Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome

Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O’Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033–2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS

A study of Sclerospora Graminicola (Sacc.) Schroet. on Setaria Viridis (L.) Beauv. and Zea Mays L.

Conidial sporulation of Sclerospora graminicola has been observed in the day time occurring naturally in the field and under artificial conditions in the laboratory. The period required for the development of mature conidia lies between 4 hours 35 minutes and 111/2 hours. The conditions which seem necessary for the production of conidia, whether during the day or night, are: a completely saturated atmosphere, turgid host leaves, a slight moisture film on the surface of the leaves and a temperature ranging between 8° and 27 °C. When flooded into a drop of water immediately after being discharged, conidia were found to germinate after 60 minutes. The best germination was obtained at 15°C., but the optimum was not definitely determined. Normal conidia measure 14-23 x 11-17µ. Sometimes larger conidia are produced (43 x 18.6µ) . The average length of conidiophores of Sclerospora graminicola was found to be 267.8µ while the individuals measured ranged from 214.5 to 375.3µ, a variation of 160.8µ. Spores were found to be forcefully discharged from the conidiophores thru a distance of 2.5 mm. vertically and 1.89 mm. horizontally. Setaria viridis, S. italica, Zea mays (May\u27s Golden popcorn) and Euchlaena mexicana were infected with Sclerospora graminicola when exposed to the conidia of the mildew. Oospores of Sclerospora graminicola were found to overwinter naturally in field soil under Iowa conditions. In one test, oospores which overwintered outdoors gave nearly twice as much infection on Setaria viridis and Zea Mays (Japanese Hulless popcorn) as did the oospores which were kept in the laboratory, Plants from five genera of Gramineae were found to be susceptible hosts to Sclerospora graminicola. These are: Euchlaena, Setaria, Holcus, Saccharum and Zea. Setaria viridis was found to be the most susceptible of all hosts and popcorn more susceptible than sweet corn and dent corn. Six days were found to be the usual period of incubation between the time oospores were placed on the seeds and that when conidial fruiting appeared on the leaves. Infection by oospores was obtained from the time the testa was broken until the emergence of the plumule above ground. Relative susceptibility of seedlings decreases with age. The processes connected with infection are more greatly favored by temperatures of 15° to 16°C. than by temperatures of 24° to 30°C. The germinating oospore is evidently unable to penetrate older leaf tissue. The viability of oospores was little affected by soaking in 2 percent copper sulfate solutions for 10 minutes, while similar treatment in 1 percent formaldehyde for 5 minutes proved fatal. The killing action of mercuric chloride 1-1000 was not so great as that of formaldehyde. Freshly collected oospores which were held in a dry condition at 77°C. for 1 hour later gave 52 percent infection on Setaria viridis, while wet spores lost their viability to a marked degree when held at 50°C. for a similar period. Sclerospora graminicola was studied in the field during the summers of 1925, 1926 and 1927. Infection was obtained on corn and teosinte planted in plots which had been artificially infested with oospores. Spontaneous conidial sporulation was found to be comparatively rare on corn in the field altho it was observed in 1926 and 1927 on young seedlings during periods of high humidity and cool temperatures. Infected plants were either killed outright or became stunted and unproductive. A few plants apparently outgrew the attack. In Iowa, Sclerospora graminicola has been observed only twice occurring naturally on corn in the field. Oospores of Sclerospora graminicola which had been held 30 months under dry conditions in the laboratory were found to be viable. Presoaking of oospores does not seem to affect the percentage of infection. Soil is not necessary as a medium for the germination of oospores

A fruit quality gene map of Prunus

<p>Abstract</p> <p>Background</p> <p><it>Prunus </it>fruit development, growth, ripening, and senescence includes major biochemical and sensory changes in texture, color, and flavor. The genetic dissection of these complex processes has important applications in crop improvement, to facilitate maximizing and maintaining stone fruit quality from production and processing through to marketing and consumption. Here we present an integrated fruit quality gene map of <it>Prunus </it>containing 133 genes putatively involved in the determination of fruit texture, pigmentation, flavor, and chilling injury resistance.</p> <p>Results</p> <p>A genetic linkage map of 211 markers was constructed for an intraspecific peach (<it>Prunus persica</it>) progeny population, Pop-DG, derived from a canning peach cultivar 'Dr. Davis' and a fresh market cultivar 'Georgia Belle'. The Pop-DG map covered 818 cM of the peach genome and included three morphological markers, 11 ripening candidate genes, 13 cold-responsive genes, 21 novel EST-SSRs from the ChillPeach database, 58 previously reported SSRs, 40 RAFs, 23 SRAPs, 14 IMAs, and 28 accessory markers from candidate gene amplification. The Pop-DG map was co-linear with the <it>Prunus </it>reference T × E map, with 39 SSR markers in common to align the maps. A further 158 markers were bin-mapped to the reference map: 59 ripening candidate genes, 50 cold-responsive genes, and 50 novel EST-SSRs from ChillPeach, with deduced locations in Pop-DG via comparative mapping. Several candidate genes and EST-SSRs co-located with previously reported major trait loci and quantitative trait loci for chilling injury symptoms in Pop-DG.</p> <p>Conclusion</p> <p>The candidate gene approach combined with bin-mapping and availability of a community-recognized reference genetic map provides an efficient means of locating genes of interest in a target genome. We highlight the co-localization of fruit quality candidate genes with previously reported fruit quality QTLs. The fruit quality gene map developed here is a valuable tool for dissecting the genetic architecture of fruit quality traits in <it>Prunus </it>crops.</p

Finite reduction and Morse index estimates for mechanical systems

A simple version of exact finite dimensional reduction for the variational setting of mechanical systems is presented. It is worked out by means of a thorough global version of the implicit function theorem for monotone operators. Moreover, the Hessian of the reduced function preserves all the relevant information of the original one, by Schur's complement, which spontaneously appears in this context. Finally, the results are straightforwardly extended to the case of a Dirichlet problem on a bounded domain.Comment: 13 pages; v2: minor changes, to appear in Nonlinear Differential Equations and Application

Serum kynurenic acid is reduced in affective psychosis

A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative Nmethyl- D-aspartate (NMDA) receptor agonist. In contrast, schizophrenia and psychosis are hypothesized to arise from increased metabolism of the NMDA receptor antagonist, kynurenic acid (KynA), leading to hypofunction of GABAergic interneurons, the disinhibition of pyramidal neurons and striatal hyperdopaminergia. Here we present results that challenge the model of excess KynA production in affective psychosis. After rigorous control of potential confounders and multiple testing we find significant reductions in serum KynA and/or KynA/QA in acutely ill inpatients with major depressive disorder (N = 35), bipolar disorder (N = 53) and schizoaffective disorder (N = 40) versus healthy controls (N = 92). No significant difference was found between acutely ill inpatients with schizophrenia (n = 21) and healthy controls. Further, a post hoc comparison of patients divided into the categories of non-psychotic affective disorder, affective psychosis and psychotic disorder (non-affective) showed that the greatest decrease in KynA was in the affective psychosis group relative to the other diagnostic groups. Our results are consistent with reports of elevations in proinflammatory cytokines in psychosis, and preclinical work showing that inflammation upregulates the enzyme, kynurenine mono-oxygenase (KMO), which converts kynurenine into 3-hydroxykynurenine and quinolinic acid

A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology

Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility

Use of an Outbred Rat Hepacivirus Challenge Model for Design and Evaluation of Efficacy of Different Immunization Strategies for Hepatitis C Virus

BACKGROUND AND AIMS: The lack of immunocompetent small animal models for hepatitis C virus (HCV) has greatly hindered the development of effective vaccines. Using rodent hepacivirus (RHV), a homolog of HCV that shares many characteristics of HCV infection, we report the development and application of an RHV outbred rat model for HCV vaccine development. APPROACH AND RESULTS: Simian adenovirus (ChAdOx1) encoding a genetic immune enhancer (truncated shark class II invariant chain) fused to the nonstructural (NS) proteins NS3-NS5B from RHV (ChAd-NS) was used to vaccinate Sprague-Dawley rats, resulting in high levels of cluster of differentiation 8-positive (CD8+ ) T-cell responses. Following RHV challenge (using 10 or 100 times the minimum infectious dose), 42% of vaccinated rats cleared infection within 6-8 weeks, while all mock vaccinated controls became infected with high-level viremia postchallenge. A single, 7-fold higher dose of ChAd-NS increased efficacy to 67%. Boosting with ChAd-NS or with a plasmid encoding the same NS3-NS5B antigens increased efficacy to 100% and 83%, respectively. A ChAdOx1 vector encoding structural antigens (ChAd-S) was also constructed. ChAd-S alone showed no efficacy. Strikingly, when combined with ChAd-NS, ChAD-S produced 83% efficacy. Protection was associated with a strong CD8+ interferon gamma-positive recall response against NS4. Next-generation sequencing of a putative RHV escape mutant in a vaccinated rat identified mutations in both identified immunodominant CD8+ T-cell epitopes. CONCLUSIONS: A simian adenovirus vector vaccine strategy is effective at inducing complete protective immunity in the rat RHV model. The RHV Sprague-Dawley rat challenge model enables comparative testing of vaccine platforms and antigens and identification of correlates of protection and thereby provides a small animal experimental framework to guide the development of an effective vaccine for HCV in humans

A 2022 Assessment of Food Security and Health Outcomes during the COVID-19 Pandemic

We conducted a Northern New England survey to understand the impacts of the COVID-19 pandemic on food security, food access, home food production, health behaviors, and health outcomes. The surveys were conducted in the spring of 2022 (April-May) with a total of 1,013 adults (598 in Maine and 415 in Vermont) responding to the survey. Key findings include:1. The prevalence of food insecurity remains similarly high to early points in the pandemic, likely driven by inflation and food prices, and long-term impacts from the pandemic. 2. The majority (62%) indicated the recent rise in food prices affected their food purchasing, this was significantly higher (90%) for food insecure respondents. 3. 1/3 of respondents utilized food assistance programs in the last 12 months. They reported difficulty traveling to food program offices to apply or recertify as a key challenge. 4. 2/3 of respondents engaged in some kind of home food production (HFP) and half of those did HFP activities for the first time or did existing HFP activities more in the last 12 months. 5. Nearly 1/3 reported weight gain during the COVID-19 pandemic. Food insecure respondents were significantly more likely to report weight gain. 6. Nearly 40% of food insecure respondents ate fewer fruits and vegetables and certain animal products in the last 12 months. These changes are significantly higher than for food secure respondents. 7. Half of the respondents faced a health care challenge in the last 12 months, with canceled appointments and trouble finding a timely appointment being the most commonly reported challenges. 8. More than 50% of respondents indicated anxiety and/or depression, with 17% of those with a diagnosis newly diagnosed in the last 12 months. 9. Compared to food secure respondents, food insecure respondents were significantly more likely to face a variety of health challenges in the last 12 months, including difficulty accessing healthcare, being diagnosed with anxiety and depression, stopping and skipping medications due to cost, and using habit-forming substances

Home Food Production and Food Security Since the COVID-19 Pandemic

We conducted a Northern New England survey to understand the initial and continued impacts of the COVID-19 pandemic on food security, food access, and home food production (HFP) (i.e. gardening, fishing, harvesting shellfish, foraging, hunting, trapping, raising animals for meat, dairy, or eggs, and food preservation such as canning, drying or freezing). The surveys were conducted in the Spring and Summer of 2021 (March – June). The survey was conducted in Maine (n = 562) and Vermont (n = 426). The cohort of respondents was representative of racial and ethnic identities of Vermont and Maine state populations. The data presented in this research brief were weighted to be representative of income in both states. Here, we summarize our findings related to changes in food security, food sourcing, and HFP before and since the COVID-19 pandemic. When data are referred to as “significant” it indicates a statistical significance at p\u3c 0.05

Optimal control problems with maximum functional

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76172/1/AIAA-20777-321.pd