Modelling Child Poverty and Wellbeing the Treasury’s TAWA microsimulation model

Large tax–transfer microsimulation models can play a key role in guiding tax–transfer analysis and reform. This article discusses the Treasury’s microsimulation model of the tax–transfer system (the Tax and Welfare Analysis (TAWA) model), including how it is used and the standard outputs it produces. The article also considers whether these standard outputs continue to be fit for purpose. This includes a discussion of different ways of estimating poverty impacts, the role reporting should give to financial incentives to work, and the opportunities provided by improved data. This final point is particularly important for understanding take-up and the prospect for extending the model to cover non-financial measures

Inflammation in Parkinson's disease: causes and consequences

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease (AD) with a prevalence of 0.5-1 % among persons older than 65 years of age (Toulouse & Sullivan, 2008). The incidence increases to 2.6 % in persons aged 85 and older, and has a mean age of onset of 55 years. Statistics released in 1990 from

Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators

Adolescence is a critical period for brain maturation. Deciphering how disturbances to the central nervous system at this time affect structure, function and behavioural outputs is important to better understand any long-lasting effects. Hippocampal neurogenesis occurs during development and continues throughout life. In adulthood, integration of these new cells into the hippocampus is important for emotional behaviour, cognitive function and neural plasticity. During the adolescent period, maturation of the hippocampus and heightened levels of hippocampal neurogenesis are observed, making alterations to neurogenesis at this time particularly consequential. As stress negatively affects hippocampal neurogenesis, and adolescence is a particularly stressful time of life, it is important to investigate the impact of stressor exposure at this time on hippocampal neurogenesis and cognitive function. Adolescence may represent not only a time for which stress can have long-lasting effects, but is also a critical period during which interventions, such as exercise and diet, could ameliorate stress-induced changes to hippocampal function. In addition, intervention at this time may also promote life-long behavioural changes that would aid in fostering increased hippocampal neurogenesis and cognitive function. This review addresses both the acute and long-term stress-induced alterations to hippocampal neurogenesis and cognition during the adolescent period, as well as changes to the stress response and pubertal hormones at this time which may result in differential effects than are observed in adulthood. We hypothesise that adolescence may represent an optimal time for healthy lifestyle changes to have a positive and long-lasting impact on hippocampal neurogenesis, and to protect against stress-induced deficits. We conclude that future research into the mechanisms underlying the susceptibility of the adolescent hippocampus to stress, exercise and diet and the consequent effect on cognition may provide insight into why adolescence may be a vital period for correct conditioning of future hippocampal function

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

Idiopathic Parkinson’s disease (PD) represents a complex interaction between the inherent vulnerability of the nigrostriatal dopaminergic system, a possible genetic predisposition, and exposure to environmental toxins including inflammatory triggers. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of PD. Activation of microglia and increased levels of pro-inflammatory mediators such as TNF-alpha,IL-1beta and IL-6, reactive oxygen species and eicosanoids has been reported after post mortem analysis of the substantia nigra from PD patients and in animal models of PD. It is hypothesised that chronically activated microglia secrete high levels of pro-inflammatory mediators which damage neurons and further activate microglia, resulting in a feed forward cycle promoting further inflammation and neurodegeneration. Moreover, nigrostriatal dopaminergic neurons are more vulnerable to pro-inflammatory and oxidative mediators than other cell types because of their low intracellular glutathione concentration. Systemic inflammation has also been suggested to contribute to neurodegeneration in PD, as lymphocyte infiltration has been observed in brains of PD patients and in animal models of PD, substantiating the current theory of a fundamental role of inflammation in neurodegeneration. We will examine the current evidence in the literature which offers insight into the premise that both central and systemic inflammation may contribute to neurodegeneration in PD. We will discuss the emerging possibility of the use of diagnostic tools such as imaging technologies for PD patients. Finally, we will present the immunomodulatory therapeutic strategies that are now under investigation and in clinical trials as potential neuroprotective drugs for PD

Escherichia coli, Salmonella, and Mycobacterium avium subsp. paratuberculosis in Wild European Starlings at a Kansas Cattle Feedlot

The prevalence of Escherichia coli, Salmonella spp., and Mycobacterium avium subsp.paratuberculosis isolated from the feces of wild European starlings (Sturnus vulgaris) humanely trapped at a feedlot in central Kansas was assessed. All E. coli and Salmonellaisolates recovered were tested for antimicrobial susceptibility using National Antimicrobial Resistance Monitoring System panels and the E. coli isolates were classified as to their content of genes associated with pathogenic E. coli of birds and cattle, including cvaC, iroN2, ompTp, hlyF2, eitC, iss, iutA, ireA, papC, stxI, stxII, sta, K99, F41, and eae.Escherichia coli O157:H7 and Mycobacterium avium subsp. paratuberculosis were not detected and Salmonella was isolated from only three samples, two of which displayed antimicrobial resistance. Approximately half of the E. coli isolates were resistant to antimicrobial agents with 96% showing resistance to tetracycline. Only one isolate was positive for a single gene associated with bovine pathogenic E. coli. An interesting finding of this study was that 5% of the E. coli isolates tested met the criteria established for identification as avian pathogenic E. coli (APEC). Thus these findings suggest that starlings are not a significant source of Salmonella spp., Mycobacterium avium subsp.paratuberculosis, E. coli O157, or other shiga toxin–producing E. coli in this feedlot. However, they may have the potential to spread APEC, an important pathogen of poultry and a potential pathogen to human beings

tkt1, located on a novel pathogenicity island, is prevalent in avian and human extraintestinal pathogenic Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Extraintestinal pathogenic <it>Escherichia coli </it>are important pathogens of human and animal hosts. Some human and avian extraintestinal pathogenic <it>E. coli </it>are indistinguishable on the basis of diseases caused, multilocus sequence and phylogenetic typing, carriage of large virulence plasmids and traits known to be associated with extraintestinal pathogenic <it>E. coli </it>virulence.</p> <p>Results</p> <p>The gene <it>tkt1 </it>identified by a previous signature-tagged transposon mutagenesis study, was found on a 16-kb genomic island of avian pathogenic <it>Escherichia coli </it>(APEC) O1, the first pathogenic <it>Escherichia coli </it>strain whose genome has been completely sequenced. <it>tkt1 </it>was present in 39.6% (38/96) of pathogenic <it>Escherichia coli </it>strains, while only 6.25% (3/48) of <it>E. coli </it>from the feces of apparently healthy chickens was positive. Further, <it>tkt1 </it>was predominantly present in extraintestinal pathogenic <it>E. coli </it>belonging to the B2 phylogenetic group, as compared to extraintestinal pathogenic <it>E. coli </it>of other phylogenetic groups. The <it>tkt1</it>-containing genomic island is inserted between the <it>metE </it>and <it>ysgA </it>genes of the <it>E. coli </it>K12 genome. Among different extraintestinal pathogenic <it>E. coli </it>of the B2 phylogenetic group, 61.7% of pathogenic <it>Escherichia coli</it>, 80.6% of human uropathogenic <it>E.coli </it>and 94.1% of human neonatal meningitis-causing <it>E. coli</it>, respectively, harbor a complete copy of this island; whereas, only a few avian fecal <it>E. coli </it>strains contained the complete island. Functional analysis showed that Tkt1 confers very little transketolase activity but is involved in peptide nitrogen metabolism.</p> <p>Conclusion</p> <p>These results suggest <it>tkt1 </it>and its corresponding genomic island are frequently associated with avian and human ExPEC and are involved in bipeptide metabolism.</p

Complete Genome Sequence of the Avian Pathogenic Escherichia coli Strain APEC O78

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), is a significant disease, causing extensive animal and financial losses globally. Because of the significance of this disease, more knowledge is needed regarding APEC\u27s mechanisms of virulence. Here, we present the fully closed genome sequence of a typical avian pathogenic E. coli strain belonging to the serogroup O78

Genotypic and Phenotypic Traits That Distinguish Neonatal Meningitis-Associated Escherichia coli from Fecal E. coli Isolates of Healthy Human Hosts

Neonatal meningitis Escherichia coli (NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecal E. coli isolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number of E. coli strains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenic E. coli genomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype

Comparison of Extraintestinal Pathogenic Escherichia coli Strains from Human and Avian Sources Reveals a Mixed Subset Representing Potential Zoonotic Pathogens

Since extraintestinal pathogenic Escherichia coli (ExPEC) strains from human and avian hosts encounter similar challenges in establishing infection in extraintestinal locations, they may share similar contents of virulence genes and capacities to cause disease. In the present study, 1,074 ExPEC isolates were classified by phylogenetic group and possession of 67 other traits, including virulence-associated genes and plasmid replicon types. These ExPEC isolates included 452 avian pathogenic E. coli strains from avian colibacillosis, 91 neonatal meningitis E. coli (NMEC) strains causing human neonatal meningitis, and 531 uropathogenic E. coli strains from human urinary tract infections. Cluster analysis of the data revealed that most members of each subpathotype represent a genetically distinct group and have distinguishing characteristics. However, a genotyping cluster containing 108 ExPEC isolates was identified, heavily mixed with regard to subpathotype, in which there was substantial trait overlap. Many of the isolates within this cluster belonged to the O1, O2, or O18 serogroup. Also, 58% belonged to the ST95 multilocus sequence typing group, and over 90% of them were assigned to the B2 phylogenetic group typical of human ExPEC strains. This cluster contained strains with a high number of both chromosome- and plasmid-associated ExPEC genes. Further characterization of this ExPEC subset with zoonotic potential urges future studies exploring the potential for the transmission of certain ExPEC strains between humans and animals. Also, the widespread occurrence of plasmids among NMEC strains and members of the mixed cluster suggests that plasmid-mediated virulence in these pathotypes warrants further attention

A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli\u27s Ability to Exploit Abundant Host Metabolites

wo-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilizationregulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes,c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenicE. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract