T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium.

The regulation of mucosal immune function is critical to host protection from enteric pathogens but is incompletely understood. The nervous system and the neurotransmitter acetylcholine play an integral part in host defense against enteric bacterial pathogens. Here we report that acetylcholine producing-T-cells, as a non-neuronal source of ACh, were recruited to the colon during infection with the mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong to one Th subset and were able to produce IFNγ, IL-17A and IL-22. To interrogate the possible protective effect of acetylcholine released from these cells during enteric infection, T-cells were rendered deficient in their ability to produce acetylcholine through a conditional gene knockout approach. Significantly increased C. rodentium burden was observed in the colon from conditional KO (cKO) compared to WT mice at 10 days post-infection. This increased bacterial burden in cKO mice was associated with increased expression of the cytokines IL-1β, IL-6, and TNFα, but without significant changes in T-cell and ILC associated IL-17A, IL-22, and IFNγ, or epithelial expression of antimicrobial peptides, compared to WT mice. Despite the increased expression of pro-inflammatory cytokines during C. rodentium infection, inducible nitric oxide synthase (Nos2) expression was significantly reduced in intestinal epithelial cells of ChAT T-cell cKO mice 10 days post-infection. Additionally, a cholinergic agonist enhanced IFNγ-induced Nos2 expression in intestinal epithelial cell in vitro. These findings demonstrated that acetylcholine, produced by specialized T-cells that are recruited during C. rodentium infection, are a key mediator in host-microbe interactions and mucosal defenses

Setting scientific names at all taxonomic ranks in italics facilitates their quick recognition in scientific papers

It is common practice in scientific journals to print genus and species names in italics. This is not only historical as species names were traditionally derived from Greek or Latin. Importantly, it also facilitates the rapid recognition of genus and species names when skimming through manuscripts. However, names above the genus level are not always italicized, except in some journals which have adopted this practice for all scientific names. Since scientific names treated under the various Codes of nomenclature are without exception treated as Latin, there is no reason why names above genus level should be handled differently, particularly as higher taxon names are becoming increasingly relevant in systematic and evolutionary studies and their italicization would aid the unambiguous recognition of formal scientific names distinguishing them from colloquial names. Several leading mycological and botanical journals have already adopted italics for names of all taxa regardless of rank over recent decades, as is the practice in the International Code of Nomenclature for algae, fungi, and plants, and we hereby recommend that this practice be taken up broadly in scientific journals and textbooks

Mouse genome-wide association studies and systems genetics uncover the genetic architecture associated with hepatic pharmacokinetic and pharmacodynamic properties of a constrained ethyl antisense oligonucleotide targeting Malat1

Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 (Vamp3) were identified by ciseQTL analysis. HMDP strains with lower Stab2 expression and Stab2 KO mice displayed significantly lower PK than strains with higher Stab2 expression and the wild type (WT) animals respectively, confirming the role of Stab2 in regulating hepatic Malat1 ASO uptake. GWA examining ASO efficacy uncovered three loci associated with Malat1 potency: Small Subunit Processome Component (Utp11l) on chromosome 4, Rho associated coiled-coil containing protein kinase 2 (Rock2) and Aci-reductone dioxygenase (Adi1) on chromosome 12. Our results demonstrate the utility of mouse GWAS using the HMDP in detecting genes capable of impacting the uptake of ASOs, and identifies genes critical for the activity of ASOs in vivo

Assessing gender mainstreaming in the education sector: depoliticised technique or a step towards women's rights and gender equality?

In 1995 the Beijing Conference on Women identified gender mainstreaming as a key area for action. Policies to effect gender mainstreaming have since been widely adopted. This special issue of Compare looks at research on how gender mainstreaming has been used in government education departments, schools, higher education institutions, international agencies and NGOs .1 In this introduction we first provide a brief history of the emergence of gender mainstreaming and review changing definitions of the term. In the process we outline some policy initiatives that have attempted to mainstream gender and consider some difficulties with putting ideas into practice, particularly the tensions between a technical and transformative interpretations . Much of the literature about experiences with gender mainstreaming tends to look at organizational processes and not any specificities of a particular social sector. However, in our second section, we are concerned to explore whether institutional forms and particular actions associated with education give gender mainstreaming in education sites some distinctive features. In our last section we consider some of the debates about global and local negotiations in discussions of gender policy and education and the light this throws on gender mainstreaming. In so doing, we place the articles that follow in relation to contestations over ownership, political economy, the form and content of education practice and the social complexity of gender equality

Impacts of Climate Change on Multiple Use Management of Bureau of Land Management Land in the Intermountain West, USA

Although natural resource managers are concerned about climate change, many are unable to adequately incorporate climate change science into their adaptation strategies or management plans, and are not always aware of or do not employ the most current scientific knowledge. One of the most prominent natural resource management agencies in the United States is the Bureau of Land Management (BLM), which is tasked with managing over 248 million acres (\u3e1 million km2) of public lands for multiple, often conflicting, uses. Climate change will affect the sustainability of many of these land uses and could further increase conflicts between them. As such, the purpose of our study was to determine the extent to which climate change will affect public land uses, and whether the BLM is managing for such predicted effects. To do so, we first conducted a systematic review of peer-reviewed literature that discussed potential impacts of climate change on the multiple land uses the BLM manages in the Intermountain West, USA, and then expanded these results with a synthesis of projected vegetation changes. Finally, we conducted a content analysis of BLM Resource Management Plans in order to determine how climate change is explicitly addressed by BLM managers, and whether such plans reflect changes predicted by the scientific literature. We found that active resource use generally threatens intrinsic values such as conservation and ecosystem services on BLM land, and climate change is expected to exacerbate these threats in numerous ways. Additionally, our synthesis of vegetation modeling suggests substantial changes in vegetation due to climate change. However, BLM plans rarely referred to climate change explicitly and did not reflect the results of the literature review or vegetation model synthesis. Our results suggest there is a disconnect between management of BLM lands and the best available science on climate change. We recommend that the BLM actively integrates such research into on-the-ground management plans and activities, and that researchers studying the effects of climate change make a more robust effort to understand the practices and policies of public land management in order to effectively communicate the management significance of their findings

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners

Cranial Ultrasound Lesions in the NICU Predict Cerebral Palsy at Age 2 Years in Children Born at Extremely Low Gestational Age

Our prospective cohort study of extremely low gestational age newborns evaluated the association of neonatal head ultrasound abnormalities with cerebral palsy at age 2 years. Cranial ultrasounds in 1053 infants were read with respect to intraventricular hemorrhage, ventriculomegaly, and echolucency, by multiple sonologists. Standardized neurological examinations classified cerebral palsy, and functional impairment was assessed. Forty-four percent with ventriculomegaly and 52% with echolucency developed cerebral palsy. Compared with no ultrasound abnormalities, children with echolucency were 24 times more likely to have quadriparesis and 29 times more likely to have hemiparesis. Children with ventriculomegaly were 17 times more likely to have quadriparesis or hemiparesis. Forty-three percent of children with cerebral palsy had normal head ultrasound. Focal white matter damage (echolucency) and diffuse damage (late ventriculomegaly) are associated with a high probability of cerebral palsy, especially quadriparesis. Nearly half the cerebral palsy identified at 2 years is not preceded by a neonatal brain ultrasound abnormality. Originally published Journal of Child Neurology, Vol. 24, No. 1, Jan 200

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here