by a nap of hair-like filaments. The major structural component of the filaments is called Bacillus collagen-like protein of anthracis (BclA), which comprises a central collagen-like region and a globular C-terminal domain. BclA is the first point of contact with the innate system of an infected host. In this study, we investigated the molecular details of BclA-fH interaction with respect to the specific binding mechanism and the functional significance of this interaction in a murine model of anthrax infection. We hypothesized that the recruitment of fH to the spore surface by BclA limits the extent of complement activation and promotes pathogen survival and persistence in the infected host. Findings from this study are significant to understanding how to treat post-exposure prophylaxis and improve our knowledge of spores with the host immune system

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing in Persons with Mild Cognitive Impairment

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD performed an emotionally-valenced short-term memory task while encephalography was recorded. Results indicated that for persons with MCI, high arousal negative stimuli led to working memory processing patterns previously associated with MCI presumed due to AD and dementia of the Alzheimer-type. In contrast, low arousal positive stimuli evoked a processing pattern similar to MCI participants’ unaffected spouses. Our current findings suggest that low arousal positive stimuli attenuate working memory deficits of MCI due to AD

Examining Neolithic Building and Activity Areas through Historic Cultural Heritage in Jordan: A Combined Ethnographic, Phytolith and Geochemical Investigation

The INEA project (Identifying activity areas in Neolithic sites through Ethnographic Analysis of phytoliths and geochemical residues, https://research.bournemouth. ac.uk/2014/07/inea-project-2/) develops and applies a method that combines the analysis of plant remains (silica phytoliths) and geochemical residues to inform on construction methods and the use of space in recently abandoned historical villages and Neolithic settlements. It is a collaborative project based at Bournemouth University, in partnership with the Council for British Research in the Levant

“Righteous Minds” in Health Care: Measurement and Explanatory Value of Social Intuitionism in Accounting for the Moral Judgments in a Sample of U.S. Physicians

The broad diversity in physicians’ judgments on controversial health care topics may reflect differences in religious characteristics, political ideologies, and moral intuitions. We tested an existing measure of moral intuitions in a new population (U.S. physicians) to assess its validity and to determine whether physicians’ moral intuitions correlate with their views on controversial health care topics as well as other known predictors of these intuitions such as political affiliation and religiosity. In 2009, we mailed an 8-page questionnaire to a random sample of 2000 practicing U.S. physicians from all specialties. The survey included the Moral Foundations Questionnaire (MFQ30), along with questions on physicians’ judgments about controversial health care topics including abortion and euthanasia (no moral objection, some moral objection, strong moral objection). A total of 1032 of 1895 (54%) physicians responded. Physicians’ overall mean moral foundations scores were 3.5 for harm, 3.3 for fairness, 2.8 for loyalty, 3.2 for authority, and 2.7 for sanctity on a 0–5 scale. Increasing levels of religious service attendance, having a more conservative political ideology, and higher sanctity scores remained the greatest positive predictors of respondents objecting to abortion (β = 0.12, 0.23, 0.14, respectively, each p<0.001) as well as euthanasia (β = 0.08, 0.17, and 0.17, respectively, each p<0.001), even after adjusting for demographics. Higher authority scores were also significantly negatively associated with objection to abortion (β = −0.12, p<0.01), but not euthanasia. These data suggest that the relative importance physicians place on the different categories of moral intuitions may predict differences in physicians’ judgments about morally controversial topics and may interrelate with ideology and religiosity. Further examination of the diversity in physicians’ moral intuitions may prove illustrative in describing and addressing moral differences that arise in medical practice.</p

The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production.

In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (MΦ) from MR(-/-) mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR(-/-) mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFNγ but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFNγ

Chronic Oral Exposure to Bisphenol A Results in a Nonmonotonic Dose Response in Mammary Carcinogenesis and Metastasis in MMTV-erbB2 Mice

Background: Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. BPA can leach from these products in appreciable amounts, resulting in nearly ubiquitous daily exposure to humans. Whether BPA is harmful to humans, especially when administered orally in concentrations relevant to humans, is a topic of debate

Plasma evolution within an erupting coronal cavity

Coronal cavities have previously been observed associated with long-lived quiescent filaments and are thought to correspond to the associated magnetic flux rope. Although the standard flare model predicts a coronal cavity corresponding to the erupting flux rope, these have only been observed using broadband imaging data, restricting analysis to the plane-of-sky. We present a unique set of spectroscopic observations of an active region filament seen erupting at the solar limb in the extreme ultraviolet (EUV). The cavity erupted and expanded rapidly, with the change in rise phase contemporaneous with an increase in non-thermal electron energy flux of the associated flare. Hot and cool filamentary material was observed to rise with the erupting flux rope, disappearing suddenly as the cavity appeared. Although strongly blue-shifted plasma continued to be observed flowing from the apex of the erupting flux rope, this outflow soon ceased. These results indicate that the sudden injection of energy from the flare beneath forced the rapid eruption and expansion of the flux rope, driving strong plasma flows which resulted in the eruption of an under-dense filamentary flux rope.Comment: 11 pages, 5 figures. Accepted for publication in The Astrophysical Journa

Limiting Pseudomonas aeruginosa Biofilm Formation Using Cold Atmospheric Pressure Plasma

We investigate the ability to disrupt and limit growth biofilms of Pseudomonas aeruginosa using application of cold atmospheric pressure (CAP) plasma. The effect of the bio-film's exposure to a helium (CAP) jet was assessed at varying time points during biofilm maturation. Results showed that the amount of time during biofilm growth that CAP pressure was applied has a crucial role on the ability of biofilms to mature and recover after CAP exposure. Intervention during the early stages of biofilm formation (0-8 h) results in a 4-5-log reduction in viable bacterial cells (measured at 24 h of incubation) relative to untreated biofilms. However, CAP treatment of biofilm at 12 h and above only results in a 2-log reduction in viable cells. This has potentially important implications for future clinical application of CAP to treat infected wounds