36 research outputs found
Understanding the Implications of Alternative Bioenergy Crops to Support Smallholder Farmers in Brazil
Smallholders constitute more than three quarters of the world’s farmers, and despite their numbers, they commonly lack opportunities to advance their development status. Bioenergy production and consumption can help sustain smallholders’ energy needs and generate employment and income, but it also raises concerns over social justice and equity, especially where crops used for bioenergy could also be used for food. This perspective paper is grounded in a literature review related to three different crops in Brazil: sugarcane, landrace maize and sweet potato. It seeks to determine if these crops offer the potential to support smallholder farmers’ development in a more equitable way, focusing on opportunities for their use in bioenergy. We review the literature to identify policies shaping the smallholder development context in relation to these crops, assessing whose knowledge informs policy and institutional decision making, and highlighting the policy attention afforded to the different crops from different sectors. We further evaluate the literature on each crop in relation to water use and calorific value (i.e., food and energy). Our review indicates that while sugarcane has received the most policy and institutional attention, its development is largely anchored in research and development investments that support large-scale commercial farms and agri-businesses. Smallholders have not benefited or had the opportunity to engage in relevant policy decision making for sugarcane cultivation. At the same time, smallholders hold valuable untapped knowledge on the cultivation of sweet potato and landrace maize, both of which have the potential to generate development opportunities for smallholders. Our review suggests that the environmental impact of landrace maize and sweet potato in terms of water use is significantly lower than sugarcane, while they can generate more calories for energy or food consumption and offer diversification opportunities. Despite that these alternative crops offer considerable untapped potential to support rural development, more research is still needed to harness these benefits. Changes are needed to address inequities in policies, institutions and the types of knowledge informing decision making. Such changes need to afford smallholder farmers greater recognition and participation in decision making, so that the distribution of benefits from the three study crops can reach them to support their development better
Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology
Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer’s mouse model
with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer’s
disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs,
including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease
in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore,
despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid patholog
Preservation of Quality of Life in HER2+ Metastatic Breast Cancer Patients Treated with Tucatinib or Placebo when Added to Trastuzumab and Capecitabine (The HER2CLIMB Trial)
Knock-in models related to Alzheimer’s disease: synaptic transmission, plaques and the role of microglia
Funder: Cure Alzheimer's Fund; doi: http://dx.doi.org/10.13039/100007625Funder: UK Dementia Research Institute (GB)Funder: Censejo Nacional de Ciencia Tecnilogia (MX)Funder: Alzheimerfonden; doi: http://dx.doi.org/10.13039/501100008599Funder: Dolby Family FundAbstract: Background: Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. Methods: AppNL-F and AppNL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer’s disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Results: Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in AppNL-F mice but was not evident in AppNL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Conclusions: Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer’s disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer’s disease
A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia
Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder
A Multi-disciplinary Commentary on Preclinical Research to investigate Vascular Contributions to Dementia
Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.</p