61 research outputs found
Deterministic processes structure bacterial genetic communities across an urban landscape
Land-use change is predicted to act as a driver of zoonotic disease emergence through human exposure to novel microbial diversity, but evidence for the effects of environmental change on microbial communities in vertebrates is lacking. We sample wild birds at 99 wildlife-livestock-human interfaces across Nairobi, Kenya, and use whole genome sequencing to characterise bacterial genes known to be carried on mobile genetic elements (MGEs) within avian-borne Escherichia coli (n=241). By modelling the diversity of bacterial genes encoding virulence and antimicrobial resistance (AMR) against ecological and anthropogenic forms of urban environmental change, we demonstrate that communities of avian-borne bacterial genes are shaped by the assemblage of co-existing avian, livestock and human communities, and the habitat within which they exist. In showing that non-random processes structure bacterial genetic communities in urban wildlife, these findings suggest that it should be possible to forecast the effects of urban land-use change on microbial diversity
Risk factors for methamphetamine use in youth: a systematic review
<p>Abstract</p> <p>Background</p> <p>Methamphetamine (MA) is a potent stimulant that is readily available. Its effects are similar to cocaine, but the drug has a profile associated with increased acute and chronic toxicities. The objective of this systematic review was to identify and synthesize literature on risk factors that are associated with MA use among youth.</p> <p>More than 40 electronic databases, websites, and key journals/meeting abstracts were searched. We included studies that compared children and adolescents (≤ 18 years) who used MA to those who did not. One reviewer extracted the data and a second checked for completeness and accuracy. For discrete risk factors, odds ratios (OR) were calculated and when appropriate, a pooled OR with 95% confidence intervals (95% CI) was calculated. For continuous risk factors, mean difference and 95% CI were calculated and when appropriate, a weighted mean difference (WMD) and 95% CI was calculated. Results were presented separately by comparison group: low-risk (no previous drug abuse) and high-risk children (reported previous drug abuse or were recruited from a juvenile detention center).</p> <p>Results</p> <p>Twelve studies were included. Among low-risk youth, factors associated with MA use were: history of heroin/opiate use (OR = 29.3; 95% CI: 9.8–87.8), family history of drug use (OR = 4.7; 95% CI: 2.8–7.9), risky sexual behavior (OR = 2.79; 95% CI: 2.25, 3.46) and some psychiatric disorders. History of alcohol use and smoking were also significantly associated with MA use. Among high-risk youth, factors associated with MA use were: family history of crime (OR = 2.0; 95% CI: 1.2–3.3), family history of drug use (OR = 4.7; 95% CI: 2.8–7.9), family history of alcohol abuse (OR = 3.2; 95% CI: 1.8–5.6), and psychiatric treatment (OR = 6.8; 95% CI: 3.6–12.9). Female sex was also significantly associated with MA use.</p> <p>Conclusion</p> <p>Among low-risk youth, a history of engaging in a variety of risky behaviors was significantly associated with MA use. A history of a psychiatric disorder was a risk factor for MA for both low- and high-risk youth. Family environment was also associated with MA use. Many of the included studies were cross-sectional making it difficult to assess causation. Future research should utilize prospective study designs so that temporal relationships between risk factors and MA use can be established.</p
Epigenome Microarray Platform for Proteome-Wide Dissection of Chromatin-Signaling Networks
Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin
Crystal Structure of TDRD3 and Methyl-Arginine Binding Characterization of TDRD3, SMN and SPF30
SMN (Survival motor neuron protein) was characterized as a dimethyl-arginine binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3) and SPF30 (Splicing factor 30 kDa) were found to bind to various methyl-arginine proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be a transcriptional coactivator, and its transcriptional activity is dependent on its ability to bind arginine-methylated histone marks. In this study, we systematically characterized the binding specificity and affinity of the Tudor domains of these three proteins quantitatively. Our results show that TDRD3 preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a very promiscuous effector molecule, which recognizes different arginine containing sequence motifs and preferentially binds symmetrical dimethylated arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR motif sequences in our library. In addition, we also reported high-resolution crystal structures of the Tudor domain of TDRD3 in complex with two small molecules, which occupy the aromatic cage of TDRD3
PKCδ Sensitizes Neuroblastoma Cells to L-Buthionine-Sulfoximine and Etoposide Inducing Reactive Oxygen Species Overproduction and DNA Damage
Neuroblastoma is a type of pediatric cancer. The sensitivity of neuroblastoma (NB) cancer cells to chemotherapy and radiation is inhibited by the presence of antioxidants, such as glutathione (GSH), which is crucial in counteracting the endogenous production of reactive oxygen species (ROS). We have previously demonstrated that cells depleted of GSH undergo apoptosis via oxidative stress and Protein kinase C (PKC) δ activation. In the present study, we transfected PKCδ in NB cells resistant to oxidative death induced by L-buthionine-S,R-sulfoximine (BSO), a GSH-depleting agent. Cell responses, in terms of ROS production, apoptosis and DNA damage were evaluated. Moreover, PKCδ activation was monitored by analyzing the phosphorylation status of threonine 505 residue, carrying out PKC activity assay and investigating the subcellular localization of the kinase. The cell responses obtained in BSO-resistant cells were also compared with those obtained in BSO-sensitive cells subjected to the same experimental protocol. Our results demonstrate, for the first time, that PKCδ induces DNA oxidation and ROS overproduction leading to apoptosis of BSO-resistant NB cells and potentiates the cytotoxic effects induced by BSO in sensitive cells. Moreover, PKCδ overexpression enhances the sensitivity of NB cells to etoposide, a well-characterised drug, commonly used in neuroblastoma therapy. Altogether our data provide evidence of a pro-oxidant role of PKCδ that might be exploited to design new therapeutic strategies aimed at selective killing of cancer cells and overcoming drug resistance. However, it becomes evident that a more detailed understanding of ROS-mediated signaling in cancer cells is necessary for the development of redox-modulated therapeutic approaches
An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis
Long range physical cell-to-cell signalling via mitochondria inside membrane nanotubes: a hypothesis
Uniaxial Shear Strain as a Mechanism to Increase Spin Lifetime in Thin Film of a SOI-Based Silicon Spin FETs
Comparing two simplified questionnaire-based methods with 24-h recalls for estimating fortifiable wheat flour and oil consumption in Mandaluyong City, Philippines
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