Function of Metallothionein-3 in Neuronal Cells: Do Metal Ions Alter Expression Levels of MT3?

A study of factors proposed to affect metallothionein-3 (MT3) function was carried out to elucidate the opaque role MT3 plays in human metalloneurochemistry. Gene expression of Mt2 and Mt3 was examined in tissues extracted from the dentate gyrus of mouse brains and in human neuronal cell cultures. The whole-genome gene expression analysis identified significant variations in the mRNA levels of genes associated with zinc homeostasis, including Mt2 and Mt3. Mt3 was found to be the most differentially expressed gene in the identified groups, pointing to the existence of a factor, not yet identified, that differentially controls Mt3 expression. To examine the expression of the human metallothioneins in neurons, mRNA levels of MT3 and MT2 were compared in BE(2)C and SH-SY5Y cell cultures treated with lead, zinc, cobalt, and lithium. MT2 was highly upregulated by Zn2+ in both cell cultures, while MT3 was not affected, and no other metal had an effect on either MT2 or MT3

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids

Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species (n = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active

Human Papillomavirus Risk Perceptions Among Young Adult Sexual Minority Cisgender Women and Nonbinary Individuals Assigned Female at Birth

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148405/1/psrh12087_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148405/2/psrh12087.pd

Profiling Mechanisms of Alkane Hydroxylase Activity In Vivo Using the Diagnostic Substrate Norcarane

SummaryMechanistically informative chemical probes are used to characterize the activity of functional alkane hydroxylases in whole cells. Norcarane is a substrate used to reveal the lifetime of radical intermediates formed during alkane oxidation. Results from oxidations of this probe with organisms that contain the two most prevalent medium-chain-length alkane-oxidizing metalloenzymes, alkane ω-monooxygenase (AlkB) and cytochrome P450 (CYP), are reported. The results—radical lifetimes of 1–7 ns for AlkB and less than 100 ps for CYP—indicate that these two classes of enzymes are mechanistically distinguishable and that whole-cell mechanistic assays can identify the active hydroxylase. The oxidation of norcarane by several recently isolated strains (Hydrocarboniphaga effusa AP103, rJ4, and rJ5, whose alkane-oxidizing enzymes have not yet been identified) is also reported. Radical lifetimes of 1–3 ns are observed, consistent with these organisms containing an AlkB-like enzyme and inconsistent with their employing a CYP-like enzyme for growth on hydrocarbons

Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor

Genome-wide expression analyses of Campylobacter jejuni NCTC11168 reveals coordinate regulation of motility and virulence by flhA.

We examined two variants of the genome-sequenced strain, Campylobacter jejuni NCTC11168, which show marked differences in their virulence properties including colonization of poultry, invasion of Caco-2 cells, and motility. Transcript profiles obtained from whole genome DNA microarrays and proteome analyses demonstrated that these differences are reflected in late flagellar structural components and in virulence factors including those involved in flagellar glycosylation and cytolethal distending toxin production. We identified putative sigma(28) and sigma(54) promoters for many of the affected genes and found that greater differences in expression were observed for sigma(28)-controlled genes. Inactivation of the gene encoding sigma(28), fliA, resulted in an unexpected increase in transcripts with sigma(54) promoters, as well as decreased transcription of sigma(28)-regulated genes. This was unlike the transcription profile observed for the attenuated C. jejuni variant, suggesting that the reduced virulence of this organism was not entirely due to impaired function of sigma(28). However, inactivation of flhA, an important component of the flagellar export apparatus, resulted in expression patterns similar to that of the attenuated variant. These findings indicate that the flagellar regulatory system plays an important role in campylobacter pathogenesis and that flhA is a key element involved in the coordinate regulation of late flagellar genes and of virulence factors in C. jejuni

Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study

Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00-1.04 per 10g), waist-circumference (1.03; 1.01-1.05) and waist-to-hip ratio (1.04; 1.02-1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake

Conceptualising sustainability in UK urban Regeneration: a discursive Formation

Despite the wide usage and popular appeal of the concept of sustainability in UK policy, it does not appear to have challenged the status quo in urban regeneration because policy is not leading in its conceptualisation and therefore implementation. This paper investigates how sustainability has been conceptualised in a case-based research study of the regeneration of Eastside in Birmingham, UK, through policy and other documents, and finds that conceptualisations of sustainability are fundamentally limited. The conceptualisation of sustainability operating within urban regeneration schemes should powerfully shape how they make manifest (or do not) the principles of sustainable development. Documents guide, but people implement regeneration—and the disparate conceptualisations of stakeholders demonstrate even less coherence than policy. The actions towards achieving sustainability have become a policy ‘fix’ in Eastside: a necessary feature of urban policy discourse that is limited to solutions within market-based constraints

Exploratory use of fluorescent SmartProbes for the rapid detection of microbial isolates causing corneal ulcer

PURPOSE:To explore the use of optical SmartProbes for the rapid evaluation of corneal scrapes from patients with suspected microbial keratitis, as a clinical alternative to Gram stain. DESIGN:Experimental study with evaluation of a diagnostic technology. METHODS:Corneal scrapes were collected from 267 patients presenting with microbial keratitis at a referral cornea clinic in South India. Corneal scrapes were flooded with SmartProbes (BAC One or BAC Two) and evaluated by fluorescence microscopy (without the need for sample washing or further processing). The SmartProbe labelled samples were scored as bacteria/fungi/none (BAC One) or gram-negative bacteria/none (BAC Two) and compared to Gram stain results. RESULTS:Compared to Gram stain, BAC One demonstrated sensitivity and specificity of 80.0 and 87.5 percent respectively, positive and negative predictive values (PPV, NPV) of 93.8 and 65.1 percent, and an accuracy of 82.2. BAC Two demonstrated sensitivity and specificity of 93.3 and 84.8 percent respectively, a NPV of 99.2 percent and an accuracy of 85.6 percent. When the corresponding culture results were compared to the Gram stain result, the sensitivity and specificity were 73.4 and 70.7 percent, the PPV and NPVs were 86.5 and 51.0 percent, and an overall accuracy of 72.6. CONCLUSIONS:Fluorescent SmartProbes offer a comparative method to Gram stain for delineating gram-positive or gram-negative bacteria or fungi within corneal scrapes. We demonstrate equivalent or higher sensitivity, specificity, PPV and NPVs, and accuracy than culture to Gram stain. Our approach has scope for point-of-care clinical application to aid in the diagnosis of microbial keratitis

LakeEnsemblR: an R package that facilitates ensemble modelling of lakes

Model ensembles have several benefits compared to single-model applications but are not frequently used within the lake modelling community. Setting up and running multiple lake models can be challenging and time consuming, despite the many similarities between the existing models (forcing data, hypsograph, etc.). Here we present an R package, LakeEnsemblR, that facilitates running ensembles of five different vertical one-dimensional hydrodynamic lake models (FLake, GLM, GOTM, Simstrat, MyLake). The package requires input in a standardised format and a single configuration file. LakeEnsemblR formats these files to the input required by each model, and provides functions to run and calibrate the models. The outputs of the different models are compiled into a single file, and several post-processing operations are supported. LakeEnsemblR's workflow standardisation can simplify model benchmarking and uncertainty quantification, and improve collaborations between scientists. We showcase the successful application of LakeEnsemblR for two different lakes