Host-associated helminth diversity and microbiome composition contribute to anti-pathogen defences in tropical frogs impacted by forest fragmentation.

Habitat fragmentation can negatively impact wildlife populations by simplification of ecological interactions, but little is known about how these impacts extend to host-associated symbiotic communities. The symbiotic communities of amphibians play important roles in anti-pathogen defences, particularly against the amphibian chytrid fungus (). In this study, we analyse the role of macroparasitic helminth communities in concert with microbial communities in defending the host against infection within the context of forest fragmentation.

Linking microbiome and stress hormone responses in wild tropical treefrogs across continuous and fragmented forests.

The amphibian skin microbiome is an important component of anti-pathogen defense, but the impact of environmental change on the link between microbiome composition and host stress remains unclear. In this study, we used radiotelemetry and host translocation to track microbiome composition and function, pathogen infection, and host stress over time across natural movement paths for the forest-associated treefrog, Boana faber. We found a negative correlation between cortisol levels and putative microbiome function for frogs translocated to forest fragments, indicating strong integration of host stress response and anti-pathogen potential of the microbiome.

Broad host susceptibility of North American amphibian species to Batrachochytrium salamandrivorans suggests high invasion potential and biodiversity risk.

Batrachochytrium salamandrivorans (Bsal) is a fungal pathogen of amphibians that is emerging in Europe and could be introduced to North America through international trade or other pathways. To evaluate the risk of Bsal invasion to amphibian biodiversity, we performed dose-response experiments on 35 North American species from 10 families, including larvae from five species. We discovered that Bsal caused infection in 74% and mortality in 35% of species tested.

The adaptive microbiome hypothesis and immune interactions in amphibian mucus.

The microbiome is known to provide benefits to hosts, including extension of immune function. Amphibians are a powerful immunological model for examining mucosal defenses because of an accessible epithelial mucosome throughout their developmental trajectory, their responsiveness to experimental treatments, and direct interactions with emerging infectious pathogens. We review amphibian skin mucus components and describe the adaptive microbiome as a novel process of disease resilience where competitive microbial interactions couple with host immune responses to select for functions beneficial to the host.

Responsible biosecurity and risk mitigation for laboratory research on emerging pathogens of amphibians.

The increasing study of emerging wildlife pathogens and a lack of policy or legislation regulating their translocation and use has heightened concerns about laboratory escape, species spillover, and subsequent epizootics among animal populations. Responsible self-regulation by research laboratories, in conjunction with institutional-level safeguards, has an important role in mitigating pathogen transmission and spillover, as well as potential interspecies pathogenesis. A model system in disease ecology that highlights these concerns and related amelioration efforts is research focused on amphibian emerging infectious diseases.

Metabolic support of tumour-infiltrating regulatory T cells by lactic acid.

Regulatory T (T) cells, although vital for immune homeostasis, also represent a major barrier to anti-cancer immunity, as the tumour microenvironment (TME) promotes the recruitment, differentiation and activity of these cells. Tumour cells show deregulated metabolism, leading to a metabolite-depleted, hypoxic and acidic TME, which places infiltrating effector T cells in competition with the tumour for metabolites and impairs their function. At the same time, T cells maintain a strong suppression of effector T cells within the TME.

Publisher Correction: Host-associated microbiomes are predicted by immune system complexity and climate.

Following publication of the original paper [1], it was reported that an error in the processing of Fig. 8 occurred. In the online HTML version of the article, Fig.

Host-associated microbiomes are predicted by immune system complexity and climate.

Background: Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function.

Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia.

Blockade of the coinhibitory checkpoint molecule PD-1 has emerged as an effective treatment for many cancers, resulting in remarkable responses. However, despite successes in the clinic, most patients do not respond to PD-1 blockade. Metabolic dysregulation is a common phenotype in cancer, but both patients and tumors are metabolically heterogeneous.

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction.

Although tumor-specific T cells recognize cancer cells, they are often rendered dysfunctional due to an immunosuppressive microenvironment. Here we showed that T cells demonstrated persistent loss of mitochondrial function and mass when infiltrating murine and human tumors, an effect specific to the tumor microenvironment and not merely caused by activation. Tumor-infiltrating T cells showed a progressive loss of PPAR-gamma coactivator 1α (PGC1α), which programs mitochondrial biogenesis, induced by chronic Akt signaling in tumor-specific T cells.

Quantification of Colonic Stem Cell Mutations.

The ability to measure stem cell mutations is a powerful tool to quantify in a critical cell population if, and to what extent, a chemical can induce mutations that potentially lead to cancer. The use of an enzymatic assay to quantify stem cell mutations in the X-linked glucose-6-phosphate dehydrogenase gene has been previously reported.(1) This method requires the preparation of frozen sections and incubation of the sectioned tissue with a reaction mixture that yields a blue color if the cells produce functional glucose-6-phosphate dehydrogenase (G6PD) enzyme.

Colon carcinogenesis in wild type and immune compromised mice after treatment with azoxymethane, and azoxymethane with dextran sodium sulfate.

The association between inflammation and the risk of colorectal cancer (CRC) is well documented in animal models and in humans, but the mechanistic role of inflammation in CRC is less well understood. To address this question, the induction of colon tumors was evaluated in (i) wild type (WT) and athymic BALB/c mice treated with the colon carcinogen azoxymethane (AOM) as a single agent, and (ii) in an inflammation model of colon cancer employing AOM and dextran sodium sulfate (DSS) in WT, athymic, TCRβ(-/-) , TCRδ(-/-) and TCRβ(-/-) TCRδ(-/-) C57Bl/6 mice. The athymic BALB/c mice treated with only AOM developed 90% fewer tumors than the WT mice.

T-cells enhance stem cell mutagenesis in the mouse colon.

A role of inflammation in the etiology of cancer is attributed to the production of reactive oxygen/nitrogen species that can damage DNA. To test this hypothesis, we determined the mutation frequency (MF) in colonic stem cells in C57Bl/6 mice exposed to azoxymethane (AOM), dextran sulfate sodium (DSS) and a combination of AOM and DSS (AOM+DSS). AOM+DSS efficiently and rapidly produces colon tumors in B6 mice.

The effect of 24R,25-(OH)(2)D(3) on protein kinase C activity in chondrocytes is mediated by phospholipase D whereas the effect of 1alpha,25-(OH)(2)D(3) is mediated by phospholipase C.

1alpha,25-(OH)(2)D(3) regulates protein kinase C (PKC) activity in growth zone chondrocytes by stimulating increased phosphatidylinositol-specific phospholipase C (PI-PLC) activity and subsequent production of diacylglycerol (DAG). In contrast, 24R,25-(OH)(2)D(3) regulates PKC activity in resting zone (RC) cells, but PLC does not appear to be involved, suggesting that phospholipase D (PLD) may play a role in DAG production. In the present study, we examined the role of PLD in the physiological response of RC cells to 24R,25-(OH)(2)D(3) and determined the role of phospholipases D, C, and A(2) as well as G-proteins in mediating the effects of vitamin D(3) metabolites on PKC activity in RC and GC cells.

Regulation of phospholipase D (PLD) in growth plate chondrocytes by 24R,25-(OH)2D3 is dependent on cell maturation state (resting zone cells) and is specific to the PLD2 isoform.

Many of the effects of 1alpha,25-(OH)2D3 and 24R,25-(OH)2D3 on costochondral chondrocytes are mediated by the protein kinase C (PKC) signal transduction pathway. 1alpha,25-(OH)2D3 activates PKC in costochondral growth zone chondrocytes through a specific membrane receptor (1alpha,25-mVDR), involving rapid increases in diacylglycerol via a phospholipase C (PLC)-dependent mechanism. 24R,25-(OH)2D3 activates PKC in resting zone chondrocytes.

Internal quality assurance in a clinical virology laboratory. II. Internal quality control.

Aims: In April 1991 additional quality control procedures were introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. Internal quality control (IQC) samples were gradually included in the serological assays performed in the laboratory and supplemented kit controls and standard sera.

Methods: From April 1991 to December 1993, 2421 IQC procedures were carried out with reference sera.

Internal quality assurance in a clinical virology laboratory. I. Internal quality assessment.

Aims: In April 1991 an internal quality assessment scheme (IQAS) was introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. The IQAS was established to identify recurring technical and procedural problems, to check the adequacy of current techniques, and to calculate the frequency of errors.

Methods: Between April 1991 and December 1993, 715 anonymous clinical serum samples were submitted to the laboratory to test 3245 individual procedures of diagnostic viral serology.

Streptococci from primary isolation plates grouped by reverse passive haemagglutination.

Reverse passive haemagglutination, a novel microtitre based assay, was compared with the Streptex (Wellcome UK) latex slide agglutination kit for streptococcal grouping in a diagnostic microbiology laboratory. Three hundred and fifty two extracts from 349 consecutive primary isolation plates were assayed by both methods. Reverse passive haemagglutination gave identical grouping results for 98.

Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily.

A bone-inductive protein has been purified from bovine bone and designated as osteogenic protein (OP). The purified OP induces new bone at less than 5 ng with half-maximal bone differentiation activity at about 20 ng/25 mg of matrix implant in a subcutaneous bone induction assay. The purified osteogenic protein is composed of disulfide-linked dimers that migrate on sodium dodecyl sulfate gels as a diffuse band with an apparent molecular weight of 30,000.

Risk factors for the spread of AIDS in rural Africa: evidence from a comparative seroepidemiological survey of AIDS, hepatitis B and syphilis in southwestern Uganda.

Before commencing rational control programmes for AIDS in Africa it is desirable to determine the relative importance of heterosexual and various non-sexual modes of transmission. We investigated this by comparing the seroepidemiologies of AIDS, hepatitis B and syphilis at two rural hospitals in southwest Uganda. During August 1986, 3% of 357 outpatients, reflecting the age and sex composition of the general population, were anti-HIV positive.

Characteristics of a simple measure of respiratory impedance.

The ratio of mouth pressure developed 0.1 sec after occlusion at end-expiration (P0.1) to average inspiratory flow rate (VT/TI) has been proposed as 'effective inspiratory impedance', Imeff.

Portable lung ventilators: the potential risk from bacterial colonisation.

Seven portable lung ventilators were investigated to assess the risk of bacterial colonization of the ventilator valve. One valve was deliberately contaminated with Serratia marcescens and the survival of organisms within the valve studied. Periods of colonization by Acinetobacter were found in all the hospital ventilators studied but none of those from the ambulance service.