The Political Dynamics of Mandatory State Constitutional Convention Referendums: Lessons from the 2000s Regarding Obstacles and Pathways to their Passage

State Constitutional Convention Referendum

Kynurenine pathway metabolism and the microbiota-gut-brain axis

It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside

Status of the Cerulean Warbler (\u3ci\u3eDendroica cerulea\u3c/i\u3e) in Nebraska

The Cerulean Warbler is a species of high conservation concern because of apparent long-term declines throughout its breeding range (Hamel 2000a, Hamel et al. 2004, Sauer et al. 2005) and threats to and reduction of breeding and wintering habitat (Hamel et al. 2004, Rick et al. 2004). Nebraska has traditionally been at the western periphery of the species\u27 breeding range, where it is restricted to mature woodlands in the Missouri River Valley (Sharpe et al. 2001, Mollhoff 2001). The Cerulean Warbler is a Tier I at-risk species under the Nebraska Natural Legacy Plan because it is a conservation priority (Schneider et al. 2005). In 2004, then Nebraska Game and Parks Commission Nongame Bird Program Manager John Dinan initiated a project to inventory the species\u27 breeding distribution in the state. Here, we review the species\u27 status in Nebraska by reference to previous reports and by summarizing results of the 2004 inventory. We also comment on habitat associations observed in Nebraska and consider possible explanations for the species\u27 limited distribution in the state

Status of the Cerulean Warbler (\u3ci\u3eDendroica cerulea\u3c/i\u3e) in Nebraska

The Cerulean Warbler is a species of high conservation concern because of apparent long-term declines throughout its breeding range (Hamel 2000a, Hamel et al. 2004, Sauer et al. 2005) and threats to and reduction of breeding and wintering habitat (Hamel et al. 2004, Rick et al. 2004). Nebraska has traditionally been at the western periphery of the species\u27 breeding range, where it is restricted to mature woodlands in the Missouri River Valley (Sharpe et al. 2001, Mollhoff 2001). The Cerulean Warbler is a Tier I at-risk species under the Nebraska Natural Legacy Plan because it is a conservation priority (Schneider et al. 2005). In 2004, then Nebraska Game and Parks Commission Nongame Bird Program Manager John Dinan initiated a project to inventory the species\u27 breeding distribution in the state. Here, we review the species\u27 status in Nebraska by reference to previous reports and by summarizing results of the 2004 inventory. We also comment on habitat associations observed in Nebraska and consider possible explanations for the species\u27 limited distribution in the state

A Review of Modern Bald Eagle (\u3ci\u3eHaliaeetus leucocephalus\u3c/i\u3e) Nesting Records and Breeding Status in Nebraska

The recovery of the Bald Eagle (Haliaeetus leucocephalus) in North America during the 20th century is a conservation success story. Once threatened with extinction, the species now is common throughout much of its range (Buehler 2000). Federal and state laws such as the Endangered Species Act (ESA; 16 U.S.C. 1531-1544) that were used to protect Bald Eagles and important habitats used by eagles are considered key actions that fostered the species\u27 recovery. In 2007, the Bald Eagle was formally removed from the federal list of threatened and endangered species (50 CFR Part 17). The following year, the Bald Eagle was removed from the Nebraska state list of threatened and endangered species. Bald Eagles have been a species of high conservation concern, and therefore a substantial amount of attention and resources has been directed toward monitoring Bald Eagle numbers over the past 50 years. Of particular interest were initial breeding records and subsequent increases in states where the species bred historically but was extirpated. Nebraska is one such state in which Bald Eagle breeding records have increased since protection

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required

Drunk bugs: chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice

The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N = 10) or air (Control, N = 9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p < 0.05) and beta (p < 0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p < 0.001) and significant reductions in genra Clostridium IV and XIVb (p < 0.001), Dorea (p < 0.01), and Coprococcus (p < 0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress

Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs)

When rhythms meet the blues: Circadian interactions with the microbiota-gut-brain axis

The microbiota-gut-brain axis encompasses a bidirectional mode of communication between the microorganisms residing in our gut, and our brain function and behavior. The composition of the gut microbiota is subject to diurnal variation and is entrained by host circadian rhythms. In turn, a diverse microbiota is essential for optimal regulation of host circadian pathways. Disruption of the cyclical nature of this microbe-host interaction profoundly influences disease pathology and severity. This review aims to summarize current knowledge on this bidirectional relationship. Indeed, the past few years have revealed promising data regarding the relationship between the microbiota-gut-brain axis and circadian rhythms and how they act in concert to influence disease, but further research needs to be done to examine how they coalesce to modulate severity of, and risk for, certain diseases. Moreover, there is a need for a greater understanding of the molecular mechanisms underlying the close relationship between circadian-microbiome-brain interactions