High-level dialogue deliberated solutions for gender equality and climate resilience in Africa

Climate change harms women disproportionately, exposing social and gender inequalities across the globe. At the same time, women are essential for transforming food systems that increase resilience, food and nutrition security and well-being for entire communities. That was the key message delivered at the 1st high-level dialogue on gender and climate change in Africa at the International Livestock Research Institute (ILRI) in Nairobi, Kenya, on 12 October 2022, convened by CGIAR’s Gender Equality (HER+) initiative, designed to address gender challenges in Global South food systems affected by climate change

Distant chaperones and N-glycan signals : new mechanisms of secretory pathway proteostasis

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2018.Page 176 blank. Cataloged from PDF version of thesis.Includes bibliographical references.Approximately one-third of all cellular proteins traverse the secretory pathway. After translation and folding in the endoplasmic reticulum (ER), proteins are transported through the Golgi to their final locations inside or outside of cells. At each step, proteins are helped by chaperones, which both shepherd proteins towards their native structures and serve as gatekeepers for export. Many proteins in the secretory pathway are also modified by installation of polysaccharides on specific asparagine residues. These N-glycans are installed in the ER as uniform precursors, but are trimmed and built up by Golgi glycan maturation enzymes into a striking array of epitopes. N-glycans act as a second mechanism to stabilize protein structure and prevent the release of misfolded proteins. Outside the cell, N-glycans on cell surfaces and secreted, soluble proteins allow cells to interact with each other, with their environment, and with distal tissues. During development, cells encounter physiological ER stress incurred by high levels of sustained protein production. Unresolved protein misfolding, on the other hand, results in pathological ER stress and tissue dysfunction. Prior work has used small model substrates to show that cells utilize secretory pathway chaperones and tune N-glycosylation to respond to ER stress. This thesis examines how cells use similar strategies to accommodate challenging cargoes such as collagen-1. In the human body, collagen-I constitutes the primary protein component of bone, skin, and other organs; collagen-I misfolding results in pathological ER stress and connective tissue diseases. We therefore set out 1) to identify cellular components required for collagen-I secretion that could be targeted to address disease and 2) to assess the effects of ER stress on both cellular N-glycan structures and individual glycoproteins. Here, we employ a high-throughput assay for collagen-I secretion and find that the cytosolic isoform of Hsp90 is required for collagen-I export. We also show that intracellular stress signaling alters the structures of cell surface and secreted N-glycans. Finally, we demonstrate that the collagen-I N-glycan buffers collagen-I folding against destabilizing mutations and ER stress. Our results identify potential therapeutic leads for collagen misfolding diseases and point to new mechanisms for maintaining secretory pathway proteostasis.by Madeline Y. Wong.Ph. D

Improving Senior Fitness Programs & Dementia Care (Canadian Centre for Activity & Aging)

Our team worked alongside the Canadian Centre for Activity and Aging (CCAA) to improve senior fitness programs and dementia care through volunteering at weekly exercise classes, assisting with fitness assessments, and creating two tangible deliverables. Our first deliverable was a Wordle; a tool for visualizing the modifiable risk factors of dementia. By consulting existing literature, we concluded that hearing loss, low education status, depression, and smoking were the main modifiable risk factors. This Wordle will be used for future research and educational purposes. Our next deliverables targeted the fitness aspect of the CCAA. We helped facilitate weekly instructor-led fitness classes and recorded our observations each time. We also conducted a functional fitness assessment to obtain baseline measurements of each participant’s functional abilities. Future measurements can then be compared with these values to evaluate the fitness classes’ efficacy at reducing or ameliorating declines in physical functioning. Some assessments required more time to complete than others, which reduced testing efficiency. Participants had the most difficulty with the timed up-and-go, 30-second arm curl, 30-second chair stand, and 2-minute step tests. Male participants were less likely to meet established standards compared with their female counterparts. Measurements were recorded using the Healthy Active Living Database (HAroLD) which was straightforward but difficult to use in real-time. Observations and recommendations were summarized with an infographic that will inform the CCAA’s management team about our contributions this term. Future students working with the CCAA can use our deliverables to improve the curriculum

Effects of vitamin D3 and its chemical analogs on the growth of Hodgkin’s lymphoma, in vitro

Objective: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin’s lymphoma (HL), a malignant pathology of B cell origin, in vitro. Results: Immunofluorescence staining showed the expression of VDR by primary Hodgkin’s (H) and Reed–Sternberg (RS)—HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, and L428. One-way analysis of variance (ANOVA) on data obtained from water-soluble tetrazolium 1 (WST-1) cell proliferation assay showed decreased cell growth in HDLM2 and L428, 72 h after treatment with 10 μM of either VD3 of VDAs. Western blot analyses showed that treatment of L428 cells with the VDAs (calcipotriol and EB1089) resulted in modest increases in nuclear accumulation of VDR (nuVDR) compared to either dimethyl sulfoxide (DMSO) or VD3 treatments. nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL

Loss of H2A.Z Is Not Sufficient to Determine Transcriptional Activity of Snf2-Related CBP Activator Protein or p400 Complexes

The p400 and SRCAP (Snf2-related CBP activator protein) complexes remodel chromatin by catalyzing deposition of histone H2A.Z into nucleosomes. This remodeling activity has been proposed as a basis for regulation of transcription by these complexes. Transcript levels of p21 or Sp1 mRNAs after knockdown of p400 or SRCAP reveals that each regulates transcription of these promoters differently. In this study, we asked whether deposition of H2A.Z within specific nucleosomes by p400 or SRCAP dictates transcriptional activity. Our data indicates that nucleosome density at specific p21 or Sp1 promoter positions is not altered by the loss of either remodeling complex. However, knockdown of SRCAP or p400 reduces deposition of H2A.Z∼50% into all p21 and Sp1 promoter nucleosomes. Thus, H2A.Z deposition is not targeted to specific nucleosomes. These results indicate that the deposition of H2A.Z by the p400 or SRCAP complexes is not sufficient to determine how each regulates transcription. This conclusion is further supported by studies that demonstrate a SRCAPΔATP mutant unable to deposit H2A.Z has similar transcriptional activity as wild-type SRCAP

Recertification guidelines for Massachusetts educators

The incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the effects of varying the surface properties (surface thickness and stiffness) of two ECMs, collagen I and Matrigel, on placental trophoblast cell morphology, viability, proliferation, and expression of markers involved in differentiation/syncytial fusion. Most notably, thicker Matrigel surfaces were found to induce the self-assembly of trophoblast cells into 3D spheroids that exhibited thickness-dependent changes in viability, proliferation, syncytial fusion, and gene expression profiles compared to two-dimensional cultures. Changes in F-actin organization, cell spread morphologies, and integrin and matrix metalloproteinase gene expression profiles, further reveal that the response to surface thickness may be mediated in part through cellular stiffness-sensing mechanisms. Our derivation of self-assembling trophoblast spheroid cultures through regulation of ECM surface alone contributes to a deeper understanding of cell-ECM interactions, and may be important for the advancement of in vitro platforms for research or diagnostics

Health visiting in the UK in light of the COVID-19 pandemic experience: (RReHOPE) findings from a realist review

Background Child health programmes in the United Kingdom offer every child and their family an evidence-based programme to support child health and development. During the COVID-19 pandemic, health visiting services in many areas were reduced to a partial service, with significant variability between and within the four United Kingdom countries. This study investigated the impact of the pandemic on health visiting services and developed recommendations for policy and practice. Objectives Conduct a realist review of relevant literature. Engage with key stakeholders in policy, practice and research across the United Kingdom. Identify recommendations for improving the organisation and delivery of health visiting services, with a focus on services being equitable, effective and efficient. Review methods The realist review followed Pawson’s five iterative steps and involved key stakeholder representatives at every step. We searched five electronic databases and references of included articles, as well as relevant organisational websites, to find quantitative, qualitative, mixed-methods and grey literature related to health visiting services in the United Kingdom during the COVID-19 pandemic. An assessment of their relevance to our initial programme theory determined inclusion in the review. Data were extracted, organised and presented as draft context, mechanism and outcome configurations. These were iteratively refined through meetings with 6 people with lived experience of caring for babies during the pandemic and 23 professional stakeholders. Context, mechanism and outcome configurations were then translated into findings and recommendations. Results One hundred and eighteen documents contributed to the review and collectively revealed the far-reaching, uneven and enduring impact of the COVID-19 pandemic on babies and families. Data uncovered significant concerns of families and practitioners amidst the pandemic, along with the service’s corresponding actions. These concerns and responses underscored the critical importance of fostering and sustaining trusting relationships between health visitors and families, as well as conducting holistic assessments for early intervention. Although we found minimal evidence of decision-making within organisational/managerial levels, the data illustrated the diverse and complex nature of health visiting work and the need for flexibility and resourcefulness. Limitations The primary limitation of this review was a lack of specific evidence from the United Kingdom nations other than England. There was also a lack of data focusing on changes during the COVID-19 pandemic at a local management level. Conclusions The needs of babies, children and families, and the delivery of services to support them, were not prioritised in the early phase of the pandemic response. Our data show that the health visiting service was concerned with maintaining visibility of all children, and especially supporting families with a new baby. Health visiting services adapted in numerous ways to respond to these concerns. Implications for policy and practice are presented, identified from our analysis and discussions with stakeholders. Future work The RReHOPE study is part of a jigsaw of evidence, which will provide a much stronger evidence base for future policy and practice. This realist review presents several areas for future research, including how health visiting is organised at local management level; how to optimise limited resources; factors affecting differing uptake in different regions; and analysis of the effectiveness of health visiting using large cohort studies