Antibiotic resistance is increasingly widespread, largely due to human influence. Here, we explore the relationship between antibiotic resistance genes and the antimicrobial chemicals triclosan, ...triclocarban, and methyl-, ethyl-, propyl-, and butylparaben in the dust microbiome. Dust samples from a mixed-use athletic and educational facility were subjected to microbial and chemical analyses using a combination of 16S rRNA amplicon sequencing, shotgun metagenome sequencing, and liquid chromatography tandem mass spectrometry. The dust resistome was characterized by identifying antibiotic resistance genes annotated in the Comprehensive Antibiotic Resistance Database (CARD) from the metagenomes of each sample using the Short, Better Representative Extract Data set (ShortBRED). The three most highly abundant antibiotic resistance genes were tet(W), blaSRT-1, and erm(B). The complete dust resistome was then compared against the measured concentrations of antimicrobial chemicals, which for triclosan ranged from 0.5 to 1970 ng/g dust. We observed six significant positive associations between the concentration of an antimicrobial chemical and the relative abundance of an antibiotic resistance gene, including one between the ubiquitous antimicrobial triclosan and erm(X), a 23S rRNA methyltransferase implicated in resistance to several antibiotics. This study is the first to look for an association between antibiotic resistance genes and antimicrobial chemicals in dust.
While often obvious for macroscopic organisms, determining whether a microbe is dead or alive is fraught with complications. Fields such as microbial ecology, environmental health, and medical ...microbiology each determine how best to assess which members of the microbial community are alive, according to their respective scientific and/or regulatory needs. Many of these fields have gone from studying communities on a bulk level to the fine-scale resolution of microbial populations within consortia. For example, advances in nucleic acid sequencing technologies and downstream bioinformatic analyses have allowed for high-resolution insight into microbial community composition and metabolic potential, yet we know very little about whether such community DNA sequences represent viable microorganisms. In this review, we describe a number of techniques, from microscopy- to molecular-based, that have been used to test for viability (live/dead determination) and/or activity in various contexts, including newer techniques that are compatible with or complementary to downstream nucleic acid sequencing. We describe the compatibility of these viability assessments with high-throughput quantification techniques, including flow cytometry and quantitative PCR (qPCR). Although bacterial viability-linked community characterizations are now feasible in many environments and thus are the focus of this critical review, further methods development is needed for complex environmental samples and to more fully capture the diversity of microbes (e.g., eukaryotic microbes and viruses) and metabolic states (e.g., spores) of microbes in natural environments.
Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs) in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs ...because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2.
Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.
These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our laboratory and others reported that the stimulation of specific Toll-like receptors (TLRs) affects the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs). ...Toll-like receptors recognize "danger" signals, and their activation leads to profound cellular and systemic responses that mobilize innate and adaptive host immune cells. The danger signals that trigger TLRs are released following most tissue pathologies. Since danger signals recruit immune cells to sites of injury, we reasoned that hMSCs might be recruited in a similar way. Indeed, we found that hMSCs express several TLRs (e.g., TLR3 and TLR4), and that their migration, invasion, and secretion of immune modulating factors is drastically affected by specific TLR-agonist engagement. In particular, we noted diverse consequences on the hMSCs following stimulation of TLR3 when compared to TLR4 by our low-level, short-term TLR-priming protocol.
Here we extend our studies on the effect on immune modulation by specific TLR-priming of hMSCs, and based on our findings, propose a new paradigm for hMSCs that takes its cue from the monocyte literature. Specifically, that hMSCs can be polarized by downstream TLR signaling into two homogenously acting phenotypes we classify here as MSC1 and MSC2. This concept came from our observations that TLR4-primed hMSCs, or MSC1, mostly elaborate pro-inflammatory mediators, while TLR3-primed hMSCs, or MSC2, express mostly immunosuppressive ones. Additionally, allogeneic co-cultures of TLR-primed MSCs with peripheral blood mononuclear cells (PBMCs) predictably lead to suppressed T-lymphocyte activation following MSC2 co-culture, and permissive T-lymphocyte activation in co-culture with MSC1.
Our study provides an explanation to some of the conflicting reports on the net effect of TLR stimulation and its downstream consequences on the immune modulating properties of stem cells. We further suggest that MSC polarization provides a convenient way to render these heterogeneous preparations of cells more uniform while introducing a new facet to study, as well as provides an important aspect to consider for the improvement of current stem cell-based therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The amphibian fungal disease chytridiomycosis, which affects species across all continents, recently emerged as one of the greatest threats to biodiversity. Yet, many aspects of the basic biology and ...epidemiology of the pathogen, Batrachochytrium dendrobatidis (Bd), are still unknown, such as when and from where did Bd emerge and what is its true ecological niche? Here, we review the ecology and evolution of Bd in the Americas and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. Reevaluating the causes of the panzootic is timely given the wealth of data on Bd prevalence across hosts and communities and the recent discoveries suggesting co‐evolutionary potential of hosts and Bd. We generate a new species distribution model for Bd in the Americas based on over 30,000 records and suggest a novel future research agenda. Instead of focusing on pathogen “hot spots,” we need to identify pathogen “cold spots” so that we can better understand what limits the pathogen's distribution. Finally, we introduce the concept of “the Ghost of Epizootics Past” to discuss expected patterns in postepizootic host communities.
We review the ecology and evolution of amphibian fungal disease chytridiomycosis in the Americas, where it has recently emerged as one of the greatest threats to biodiversity and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. We generate a new species distribution model for Bd in the Americas based on over 30,000 records, which suggests emphasis needs to be placed on studying pathogen “cold spots” so that we can better understand what biotic and abiotic factors limit the pathogen's distribution.
Summary
What is known and objective
Breast cancer (BCa) and prostate cancer (PCa), both hormone‐dependent cancers, are the second leading cause of death in both women and men, respectively. Calcium ...channel blockers (CCBs) have been thought to increase the risk of cancer by inhibiting calcium signal‐mediated apoptosis, but the evidence for this association remains inconclusive. We have reviewed pertinent literature and pooled data to establish a consensus on the relationship of CCB use and the incidence of these two cancers.
Methods
PubMed was used to conduct a search for English articles from inception to April 2016. Relevant data including study design, number of total participants and CCB users, total cases of BCa and PCa, age (mean and/or range), follow‐up period and statistical outcomes were retrieved. Quality assessment was carried out using Newcastle Ottawa system, with the selection of high‐quality studies. Summary effects were obtained using random‐ and mixed‐effects models, followed by sensitivity analysis, and testing for publication bias.
Results and discussion
This meta‐analysis includes 11 relevant studies for BCa and 6 for PCa. The odds ratio (OR) association between BCa and CCB use was 1.14 (95%CI: 1.02, 1.27, P = .02). The OR association between PCa and CCB use was 1.12 (95%CI .94‐1.35, P = .21).
What is new and conclusion
Although a statistically significant association between CCB use and incidence of BCa does exist, the limitations of the individual studies restrict the clinical application of this relationship. Our meta‐regression model does newly identify a 9‐year latency period of CCB use and a significantly increased risk of BCa. No significant association exists between CCB use and the incidence of PCa. Our meta‐regression shows CCB may have a protective effect upon PCa incidence among older populations.
Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is the emerging infectious disease implicated in recent population declines and extinctions of amphibian species worldwide. ...Bd strains from regions of disease‐associated amphibian decline to date have all belonged to a single, hypervirulent clonal genotype (Bd‐GPL). However, earlier studies in the Atlantic Forest of southeastern Brazil detected a novel, putatively enzootic lineage (Bd‐Brazil), and indicated hybridization between Bd‐GPL and Bd‐Brazil. Here, we characterize the spatial distribution and population history of these sympatric lineages in the Brazilian Atlantic Forest. To investigate the genetic structure of Bd in this region, we collected and genotyped Bd strains along a 2400‐km transect of the Atlantic Forest. Bd‐Brazil genotypes were restricted to a narrow geographic range in the southern Atlantic Forest, while Bd‐GPL strains were widespread and largely geographically unstructured. Bd population genetics in this region support the hypothesis that the recently discovered Brazilian lineage is enzootic in the Atlantic Forest of Brazil and that Bd‐GPL is a more recently expanded invasive. We collected additional hybrid isolates that demonstrate the recurrence of hybridization between panzootic and enzootic lineages, thereby confirming the existence of a hybrid zone in the Serra da Graciosa mountain range of Paraná State. Our field observations suggest that Bd‐GPL may be more infective towards native Brazilian amphibians, and potentially more effective at dispersing across a fragmented landscape. We also provide further evidence of pathogen translocations mediated by the Brazilian ranaculture industry with implications for regulations and policies on global amphibian trade.
See also the Perspective by Ghosh and Fisher
We have developed a new prior-based source extraction tool, xid+, to carry out photometry in the Herschel SPIRE (Spectral and Photometric Imaging Receiver) maps at the positions of known sources. ...xid+ is developed using a probabilistic Bayesian framework that provides a natural framework in which to include prior information, and uses the Bayesian inference tool Stan to obtain the full posterior probability distribution on flux estimates. In this paper, we discuss the details of xid+ and demonstrate the basic capabilities and performance by running it on simulated SPIRE maps resembling the COSMOS field, and comparing to the current prior-based source extraction tool desphot. Not only we show that xid+ performs better on metrics such as flux accuracy and flux uncertainty accuracy, but we also illustrate how obtaining the posterior probability distribution can help overcome some of the issues inherent with maximum-likelihood-based source extraction routines. We run xid+ on the COSMOS SPIRE maps from Herschel Multi-Tiered Extragalactic Survey using a 24-...m catalogue as a positional prior, and a uniform flux prior ranging from 0.01 to 1000 mJy. We show the marginalized SPIRE colour-colour plot and marginalized contribution to the cosmic infrared background at the SPIRE wavelengths. xid+ is a core tool arising from the Herschel Extragalactic Legacy Project (HELP) and we discuss how additional work within HELP providing prior information on fluxes can and will be utilized. The software is available at https://github.com/H-E-L-P/XID_plus. We also provide the data product for COSMOS. We believe this is the first time that the full posterior probability of galaxy photometry has been provided as a data product. (ProQuest: ... denotes formulae/symbols omitted.)
Previous studies found an association between osteoarthritis (OA) and risk of cardiovascular disease (CVD) and therefore suggested intensive treatment of cardiovascular risk factors in OA patients. ...However, prospective population-based data is lacking.
To investigate the association between OA and CVD longitudinally in a general population and examine the role of disability in this association.
This study was embedded in the Rotterdam Study, a prospective population-based cohort study in Rotterdam, the Netherlands that started in 1989. At baseline 4648 persons aged ≥55, free of CVD were classified into those with and those without radiographic or clinical OA. HRs adjusted for traditional cardiovascular risk factors for developing CVD (a composite of fatal and non-fatal coronary heart disease and stroke) were calculated.
During a median follow-up of 14.4 years, 1230 cardiovascular events occurred, of which 101 were in participants with clinical OA. Presence of radiographic OA at baseline was not related to future CVD (HR 0.99, 95% CI 0.86 to 1.15), neither was presence of clinical OA (HR 1.09, 95% CI 0.88 to 1.34). However, persons with increasing disability were more likely to suffer a cardiovascular event compared with non-disabled persons (HR 1.26, 95% CI 1.12 to 1.42); this was independent of the presence of OA.
In this large population-based study, participants with OA were not at increased risk of CVD. The close relation between disability and osteoarthritis may explain previous findings. Further studies are required in order to clarify whether OA patients need more intensive treatment of their cardiovascular risk factors.
Aims
(i) To evaluate the role of pre‐existing weakness in working memory ability (WM) as a risk factor for early alcohol use as mediated by different forms of impulsivity and (ii) to assess the ...adverse effects of progressive alcohol use on variations in WM over time.
Design, setting and participants
A community sample of 358 adolescents 48% males, meanage(baseline) = 11.4 ± 0.87 years from a longitudinal cohort design, assessed annually over 4 consecutive years with less than 6% attrition.
Measurements
Repeated assessments were conducted for the following key variables: WM (based on performance on four separate tasks), frequency of alcohol use (AU) and three forms of impulsivity, namely sensation seeking (SS), acting without thinking (AWT) and delay discounting (DD). Latent growth curve modeling procedures were used to identify individual trajectories of change for all key variables.
Findings
Weakness in WM (at baseline) predicted significantly both concurrent alcohol use and increased frequency of use over the four waves (P < 0.05). This effect was entirely mediated by two forms of impulsivity, AWT and DD, both of which were characterized by underlying weakness in WM. No individual variation was observed in the slopes of WM, which suggests that individual variations in alcohol use were not associated with changes in WM in our early adolescent sample.
Conclusions
Early adolescent alcohol use may be a consequence of (pre‐existing) weaknesses in working memory (WM) rather than a cause of it. Efforts to reduce early alcohol use should consider the distinct roles of different impulsivity dimensions, in addition to WM, as potential targets of intervention.
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