Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Traditional health practitioners' perceptions, herbal treatment and management of HIV and related opportunistic infections

Background: In South Africa, traditional health practitioners? (THPs) explanatory frameworks concerning illness aetiologies are much researched. However there is a gap in the literature on how THPs understand HIV-related opportunistic infections (OIs), i.e. tuberculosis, candidiasis and herpes zoster. This study aimed to comprehend THPs? understandings of the aforementioned; to ascertain and better understand the treatment methods used by THPs for HIV and OIs, while also contributing to the documentation of South African medicinal plants for future conservation. Methods: The study was conducted in two locations: Strand, Western Cape where THPs are trained and Mpoza village, Mount Frere, Eastern Cape from where medicinal plants are ordered or collected. Semi-structured interviews were conducted with 53 THPs of whom 36 were diviners (amagrirha: isangoma) and 17 herbalists (inyanga). THPs were selected through a non-probability ?snowball? method. Data were analysed using a thematic content analysis approach. An ethnobotanical survey was conducted and plants used to manage HIV and OIs were collected. A complete set of voucher specimens was deposited at the University of the Western Cape Herbarium for identification. Plant names were checked and updated with Kew?s online website http://www.theplantlist.org. Results: THPs conceptualise the aetiology of HIV and OIs at two related levels. The first involves the immediate manifestation of the illness/condition because of a viral infection in the blood (HIV), the presence of bacteria in the lungs (tuberculosis), or weakened state of the body making it susceptible to OIs. The presence of OIs is indicative of the probable presence of HIV. The second level of causation affects the first, which includes pollution, changes in cultural sexual norms, witchcraft, environmental factors, and lack of adherence to ancestral rituals. THPs reported using 17 plants belonging to 12 families. Remedies included mixes of up to five plants. Conclusion: This study explored the THPs? perspectives on HIV and commonly associated OIs and their herbal treatment methods. THPs generally rely on biomedical diagnosis before treating a client. They also seek guidance from the ancestors for a particular diagnosis, the plants to use for a specific treatment, when to harvest, and how to administer herbal remedies

Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an established model of γ-herpesvirus infection. We have previously developed an alternative system using a natural host, the wood mouse (Apodemus sylvaticus), and shown that the MHV-68 M3 chemokine-binding protein contributes significantly to MHV-68 pathogenesis. Here we demonstrate in A. sylvaticus using high-density micro-arrays that M3 influences the expression of genes involved in the host response including Scgb1a1 and Bpifa1 that encode potential innate defense proteins secreted into the respiratory tract. Further analysis of MHV-68-infected animals showed that the levels of both protein and RNA for SCGB1A1 and BPIFA1 were decreased at day 7 post infection (p.i.) but increased at day 14 p.i. as compared with M3-deficient and mock-infected animals. The modulation of expression was most pronounced in bronchioles but was also present in the bronchi and trachea. Double staining using RNA in situ hybridization and immunohistology demonstrated that much of the BPIFA1 expression occurs in club cells along with SCGB1A1 and that BPIFA1 is stored within granules in these cells. The increase in SCGB1A1 and BPIFA1 expression at day 14 p.i. was associated with the differentiation of club cells into mucus-secreting cells. Our data highlight the role of club cells and the potential of SCGB1A1 and BPIFA1 as innate defense mediators during respiratory virus infection

Toxicity of mercury to hybridoma TA7 cells

Environmental mercury and mercury compound contamination has increased dramatically since the industrial revolution. This paper describes the toxic effects of mercury on a culture of hybridoma TA7 cells, which produce antibodies against the A-subunit of viskumin. Cells were cultivated on 96- well flat-bottomed plates with RPMI-1640 medium supplemented with 10% fetal calf serum at 37°C in 5% CO2/95% air. The cells were exposed to 0.1nM/l- 10μM/l Hg2(NO3)2·2H2O (mercury nitrate) during the exponential growth phase. Toxicity was assessed by using the colorimetric MTT (tetrazolium) assay after exposure for 48 hours. Cell growth and cell survival were evaluated by using percentage indices of cellular content in exposed cells when compared to non-exposed control cells. The concentrations of the no- effect level, the lowest observed effect level and the the highest toxic effect level were registered. The toxic effects of the mercury compound on the hybridoma cells occurred between 0.1μM/l and 10μM/l.Peer reviewe

Solar Flares and Coronal Mass Ejections: A Statistically Determined Flare Flux-CME Mass Correlation

In an effort to examine the relationship between flare flux and corresponding CME mass, we temporally and spatially correlate all X-ray flares and CMEs in the LASCO and GOES archives from 1996 to 2006. We cross-reference 6,733 CMEs having well-measured masses against 12,050 X-ray flares having position information as determined from their optical counterparts. For a given flare, we search in time for CMEs which occur 10-80 minutes afterward, and we further require the flare and CME to occur within +/-45 degrees in position angle on the solar disk. There are 826 CME/flare pairs which fit these criteria. Comparing the flare fluxes with CME masses of these paired events, we find CME mass increases with flare flux, following an approximately log-linear, broken relationship: in the limit of lower flare fluxes, log(CME mass)~0.68*log(flare flux), and in the limit of higher flare fluxes, log(CME mass)~0.33*log(flare flux). We show that this broken power-law, and in particular the flatter slope at higher flare fluxes, may be due to an observational bias against CMEs associated with the most energetic flares: halo CMEs. Correcting for this bias yields a single power-law relationship of the form log(CME mass)~0.70*log(flare flux). This function describes the relationship between CME mass and flare flux over at least 3 dex in flare flux, from ~10^-7 to 10^-4 W m^-2.Comment: 28 pages, 16 figures, accepted to Solar Physic

The Alexander-Orbach conjecture holds in high dimensions

We examine the incipient infinite cluster (IIC) of critical percolation in regimes where mean-field behavior has been established, namely when the dimension d is large enough or when d>6 and the lattice is sufficiently spread out. We find that random walk on the IIC exhibits anomalous diffusion with the spectral dimension d_s=4/3, that is, p_t(x,x)= t^{-2/3+o(1)}. This establishes a conjecture of Alexander and Orbach. En route we calculate the one-arm exponent with respect to the intrinsic distance.Comment: 25 pages, 2 figures. To appear in Inventiones Mathematica

Exploring the Reported Strengths and Limitations of Aboriginal and Torres Strait Islander Health Research: A Narrative Review of Intervention Studies

High quality intervention research is needed to inform evidence-based practice and policy for Aboriginal and Torres Strait Islander communities. We searched for studies published from 2008–2020 in the PubMed database. A narrative review of intervention literature was conducted, where we identified researcher reported strengths and limitations of their research practice. A total of 240 studies met inclusion criteria which were categorised as evaluations, trials, pilot interventions or implementation studies. Reported strengths included community engagement and partnerships; sample qualities; Aboriginal and Torres Strait Islander involvement in research; culturally appropriate and safe research practice; capacity building efforts; providing resources or reducing costs for services and communities; understanding local culture and context; and appropriate timelines for completion. Reported limitations included difficulties achieving the target sample size; inadequate time; insufficient funding and resources; limited capacity of health workers and services; and inadequate community involvement and communication issues. This review highlights that community consultation and leadership coupled with appropriate time and funding, enables Aboriginal and Torres Strait Islander health intervention research to be conducted. These factors can enable effective intervention research, and consequently can help improve health and wellbeing outcomes for Aboriginal and Torres Strait Islander people.Romany McGuffog, Jamie Bryant, Kade Booth, Felicity Collis, Alex Brown, Jaquelyne T. Hughes, Catherine Chamberlain, Alexandra McGhie, Breanne Hobden, and Michelle Kenned

Capture cross sections from (p,d) reactions

Cross sections for compound-nuclear reactions involving unstable targets are important for many applications, but can often not be measured directly. Several indirect methods have been proposed to determine neutron capture cross sections for unstable isotopes. We consider an approach that aims at constraining statistical calculations of capture cross sections with data obtained from light-ion transfer reactions such as (p,d). We discuss the theoretical descriptions that have to be developed in order to extract meaningful cross section constraints from such data and show some benchmark results