298 research outputs found

    Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

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    Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine ÎČ-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD

    Pannexin 1 drives efficient epithelial repair after tissue injury

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    Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2, both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury

    Beyond ''women's traits'': exploring how gender, social difference and household characteristics influence trait preferences

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    Open Access Journal; Published online: 14 Dec 2021Demand-led breeding strategies are gaining importance in public sector breeding globally. While borrowing approaches from the private sector, public sector programs remain mainly focused on food security and social impact related outcomes. This necessitates information on specific user groups and their preferences to build targeted customer and product profiles for informed breeding decisions. A variety of studies have identified gendered trait preferences, but do not systematically analyze differences related to or interactions of gender with other social dimensions, household characteristics, and geographic factors. This study integrates 1000minds survey trait trade-off analysis with the Rural Household Multi-Indicator Survey to study cassava trait preferences in Nigeria related to a major food product, gari. Results build on earlier research demonstrating that women prioritize food product quality traits while men prioritize agronomic traits. We show that food product quality traits are more important for members from food insecure households and gender differences between men and women increase among the food insecure. Furthermore, respondents from poorer households prioritize traits similar to respondents in non-poor households but there are notable trait differences between men and women in poor households. Women in female headed household prioritized quality traits more than women living with a spouse. Important regional differences in trait preferences were also observed. In the South East region, where household use of cassava is important, and connection to larger markets is less developed, quality traits and in ground storability were prioritized more than in other states. These results reinforce the importance of recognizing social difference and the heterogeneity among men and women, and how individual and household characteristics interact to reveal trait preference variability. This information can inform trait prioritization and guide development of breeding products that have higher social impact, which may ultimately serve the more vulnerable and align with development goals

    Cassava trait preferences of men and women farmers in Nigeria: implications for breeding

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    Nigeria is the world’s largest cassava producer, hosting a diverse array of cassava farmers and processors. Cassava breeding programs prioritize “common denominator” traits in setting breeding agendas, to impact the largest possible number of people through improved varieties. This approach has been successful, but cassava adoption rates are less than expected, with room for improvement by integrating traits in demand by farmers and processors. This paper aims to inform breeding priority setting, by examining trait and varietal preferences of men and women cassava farmer/processors. Men and women in eight communities in Southwest and Southeast Nigeria were consulted using mixed methods. Women and men had significantly different patterns of cassava use in the Southwest. Fifty-five variety names were recorded from the communities demonstrating high genetic diversity maintained by growers, especially in the Southeast. High yield, early maturity, and root size were most important traits across both regions, while traits women and men preferred followed gender roles: women prioritized product quality/cooking traits, while men placed higher priority on agronomic traits. Trait preference patterns differed significantly between the Southeast and Southwest, and showed differentiation based on gender. Patterns of access to stem sources were determined more by region and religion than gender

    Stressors and resilience within the cassava value chain in Nigeria: preferred cassava variety traits and response strategies of men and women to inform breeding

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    Open Access JournalThis study investigated the trait preferences for cassava in the context of climate change and conflict stressors among value-chain actors in Nigeria to strengthen social inclusion and the community-resilience outcomes from breeding programs. Multi-stage sampling procedures were used to select and interview male and female value-chain participants in the Osun, Benue and Abia States. The results indicated that farmers preferred cassava traits such as drought tolerance, early bulking, multiple-product use and in-ground storability to strengthen resilience. Climate change and challenges related to social change shaped the response strategies from both genders, and influenced trait preferences, including the early re-emergence of cassava leaves, stems that had ratooning potential, and especially the root milking that was important among female respondents. The major response strategies employed by men included frequent farm visits to prevent theft and engaging in non-agricultural livelihoods. Those employed by women included backyard farming, early harvesting, having preferences for food with fewer processing steps, and depending on remittances. The resilience capacity was higher for men than for women due to their better access to assets, as well as their abilities to relocate their farms and out-migrate in search of other livelihoods. Considering gendered cassava traits, and enhancing their resilience and response strategies, can complement efforts to make breeding more socially inclusive, resilient, and anticipatory to future challenges created by climate and related social changes
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