Kainic Acid Induced Seizures and the GABA System in the Substantia Nigra

Author Institution: Department of Biological Sciences, Bowling Green State UniversityGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter implicated in the control of generalized seizures induced by various convulsants. A specific anatomical site of action, the substantia nigra (SN), has been shown to be involved in the GABA mediation of seizures. It was the objective of this study to investigate the GABA system in the SN and its response to seizures induced by the neuroexcitant kainic acid (KA). Since there have been conflicting reports of the effects of convulsants on GABA-related measures in some brain regions, with some reporting increases and others showing decreases, one purpose of this investigation was to examine the directionality of changes in GABA content of the SN, along with the magnitude of the effects of KA and the time course over which these effects were manifested. Rats were injected intraperitoneally with either 12.5 mg/kg KA or saline. GABA and protein contents of the SN were measured at 2, 16, 24 and 48 hrs subsequent to injection. The levels of GABA in the SN were found to increase in KA-injected animals over control levels for all time intervals except the 16 hr condition. These results are generally in conflict with those obtained by many researchers using the activity of the GABA synthetic enzyme glutamic acid decarboxylase (GAD) as a measure of GABA levels. It is suggested that GABA levels may actually increase in response to convulsants and serve to negatively feed back to its synthetic enzyme. Therefore, a decrease in GAD activity would not necessarily reflect a decrease in GABA levels. Future research directions include enzyme studies of both GAD and GABA transaminase and their regulation by products and substrates

Brood Provisioning And Nest Survival Of Ardea Herodias (Great Blue Heron) In Maine

From 1983–2009, the number of coastal breeding pairs of Ardea herodias (Great Blue Heron [GBHE]) in Maine declined by 64%, and the number of occupied islands on which these birds bred declined by 40%. The Maine Department of Inland Fisheries and Wildlife listed the GBHE as a species of special concern in 2007, and expanded its annual monitoring to include inland colonies in 2009. To assess regional demographic differences, we compared the relationship between brood provisioning and nest survival of GBHEs in 1 coastal and 1 inland colony. In terms of brood-provisioning within the 2 colonies, the inland colony had significantly greater rates for the first 2 weeks post-hatch, but the coastal colony had greater rates in subsequent weeks. These differences did not affect either nest fate (≥1 chick fledged) or daily nest survival at the inland or coastal colony. In both colonies, the maximum number of nestlings observed at a nest was positively correlated with the number that subsequently fledged. Daily nest survival was positively associated with an increasing number of nestlings, earlier hatch dates, and increased brood-provisioning rates for 1–2-week-old chicks. Our results suggest that the number of nestlings per nest can be used as a proxy for nest survival in GBHE colonies in the northeastern part of their range. Furthermore, because nest survival was influenced by brood-provisioning rates during the first 1–2 weeks post-hatch, our results suggest that the most sensitive time for disturbance of GBHEs in the northeastern part of their range may be earlier in the nesting stage than previously thought

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn\u27s Disease But Not Ulcerative Colitis.

BACKGROUND & AIMS: Patients with Crohn\u27s disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration. METHODS: We analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (\u3e2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes. RESULTS: Within 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P \u3c .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC. CONCLUSIONS: Patients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Rapid detection of an Ebola biomarker with optical microring resonators

Ebola virus (EBOV) is a highly infectious pathogen, with a case mortality rate as high as 89%. Rapid therapeutic treatments and supportive measures can drastically improve patient outcome; however, the symptoms of EBOV disease (EVD) lack specificity from other endemic diseases. Given the high mortality and significant symptom overlap, there is a critical need for sensitive, rapid diagnostics for EVD. Facile diagnosis of EVD remains a challenge. Here, we describe a rapid and sensitive diagnostic for EVD through microring resonator sensors in conjunction with a unique biomarker of EBOV infection, soluble glycoprotein (sGP). Microring resonator sensors detected sGP in under 40 min with a limit of detection (LOD) as low as 1.00 ng/mL in serum. Furthermore, we validated our assay with the detection of sGP in serum from EBOV-infected non-human primates. Our results demonstrate the utility of a high-sensitivity diagnostic platform for detection of sGP for diagnosis of EVD

Detection of biomarkers for filoviral infection with a silicon photonic resonator platform

This protocol describes the use of silicon photonic microring resonator sensors for detection of Ebola virus (EBOV) and Sudan virus (SUDV) soluble glycoprotein (sGP). This protocol encompasses biosensor functionalization of silicon microring resonator chips, detection of protein biomarkers in sera, preparing calibration standards for analytical validation, and quantification of the results from these experiments. This protocol is readily adaptable toward other analytes, including cytokines, chemokines, nucleic acids, and viruses. For complete details on the use and execution of this protocol, please refer to Qavi et al. (2022)

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

A synthesis of ENSO effects on drylands in Australia, North America and South America

Fundamentally, El Niño Southern Oscillation (ENSO) is a climatic and oceanographic phenomenon, but it has profound effects on terrestrial ecosystems. Although the ecological effects of ENSO are becoming increasingly known from a wide range of terrestrial ecosystems (Holmgren et al., 2001), their impacts have been more intensively studied in arid and semiarid systems. In this brief communication, we summarize the main conclusions of a recent symposium on the effects of ENSO in these ecosystems, which was convened as part of the First Alexander von Humboldt International Conference on the El Niño Phenomenon and its Global Impact, in Guayaquil, Ecuador, from 16–20 May 2005. Participants in the symposium shared results and perspectives from research conducted in North and South America and Australia, regions where the ecological effects of ENSO have been studied in depth. Although the reports covered a wide array of organisms and ecological systems (Fig. 1), a recurring theme was the strong increase in rainfall associated with ENSO events in dry ecosystems (during the El Niño phase of the oscillation in the Americas and the La Niña phase in Australia). Because inter-annual variability in precipitation is such a strong determinant of productivity in arid and semiarid ecosystems, increased ENSO rainfall is crucial for plant recruitment, productivity and diversity in these ecosystems. Several long-term studies show that this pulse in primary productivity causes a subsequent increase in herbivores, followed by an increase in carnivores, with consequences for changes in ecosystem structure and functioning that can be quite complex

Plague and Climate: Scales Matter

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations