Prospectus, July 17, 2002

https://spark.parkland.edu/prospectus_2002/1018/thumbnail.jp

Occurrence of Alkaloids in Grass Seeds Symbiotic With Vertically-Transmitted \u3cem\u3eEpichloë\u3c/em\u3e Fungal Endophytes and Its Relationship With Antioxidants

Host organisms can acquire new functional traits through symbiosis. Seed-transmitted Epichloë fungal endophytes are known to protect host plants against herbivores and increase tolerance to abiotic stresses by alkaloids and antioxidants, respectively (currencies of mutualism). Whereas, alkaloids are fungal products with demonstrated effects at plant vegetative stage, few studies have focused on alkaloids in seeds. We assessed the occurrence of fungal alkaloids and determined their concentrations in seeds of two host grasses, Festuca rubra and Lolium multiflorum. Then, we sought for a relationship with the antioxidants tocochromanols and glutathione, which are involved in the control of oxidative stress. Different alkaloids were detected depending on the species and plant genotype. Most notably, loline alkaloids were not detected in F. rubra seeds, whereas ergovaline and peramine were absent in L. multiflorum. In F. rubra, ergovaline concentration was dependent on the maternal line in interaction with the production year, diminishing in seeds after 1 year of storage. The exposure of L. multiflorum plants to ozone had no effect on the seed concentration of lolines. There was a significant positive relationship between the concentrations of ergovaline and tocochromanols in both species, and between ergovaline concentration and EGSSG/2GSH (glutathione half-cell reduction potential) in RAB maternal line of F. rubra. These results suggest that alkaloid and antioxidants have a close association in seeds of host grasses, and that the alkaloid bioactivity could be related with the antioxidant capacity to control stress. This has important implications for the ecology of partner species, thus supporting its consideration for further research

Metformin Blunts Muscle Hypertrophy in Response to Progressive Resistance Exercise Training in Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The MASTERS Trial

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p \u3c .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228

Examination of ataxin-3 (atx-3) aggregation by structural mass spectrometry techniques: A rationale for expedited aggregation upon polyglutamine (polyQ) expansion

Expansion of polyglutamine stretches leads to the formation of polyglutamine-containing neuronal aggregates and neuronal death in nine diseases for which there currently are no treatments or cures. This is largely due to a lack in understanding of the mechanisms by which expanded polyglutamine regions contribute to aggregation and disease. To complicate matters further, several of the polyglutamine-disease related proteins, including ataxin-3, have a multistage aggregation mechanism in which flanking domain self-assembly precedes polyglutamine aggregation yet is influenced by polyglutamine expansion. How polyglutamine expansion influences flanking domain aggregation is poorly understood. Here, we use a combination of mass spectrometry and biophysical approaches to investigate this issue for ataxin-3. We show that the conformational dynamics of the flanking Josephin domain in ataxin-3 with an expanded polyglutamine tract are altered in comparison to those exhibited by its nonexpanded counterpart, specifically within the aggregation-prone region of the Josephin domain (amino acid residues 73-96). Expansion thus exposes this region more frequently in ataxin-3 containing an expanded polyglutamine tract, providing a molecular explanation of why aggregation is accelerated upon polyglutamine expansion. Here, harnessing the power of ion mobility spectrometry-mass spectrometry, oligomeric species formed during aggregation are characterized and a model for oligomer growth proposed. The results suggest that a conformational change occurs at the dimer level that initiates self-assembly. New insights into ataxin-3 fibril architecture are also described, revealing the region of the Josephin domain involved in protofibril formation and demonstrating that polyglutamine aggregation proceeds as a distinct second step after protofibril formation without requiring structural rearrangement of the protofibril core. Overall, the results enable the effect of polyglutamine expansion on every stage of ataxin-3 self-assembly, from monomer through to fibril, to be described and a rationale for expedited aggregation upon polyglutamine expansion to be provided

Occurrence of Alkaloids in Grass Seeds Symbiotic With Vertically-Transmitted Epichloë Fungal Endophytes and Its Relationship With Antioxidants

Host organisms can acquire new functional traits through symbiosis. Seed-transmitted Epichloë fungal endophytes are known to protect host plants against herbivores and increase tolerance to abiotic stresses by alkaloids and antioxidants, respectively (currencies of mutualism). Whereas, alkaloids are fungal products with demonstrated effects at plant vegetative stage, few studies have focused on alkaloids in seeds. We assessed the occurrence of fungal alkaloids and determined their concentrations in seeds of two host grasses, Festuca rubra and Lolium multiflorum. Then, we sought for a relationship with the antioxidants tocochromanols and glutathione, which are involved in the control of oxidative stress. Different alkaloids were detected depending on the species and plant genotype. Most notably, loline alkaloids were not detected in F. rubra seeds, whereas ergovaline and peramine were absent in L. multiflorum. In F. rubra, ergovaline concentration was dependent on the maternal line in interaction with the production year, diminishing in seeds after 1 year of storage. The exposure of L. multiflorum plants to ozone had no effect on the seed concentration of lolines. There was a significant positive relationship between the concentrations of ergovaline and tocochromanols in both species, and between ergovaline concentration and EGSSG/2GSH (glutathione half-cell reduction potential) in RAB maternal line of F. rubra. These results suggest that alkaloid and antioxidants have a close association in seeds of host grasses, and that the alkaloid bioactivity could be related with the antioxidant capacity to control stress. This has important implications for the ecology of partner species, thus supporting its consideration for further research

A volumetric technique for fossil body mass estimation applied to Australopithecus afarensis

Fossil body mass estimation is a well established practice within the field of physical anthropology. Previous studies have relied upon traditional allometric approaches, in which the relationship between one/several skeletal dimensions and body mass in a range of modern taxa is used in a predictive capacity. The lack of relatively complete skeletons has thus far limited the potential application of alternative mass estimation techniques, such as volumetric reconstruction, to fossil hominins. Yet across vertebrate paleontology more broadly, novel volumetric approaches are resulting in predicted values for fossil body mass very different to those estimated by traditional allometry. Here we present a new digital reconstruction of Australopithecus afarensis (A.L. 288-1; ‘Lucy’) and a convex hull-based volumetric estimate of body mass. The technique relies upon identifying a predictable relationship between the ‘shrink-wrapped’ volume of the skeleton and known body mass in a range of modern taxa, and subsequent application to an articulated model of the fossil taxa of interest. Our calibration dataset comprises whole body computed tomography (CT) scans of 15 species of modern primate. The resulting predictive model is characterized by a high correlation coefficient (r2 = 0.988) and a percentage standard error of 20%, and performs well when applied to modern individuals of known body mass. Application of the convex hull technique to A. afarensis results in a relatively low body mass estimate of 20.4 kg (95% prediction interval 13.5–30.9 kg). A sensitivity analysis on the articulation of the chest region highlights the sensitivity of our approach to the reconstruction of the trunk, and the incomplete nature of the preserved ribcage may explain the low values for predicted body mass here. We suggest that the heaviest of previous estimates would require the thorax to be expanded to an unlikely extent, yet this can only be properly tested when more complete fossils are available

Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Determinants of willingness to receive healthy lifestyle advice in the context of cancer screening

Background: Providing lifestyle advice at cancer screening may help reduce the cancer burden attributable to health-related behaviour. We examined determinants of willingness to receive advice about several behavioural cancer risk factors. Methods: A population-based sample of English adults eligible for cancer screening (n = 1221) completed items on willingness to receive lifestyle advice. Sociodemographic, psychological (risk perceptions, cancer risk factor awareness) and behavioural factors were used to predict interest in advice about diet, weight, physical activity, smoking and alcohol consumption. Results: Two thirds (62–67%) reported interest in advice about diet, weight, and physical activity; 17% were willing to receive advice about smoking, and 32% about alcohol consumption. Willingness to receive advice was higher in those not adhering to guidelines for weight, physical activity, smoking and alcohol consumption (all p < 0.01). Non-White ethnicity was associated with interest in advice about diet, physical activity and smoking (all p < 0.01). Willingness to receive advice about diet, weight, physical activity and alcohol consumption increased with greater recognition of cancer risk factors (all p < 0.01). Conclusions: Willingness to receive lifestyle advice at cancer screening was high, suggesting this context may provide an opportunity to support behaviour change. Increasing awareness of cancer risk factors may facilitate interest in lifestyle advice

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele