Display omitted
•Monomers are made inside of cells and exported to the wall by unknown mechanism(s).•Possible mechanisms include transporters such as ATP-binding cassette transporters.•Diffusion of ...monomers through membranes, driven by polymer formation, is possible.•In gymnosperms, monolignol glucosides represent a possible alternate route to lignin.•Cells can export lignin monomers into the shared walls of neighboring cells.
Lignin is a highly abundant polymer in plant cell walls that is essential for land plants’ ability to stand upright and transport water. Inside plant cells, lignin monomers, called monolignols, are made from phenylalanine via a multistep pathway. In the cell wall, monomers move freely, until they encounter stationary oxidative enzymes that determine where the lignin polymer forms. However, it remains unclear how lignin monomers are trafficked from inside the cell to the cell wall. Although multiple lines of circumstantial evidence implicate transporters, additional possible mechanisms include the diffusion of monomers across lipid bilayers and the release of monolignol glucosides stored in vacuoles. There are therefore potentially diverse and overlapping mechanisms of monolignol export.
Mutations in VCP cause multisystem degeneration impacting the nervous system, muscle, and/or bone. Patients may present with ALS, Parkinsonism, frontotemporal dementia, myopathy, Paget’s disease, or ...a combination of these. The disease mechanism is unknown. We developed a Drosophila model of VCP mutation-dependent degeneration. The phenotype is reminiscent of PINK1 and parkin mutants, including a pronounced mitochondrial defect. Indeed, VCP interacts genetically with the PINK1/parkin pathway in vivo. Paradoxically, VCP complements PINK1 deficiency but not parkin deficiency. The basis of this paradox is resolved by mechanistic studies in vitro showing that VCP recruitment to damaged mitochondria requires Parkin-mediated ubiquitination of mitochondrial targets. VCP recruitment coincides temporally with mitochondrial fission, and VCP is required for proteasome-dependent degradation of Mitofusins in vitro and in vivo. Further, VCP and its adaptor Npl4/Ufd1 are required for clearance of damaged mitochondria via the PINK1/Parkin pathway, and this is impaired by pathogenic mutations in VCP.
► VCP functions downstream of PINK1 in the PINK1/Parkin pathway ► VCP is recruited to mitochondria in response to Parkin-mediated ubiquitination ► VCP and Npl4/Ufd1 are required for clearance of damaged mitochondria ► Disease mutations in VCP impair its ability to support the PINK1/Parkin pathway
Mutations in VCP cause diseases in the nervous system, muscle, and/or bone through an unknown mechanism. Kim et al. demonstrate that VCP is an essential component of the PINK1/Parkin pathway of mitochondrial quality control, and disease mutations impair this function.
Vascular plants (Tracheophytes) have adapted to a variety of environments ranging from arid deserts to tropical rainforests, and now comprise >250 000 species. While they differ widely in appearance ...and growth habit, all of them share a similar specialized tissue system (vascular tissue) for transporting water and nutrients throughout the organism. Plant vascular systems connect all plant organs from the shoot to the root, and are comprised of two main tissue types, xylem and phloem. In this review we examine the current state of knowledge concerning the process of vascular tissue formation, and highlight important mechanisms underlying key steps in vascular cell type specification, xylem and phloem tissue patterning, and, finally, the differentiation and maturation of specific xylem cell types.
This mixed methods study examined preservice teacher perspectives on the impact of using untethered lecture capture (ULC) as an instructional technology in a teacher preparation course, both on ...learning experiences as students and confidence using technology as teachers. Results found statistically significant (p < .05) increases in confidence using technology as a teaching tool. Additionally, Darling-Hammond et al.'s (2018) Teacher Preparation for Deeper Learning framework was utilized to analyze qualitative data to explore the impact of ULC on preservice teacher learning. Challenges and recommendations for effective implementation of ULC, based on participant feedback, are provided. This study contributes to research on using technology in teacher preparation programs to enhance the teaching and learning process for preservice educators and is grounded in the TPACK model (Mistra & Koehler, 2009).
The conservation of freshwater is of both global and national importance, and in the United States, agriculture is one of the largest consumers of this resource. Reduction of the strain farming puts ...on local surface or groundwater is vital for ensuring resilience in the face of climate change, and one possible option is to irrigate with a combination of freshwater and reclaimed water from municipal wastewater treatment facilities. However, this wastewater can contain pathogens that are harmful to human health, such as Legionella pneumophila, which is a bacterium that can survive aerosolization and airborne transportation and cause severe pneumonia when inhaled. To assess an individual adult's risk of infection with L. pneumophila from a single exposure to agricultural spray irrigation, a quantitative microbial risk assessment was conducted for a scenario of spray irrigation in central Illinois, for the growing seasons in 2017, 2018, and 2019. The assessment found that the mean risk of infection for a single exposure exceeded the safety threshold of 10–6 infections/exposure up to 1 km from a low‐pressure irrigator and up to 2 km from a high‐pressure irrigator, although no median risk exceeded the threshold for any distance or irrigator pressure. These findings suggest that spray irrigation with treated municipal wastewater could be a viable option for reducing freshwater consumption in Midwest farming, as long as irrigation on windy days is avoided and close proximity to the active irrigator is limited.
Habitat loss and fragmentation, particularly because of agrarian and urban expansions, are threatening biodiversity worldwide. Paraguay is predicted to lose all its primary moist forests by 2028. The ...most endangered habitat in Paraguay is the Upper Paraná Atlantic Forest (BAAPA), which has been decimated by industrial agriculture in the past 60 years. The hooded capuchin (
Sapajus cay
) is the best-known Paraguayan primate and the only species mostly restricted to the remaining BAAPA. We used local (defined as people living in Paraguay) knowledge about the known presence of the species in a habitat fragment to assess whether species’ presence was associated with forest cover in fragments by using a binomial general linear model (GLM). Using the results of the GLM, we then assessed how forest cover changed through the hooded capuchin range and its predicted range in Paraguay using Global ForestWatch forest cover prediction for 2000 to 2019. The GLM showed that the presence of hooded capuchins required predominance of forest cover with the monkey being 80% likely to be present for 56% cover and 90% for 70% cover. The capuchin has lost 23% of highly suitable habitat across its whole range and 58% in Paraguay. Suitable habitat for hooded capuchin monkeys is, therefore, decreasing across the full extent of the species. In Paraguay, the remaining habitat is being fragmented and degraded and distance between fragments is increasing. Because the situation in Paraguay is critical, we recommend that the capuchin is classified as Vulnerable by the International Union for the Conservation of Nature and Natural Resources (IUCN) Red List at a national level under criterion B1, b(i), b(ii), and b(iii). Predictions across the species range warrant at least a classification of Near Threatened for the species. These results demonstrate that the conservation situation faced by a primate species can differ greatly depending on local, national, and range wide political and social situations. Therefore, we recommend that national assessments are performed for species that are found in multiple countries in order to gain a true picture of threats a species faces.
Abstract Although mutations within the TREM2 gene have been robustly associated with Alzheimer’s disease, it is not known whether alterations in the regulation of this gene are also involved in ...pathogenesis. Here we present data demonstrating increased DNA methylation in the superior temporal gyrus in AD brain at a CpG site located 289bp upstream of the transcription start site of the TREM2 gene in three independent study cohorts using two different technologies (Illumina Infinium 450K methylation beadchip and pyrosequencing). A meta-analysis across all three cohorts reveals consistent Alzheimer’s disease associated hypermethylation (p=3.47E-08). This study highlights that extending genetic studies of TREM2 in Alzheimer’s disease to investigate epigenetic changes may nominate additional mechanisms by which disruption to this gene increases risk.
Recent epigenome-wide association studies in Alzheimer's disease have highlighted consistent robust neuropathology-associated DNA hypermethylation of the ankyrin 1 (ANK1) gene in the cortex. The ...extent to which altered ANK1 DNA methylation is also associated with other neurodegenerative diseases is not currently known. In the present study, we used bisulfite pyrosequencing to quantify DNA methylation across 8 CpG sites within a 118 bp region of the ANK1 gene across multiple brain regions in Alzheimer's disease, Vascular dementia, Dementia with Lewy bodies, Huntington's disease, and Parkinson's disease. We demonstrate disease-associated ANK1 hypermethylation in the entorhinal cortex in Alzheimer's disease, Huntington's disease, and Parkinson's disease, whereas in donors with Vascular dementia and Dementia with Lewy bodies, we observed elevated ANK1 DNA methylation only in individuals with coexisting Alzheimer's disease pathology. We did not observe any disease-associated differential ANK1 DNA methylation in the striatum in Huntington's disease or the substantia nigra in Parkinson's disease. Our data suggest that ANK1 is characterized by region and disease-specific differential DNA methylation in multiple neurodegenerative diseases.
•We analyzed brain DNA methylation levels across a 118 bp region of the ANK1 gene.•We looked in multiple neurodegenerative diseases compared to controls.•DNA hypermethylation was seen in the entorhinal cortex in AD, HD and PD.•DNA hypermethylation in DLB and VaD was only in donors with co-existing AD.•No disease-associated changes were seen in regions of primary pathology in HD or PD.
Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER
) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these ...mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with
assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER
breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER
breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER
breast cancers in obese postmenopausal women. SIGNIFICANCE: These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.
Lignin is a critical structural component of plants, providing vascular integrity and mechanical strength. Lignin precursors (monolignols) must be exported to the extracellular matrix where random ...oxidative coupling produces a complex lignin polymer. The objectives of this study were twofold: to determine the timing of lignification with respect to programmed cell death and to test if nonlignifying xylary parenchyma cells can contribute to the lignification of tracheary elements and fibers. This study demonstrates that lignin deposition is not exclusively a postmortem event, but also occurs prior to programmed cell death. Radiolabeled monolignols were not detected in the cytoplasm or vacuoles of tracheary elements or neighbors. To experimentally define which cells in lignifying tissues contribute to lignification in intact plants, a microRNA against CINNAMOYL CoA-REDUCTASE1 driven by the promoter from CELLULOSE SYNTHASE7 (ProCESA7:miRNA CCR1) was used to silence monolignol biosynthesis specifically in cells developing lignified secondary cell walls. When monolignol biosynthesis in ProCESA7:miRNA CCR1 lines was silenced in the lignifying cells themselves, but not in the neighboring cells, lignin was still deposited in the xylem secondary cell walls. Surprisingly, a dramatic reduction in cell wall lignification of extraxylary fiber cells demonstrates that extraxylary fibers undergo cell autonomous lignification.
PDF
