606 research outputs found

    Assessing the potential for managed aquifer recharge (MAR) of the Cape Flats Aquifer

    Get PDF
    This paper discusses the potential use of ‘managed aquifer recharge’ (MAR) in Cape Town to provide additional water supplies to the city that are fit-for-purpose. The paper investigates the feasibility of implementing MAR by simulating the artificial recharge of winter stormwater into the Cape Flats Aquifer (CFA), an extensive sandy, unconfined aquifer that covers most of metropolitan Cape Town’s urban landscape. The objective is to assess the storage capacity and supply potential of two MAR sites by modelling various scenarios in order to determine the feasibility of MAR as a viable strategy for achieving improved water security by augmenting groundwater water supply. The selected scenarios demonstrated that MAR could be used to minimise the risk of seawater intrusion and maximise the amount of water available for abstraction from the CFA. Six MAR scenarios provided strong evidence to suggest that there is sufficient storage capacity within the CFA for using stormwater to improve the wellfield yield in two regions of the CFA and which can sustainably yield approximately 18 Mm3per year. The study concluded that the use of stormwater or treated wastewater could be deliberately used to recharge the CFA and as a viable option in support of the City of Cape Town’s intention to establish a water-resilient city by 2030

    Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

    Get PDF
    Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

    Examining Social Isolation and Loneliness: Cross-Sectional Needs Assessment among Community-Dwelling Older Adults

    Get PDF
    Social isolation and loneliness (SIL) represent a growing public health and public policy concern, particularly among older adults. Half of older adults over the age of 60 are at risk of social isolation and one-third experience loneliness. SIL is a particular concern for individuals aging-in-place in low-density and rural areas. SIL increases the risk of premature death from all causes in older individuals, and results in 6.7billioninadditionalMedicarespendingannually.Tennesseeisrankedtenthinthenationforriskofsocialisolation.Strategiestopromotesocialconnectionsareacriticalstepindesigningagefriendlycommunities.Acrosssectionalsurveyofaconveniencesampleofolderadults(62yearsandolder)livinginaffordablehousingapartmentcomplexesinHawkinsCounty,TNwasconductedinFebruaryandMarch2023.Loneliness(UCLA3itemLonelinessScale),socialisolation(LubbenSocialNetworkScale6item),andsenseofcommunity(BriefSenseofCommunityScale)wereassessed.Datawerealsogatheredondemographiccharacteristics,healthstatus,socialengagement,andstrategiestosupportolderadultsaginginplace.Datafrom82participantsaged62to95(73.14meanage;SD=7.00)wereanalyzed.Themajorityofparticipantswerefemale(676.7 billion in additional Medicare spending annually. Tennessee is ranked tenth in the nation for risk of social isolation. Strategies to promote social connections are a critical step in designing age-friendly communities. A cross-sectional survey of a convenience sample of older adults (62 years and older) living in affordable housing apartment complexes in Hawkins County, TN was conducted in February and March 2023. Loneliness (UCLA 3-item Loneliness Scale), social isolation (Lubben Social Network Scale 6-item), and sense of community (Brief Sense of Community Scale) were assessed. Data were also gathered on demographic characteristics, health status, social engagement, and strategies to support older adults aging-in-place. Data from 82 participants aged 62 to 95 (73.14 mean age; SD = 7.00) were analyzed. The majority of participants were female (67%), non-Hispanic White (93%), lived alone (90%), and were retired (84%) with an average annual income less than or equal to 14,225 (43%). Nearly half (44%) report their health as fair or poor compared to others their age and 79% of participants have 4 or more chronic conditions. Overall mean loneliness score indicated moderate loneliness (mean = 4.9; SD = 2.08; range 0-9). 48% were at risk of social isolation (mean = 13.35; SD = 6.14; range 0-29). The total mean sense of community score was moderate (mean = 22.9; SD = 1.09; range 0-40). Factors associated with SIL will be analyzed using Pearson’s correlation test. Strategies to promote social engagement will be discussed. Living and growing older in rural communities is considered a primary risk factor for SIL. To support healthy aging, local efforts must include strategies to increase social engagement for rural older adults and their communities. Results from this needs assessment will be used to generate recommendations that can be used to improve social connectedness among older adults living in Hawkins County, TN

    Solid state supramolecular structure of diketopyrrolopyrrole chromophores: correlating stacking geometry with visible light absorption

    Get PDF
    Mono- and di-alkylated 1,4-diketo-3,6-dithiophenylpyrrolo[3-4-c]pyrrole derivatives (TDPPs) have been synthesised and their solid state packing and absorption properties have been correlated. In this library of compounds the bulkier substituents distort the geometry of the chromophores and shift the lowest energy absorption band as a consequence of reduced π–π stacking and inter-chromophore overlap. Longitudinal displacement of the conjugated core is affected by donor–acceptor intermolecular interactions and twisting of the thiophene ring out of the plane of the DPP core, whereas lateral displacement was correlated to distortion of the NLactam–C(R) bond out of the plane of the DPP core. The di-substituted TDPP with hexyl units exhibit high molecular planarity, strong close packing of the conjugated core and significant red shift of the maximum of absorption in the solid, whereas the mono-substituted compounds with hexyl and ethyl acetate units are the least distorted of the series because of strong intermolecular hydrogen bonding that increases the molecular overlap and planarity of the chromophores. Therefore the family of mono-substituted TDPPs and more specifically the ones with ethyl acetate substituents show good potential for modulating the molecular geometry and optimizing the charge transport in materials for organic electronic applications

    Strongly exchange-coupled triplet pairs in an organic semiconductor

    Get PDF
    From biological complexes to devices based on organic semiconductors, spin interactions play a key role in the function of molecular systems. For instance, triplet-pair reactions impact operation of organic light-emitting diodes as well as photovoltaic devices. Conventional models for triplet pairs assume they interact only weakly. Here, using electron spin resonance, we observe long-lived, strongly-interacting triplet pairs in an organic semiconductor, generated via singlet fission. Using coherent spin-manipulation of these two-triplet states, we identify exchange-coupled (spin-2) quintet complexes co-existing with weakly coupled (spin-1) triplets. We measure strongly coupled pairs with a lifetime approaching 3 µs and a spin coherence time approaching 1 µs, at 10 K. Our results pave the way for the utilization of high-spin systems in organic semiconductors.Gates-Cambridge Trust, Winton Programme for the Physics of Sustainability, Freie Universität Berlin within the Excellence Initiative of the German Research Foundation, Engineering and Physical Sciences Research Council (Grant ID: EP/G060738/1)This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nphys3908

    Modulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage.

    Get PDF
    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Engineering organs and tissues with the spatial composition and organisation of their native equivalents remains a major challenge. One approach to engineer such spatial complexity is to recapitulate the gradients in regulatory signals that during development and maturation are believed to drive spatial changes in stem cell differentiation. Mesenchymal stem cell (MSC) differentiation is known to be influenced by both soluble factors and mechanical cues present in the local microenvironment. The objective of this study was to engineer a cartilaginous tissue with a native zonal composition by modulating both the oxygen tension and mechanical environment thorough the depth of MSC seeded hydrogels. To this end, constructs were radially confined to half their thickness and subjected to dynamic compression (DC). Confinement reduced oxygen levels in the bottom of the construct and with the application of DC, increased strains across the top of the construct. These spatial changes correlated with increased glycosaminoglycan accumulation in the bottom of constructs, increased collagen accumulation in the top of constructs, and a suppression of hypertrophy and calcification throughout the construct. Matrix accumulation increased for higher hydrogel cell seeding densities; with DC further enhancing both glycosaminoglycan accumulation and construct stiffness. The combination of spatial confinement and DC was also found to increase proteoglycan-4 (lubricin) deposition toward the top surface of these tissues. In conclusion, by modulating the environment through the depth of developing constructs, it is possible to suppress MSC endochondral progression and to engineer tissues with zonal gradients mimicking certain aspects of articular cartilage.Funding was provided by Science Foundation Ireland (President of Ireland Young Researcher Award: 08/Y15/B1336) and the European Research Council (StemRepair – Project number 258463)

    Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult

    Get PDF
    Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01AR60361, R01AR061988, P41EB002520). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ART was supported by a National Science Foundation Graduate Fellowship

    Gene duplication and divergence produce divergent MHC genotypes without disassortative mating

    Get PDF
    Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leach\u27s storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good statistical power, we consistently found random assortment of mates at MHC. Despite random mating, birds had MHC genotypes with functionally diverged alleles, averaging 13 amino acid differences in pairwise comparisons of exon 2 alleles within individuals. To test whether this high MHC diversity in individuals is driven by evolutionary divergence of the two duplicated genes, we built a phylogenetic permutation model. The model showed that genotypic diversity was strongly impacted by sequence divergence between the most common allele of each gene, with a smaller additional impact of monophyly of the two genes. Divergence of allele sequences between genes may have reduced the benefits of actively seeking MHC-dissimilar mates, in which case the evolutionary history of duplicated genes is shaping the adaptive landscape of sexual selection

    Intervertebral disc degeneration and regeneration: a motion segment perspective

    Get PDF
    Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective

    Excretion patterns of coccidian oocysts and nematode eggs during the reproductive season in Northern Bald Ibis (Geronticus eremita)

    Get PDF
    Individual reproductive success largely depends on the ability to optimize behaviour, immune function and the physiological stress response. We have investigated correlations between behaviour, faecal steroid metabolites, immune parameters, parasite excretion patterns and reproductive output in a critically endangered avian species, the Northern Bald Ibis (Geronticus eremita). In particular, we related haematocrit, heterophil/lymphocyte ratio, excreted immune-reactive corticosterone metabolites and social behaviour with parasite excretion and two individual fitness parameters, namely, number of eggs laid and number of fledglings. We found that the frequency of excretion of parasites’ oocysts and eggs tended to increase with ambient temperature. Paired individuals excreted significantly more samples containing nematode eggs than unpaired ones. The excretion of nematode eggs was also significantly more frequent in females than in males. Individuals with a high proportion of droppings containing coccidian oocysts were more often preened by their partners than individuals with lower excretion rates. We observed that the more eggs an individual incubated and the fewer offspring fledged, the higher the rates of excreted samples containing coccidian oocysts. Our results confirm that social behaviour, physiology and parasite burden are linked in a complex and context-dependent manner. They also contribute background information supporting future conservation programmes dealing with this critically endangered species
    corecore