Gendered analysis of ICT-enabled agricultural extension and advisory services : the case of Agro-Tech Smart Ex Model

This work was carried out with the aid of a grant from Canada’s International Development Research Centre (IDRC), and with financial support from the Government of Canada, provided through Global Affairs Canada (GAC)This paper deals with strategies to overcome barriers to agricultural extension and advisory services for women in agriculture. In targeting extension services towards women in the agricultural value chain, specific challenges cited in the study surveys are: small farm sizes due to lack of access to land; limited access to credit, input supply, and assets; and inadequate access to tractor services. Men have main access to silos and warehouses for grain storage. Other barriers are lack of access to radio and smart phones, lack of farmer organizations for women, and heavy workloads relating to farm work, care giving, and household chores

Appraisal of the Agro-Tech Smart Extension Model in Ghana : payment options and challenges in ICT-enabled extension services delivery

This work was carried out with the aid of a grant from Canada’s International Development Research Centre (IDRC), and with financial support from the Government of Canada, provided through Global Affairs Canada (GAC)The paper presents an overview of agricultural extension services in terms of providers, financing options and advisory services delivery. Farmer demand is high for ICT- enabled extension services delivery. The Grameen Foundation (GFUSA) and Farm Radio International have developed a mobile software application (AgroTech SmartEx) for smallholder farmer management purposes and to support better decision-making towards increased productivity. The AgroTech Model combines ICT-enabled extension and advisory services with direct to farmer interactive radio. Survey data from 400 farmers indicates a high performance rating for the AgroTech Smart Ex Model, where over 70% of respondents consider it to be excellent

Private sector-led business model for meeting changing needs of agribusiness value chains actors in Ghana based on mobile-based ICT-enabled field agents

This work was carried out with the aid of a grant from Canada’s International Development Research Centre (IDRC), and with financial support from the Government of Canada, provided through Global Affairs Canada (GAC)The article reviews research findings where farmers expressed needs for various support services including credit/finance, information on markets, prices and weather, input supply services and keeping of farm records. In Ghana, the government-funded agricultural extension system limits activities to technology transfer and education through training, demonstrations and visits. Other services such as inputs and machinery services are provided by the private sector. Based on the gaps between public and private inputs, an Integrated Business Services Delivery Model is proposed, that is national in character with a three-tier structure consisting of a Master Platform, Digital Solution Providers (DSPs) and Agribusiness Service Providers

Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation.

Mutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet. Examining the muscle biopsy of our index ALS8 patient of European origin revealed globular accumulations of VAPB aggregates co-localised with autophagy markers LC3 and p62 in partially atrophic and atrophic muscle fibres. In line with this skin fibroblasts obtained from the same patient showed accumulation of P56S-VAPB aggregates together with LC3 and p62. Detailed investigations of autophagic flux in cell culture models revealed that P56S-VAPB alters both initial and late steps of the autophagy pathway. Accordingly, electron microscopy complemented with live cell imaging highlighted the impaired fusion of accumulated autophagosomes with lysosomes in cells expressing P56S-VAPB. Consistent with these observations, neuropathological studies of brain and spinal cord of P56S-VAPB transgenic mice revealed signs of neurodegeneration associated with altered protein quality control and defective autophagy. Autophagy and RBP homeostasis are interdependent, as demonstrated by the cytoplasmic mis-localisation of several RBPs including pTDP-43, FUS, Matrin 3 which often sequestered with P56S-VAPB aggregates both in cell culture and in the muscle biopsy of the ALS8 patient. Further confirming the notion that aggregation of the RBPs proceeds through the stress granule (SG) pathway, we found persistent G3BP- and TIAR1-positive SGs in P56S-VAPB expressing cells as well as in the ALS8 patient muscle biopsy. We conclude that P56S-VAPB-ALS8 involves a cohesive pathomechanism of aberrant RBP homeostasis together with dysfunctional autophagy

Loss of PML Nuclear Bodies in Familial Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The critical genetic players of ALS and FTD are the TARDBP, FUS and C9orf72 genes, whose protein products, TDP-43, FUS and the C9orf72-dipeptide repeat proteins, accumulate in form of cytoplasmic inclusions. The majority of the studies focus on the understanding of how cells control TDP-43 and FUS aggregation in the cytoplasm, overlooking how dysfunctions occurring at the nuclear level may influence the maintenance of protein solubility outside of the nucleus. However, protein quality control (PQC) systems that maintain protein homeostasis comprise a cytoplasmic and a nuclear arm that are interconnected and share key players. It is thus conceivable that impairment of the nuclear arm of the PQC may have a negative impact on the cytoplasmic arm of the PQC, contributing to the formation of the cytoplasmic pathological inclusions. Here we focused on two stress-inducible condensates that act as transient deposition sites for misfolding-prone proteins: Promyelocytic leukemia protein (PML) nuclear bodies (PML-NBs) and cytoplasmic stress granules (SGs). Upon stress, PML-NBs compartmentalize misfolded proteins, including defective ribosomal products (DRiPs), and recruit chaperones and proteasomes to promote their nuclear clearance. SGs transiently sequester aggregation-prone RNA-binding proteins linked to ALS-FTD and mRNAs to attenuate their translation. We report that PML assembly is impaired in the human brain and spinal cord of familial C9orf72 and FUS ALS-FTD cases. We also show that defective PML-NB assembly impairs the compartmentalization of DRiPs in the nucleus, leading to their accumulation inside cytoplasmic SGs, negatively influencing SG dynamics. Although it is currently unclear what causes the decrease of PML-NBs in ALS-FTD, our data highlight the existence of a cross-talk between the cytoplasmic and nuclear PQC systems, whose alteration can contribute to SG accumulation and cytoplasmic protein aggregation in ALS-FTD

PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD.

ER stress signaling is linked to the pathophysiological and clinical disease manifestations in amyotrophic lateral sclerosis (ALS). Here, we have investigated ER stress-induced adaptive mechanisms in C9ORF72-ALS/FTD, focusing on uncovering early endogenous neuroprotective mechanisms and the crosstalk between pathological and adaptive responses in disease onset and progression. We provide evidence for the early onset of ER stress-mediated adaptive response in C9ORF72 patient-derived motoneurons (MNs), reflected by the elevated increase in GRP75 expression. These transiently increased GRP75 levels enhance ER-mitochondrial association, boosting mitochondrial function and sustaining cellular bioenergetics during the initial stage of disease, thereby counteracting early mitochondrial deficits. In C9orf72 rodent neurons, an abrupt reduction in GRP75 expression coincided with the onset of UPR, mitochondrial dysfunction and the emergence of PolyGA aggregates, which co-localize with GRP75. Similarly, the overexpression of PolyGA in WT cortical neurons or C9ORF72 patient-derived MNs led to the sequestration of GRP75 within PolyGA inclusions, resulting in mitochondrial calcium (Ca2+) uptake impairments. Corroborating these findings, we found that PolyGA aggregate-bearing human post-mortem C9ORF72 hippocampal dentate gyrus neurons not only display reduced expression of GRP75 but also exhibit GRP75 sequestration within inclusions. Sustaining high GRP75 expression in spinal C9orf72 rodent MNs specifically prevented ER stress, normalized mitochondrial function, abrogated PolyGA accumulation in spinal MNs, and ameliorated ALS-associated behavioral phenotype. Taken together, our results are in line with the notion that neurons in C9ORF72-ALS/FTD are particularly susceptible to ER-mitochondrial dysfunction and that GRP75 serves as a critical endogenous neuroprotective factor. This neuroprotective pathway, is eventually targeted by PolyGA, leading to GRP75 sequestration, and its subsequent loss of function at the MAM, compromising mitochondrial function and promoting disease onset

Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS

Nuclear to cytoplasmic mislocalization and aggregation of multiple RNA-binding proteins (RBPs), including FUS, are the main neuropathological features of the majority of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobular degeneration (FTLD). In ALS-FUS, these aggregates arise from disease-associated mutations in FUS, whereas in FTLD-FUS, the cytoplasmic inclusions do not contain mutant FUS, suggesting different molecular mechanisms of FUS pathogenesis in FTLD that remain to be investigated. We have previously shown that phosphorylation of the C-terminal Tyr526 of FUS results in increased cytoplasmic retention of FUS due to impaired binding to the nuclear import receptor TNPO1. Inspired by the above notions, in the current study we developed a novel antibody against the C-terminally phosphorylated Tyr526 FUS (FUS$^{p-Y526}$) that is specifically capable of recognizing phosphorylated cytoplasmic FUS, which is poorly recognized by other commercially available FUS antibodies. Using this FUS$^{p-Y526}$ antibody, we demonstrated a FUS phosphorylation-specific effect on the cytoplasmic distribution of soluble and insoluble FUS$^{p-Y526}$ in various cells and confirmed the involvement of the Src kinase family in Tyr526 FUS phosphorylation. In addition, we found that FUS$^{p-Y526}$ expression pattern correlates with active pSrc/pAbl kinases in specific brain regions of mice, indicating preferential involvement of cAbl in the cytoplasmic mislocalization of FUS$^{p-Y526}$ in cortical neurons. Finally, the pattern of immunoreactivity of active cAbl kinase and FUS$^{p-Y526}$ revealed altered cytoplasmic distribution of FUS$^{p-Y526}$ in cortical neurons of post-mortem frontal cortex tissue from FTLD patients compared with controls. The overlap of FUS$^{p-Y526}$ and FUS signals was found preferentially in small diffuse inclusions and was absent in mature aggregates, suggesting possible involvement of FUS$^{p-Y526}$ in the formation of early toxic FUS aggregates in the cytoplasm that are largely undetected by commercially available FUS antibodies. Given the overlapping patterns of cAbl activity and FUS$^{p-Y526}$ distribution in cortical neurons, and cAbl induced sequestration of FUS$^{p-Y526}$ into G3BP1 positive granules in stressed cells, we propose that cAbl kinase is actively involved in mediating cytoplasmic mislocalization and promoting toxic aggregation of wild-type FUS in the brains of FTLD patients, as a novel putative underlying mechanism of FTLD-FUS pathophysiology and progression

Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the <i>rd10</i> Mouse Model of Retinitis Pigmentosa (RP)

The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa (RP) pathomechanisms. It offers a rather unique opportunity to study trans-neuronal degeneration because the cell populations in question are separated anatomically and the mutated Pde6b gene is selectively expressed in rod photoreceptors. We hypothesized that RNA binding protein (RBP) aggregation and abnormal autophagy might serve as early pathogenic events, damaging non-photoreceptor retinal cell types that are not primarily targeted by the Pde6b gene defect. We used a combination of immunohistochemistry (DAB, immunofluorescence), electron microscopy (EM), subcellular fractionation, and Western blot analysis on the retinal preparations obtained from both rd10 and wild-type mice. We found early, robust increases in levels of the protective endoplasmic reticulum (ER) calcium (Ca2+) buffering chaperone Sigma receptor 1 (SigR1) together with other ER-Ca2+ buffering proteins in both photoreceptors and non-photoreceptor neuronal cells before any noticeable photoreceptor degeneration. In line with this, we found markedly altered expression of the autophagy proteins p62 and LC3, together with abnormal ER widening and large autophagic vacuoles as detected by EM. Interestingly, these changes were accompanied by early, prominent cytoplasmic and nuclear aggregation of the key RBPs including pTDP-43 and FET family RBPs and stress granule formation. We conclude that progressive neurodegeneration in the rd10 mouse retina is associated with early disturbances of proteostasis and autophagy, along with abnormal cytoplasmic RBP aggregation

Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations

Heterozygous BICD2 gene mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED).status: publishe