The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and ...as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the ...distribution of latent replication-competent HIV-1 within memory CD4+ T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization. FLIPS provides a genome-scale perspective that addresses the limitations of other methods that also genetically characterize the latent reservoir. Using FLIPS, we identified 5% of proviruses as intact and potentially replication competent. Intact proviruses were unequally distributed between T cell subsets, with effector memory cells containing the largest proportion of genetically intact HIV-1 proviruses. We identified multiple identical intact proviruses, suggesting a role for cellular proliferation in the maintenance of the latent HIV-1 reservoir.
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•FLIPS utilizes NGS to sequence and genetically characterize HIV-1 proviruses•FLIPS identifies genetically intact and likely replication-competent HIV-1 proviruses•Identical HIV-1 proviruses suggest maintenance of reservoir by cellular proliferation•Demonstrate the advantages of FLIPS over other common HIV-1 sequencing assays
Latent, replication-competent HIV-1 proviruses pose a significant barrier to an HIV-1 cure. Hiener et al. present the Full-Length Individual Proviral Sequencing (FLIPS) assay to reveal the distribution of genetically intact and potentially replication-competent HIV-1 proviruses in different T cell subsets isolated from individuals on long-term antiretroviral therapy.
A taskforce, under the auspices of The International Association of Gerontology and Geriatrics-Global Aging Research Network (IAGG-GARN) and the IAGG European Region Clinical Section, composed of ...experts from the fields of exercise science and geriatrics, met in Toulouse, in December 2015, with the aim of establishing recommendations of physical activity and exercise for older adults living in long-term care facilities (LTCFs). Due to the high heterogeneity in terms of functional ability and cognitive function that characterizes older adults living in LTCFs, taskforce members established 2 sets of recommendations: recommendations for reducing sedentary behaviors for all LTCF residents and recommendations for defining specific, evidence-based guidelines for exercise training for subgroups of LTCF residents. To promote a successful implementation of recommendations, taskforce experts highlighted the importance of promoting residents' motivation and pleasure, the key factors that can be increased when taking into account residents' desires, preferences, beliefs, and attitudes toward physical activity and exercise. The importance of organizational factors related to LTCFs and health care systems were recognized by the experts. In conclusion, this taskforce report proposes standards for the elaboration of strategies to increase physical activity as well as to prescribe exercise programs for older adults living in LTCFs. This report should be used as a guide for professionals working in LTCF settings.
T lymphocytes must regulate nutrient uptake to meet the metabolic demands of an immune response. Here we show that the intracellular supply of large neutral amino acids (LNAAs) in T cells was ...regulated by pathogens and the T cell antigen receptor (TCR). T cells responded to antigen by upregulating expression of many amino-acid transporters, but a single System L ('leucine-preferring system') transporter, Slc7a5, mediated uptake of LNAAs in activated T cells. Slc7a5-null T cells were unable to metabolically reprogram in response to antigen and did not undergo clonal expansion or effector differentiation. The metabolic catastrophe caused by loss of Slc7a5 reflected the requirement for sustained uptake of the LNAA leucine for activation of the serine-threonine kinase complex mTORC1 and for expression of the transcription factor c-Myc. Control of expression of the System L transporter by pathogens is thus a critical metabolic checkpoint for T cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Marine coastal (or ‘blue’) ecosystems provide valuable services to humanity and the environment, but global loss and degradation of blue ecosystems necessitates ecological restoration. However, blue ...restoration is an emerging field and is still relatively experimental and small-scale. Identification of the key barriers to scaling-up blue restoration will enable targeted problem solving and increase the likelihood of success. Here we describe the environmental, technical, social, economic, and political barriers to restoration of blue ecosystems, including saltmarsh, mangroves, seagrass, shellfish reefs, coral reefs, and kelp forests. We provide managers, practitioners, and decision-makers with solutions to construct barrier-informed blue restoration plans and illustrate these solutions through the use of case studies where barriers were overcome. We offer a way forward to build confidence in blue restoration for society, government, and restoration practitioners at larger and more ambitious scales.
The State of the Science in Spirituality and Palliative Care was convened to address the current landscape of research at the intersection of spirituality and palliative care and to identify critical ...next steps to advance this field of inquiry. Part I of the SOS-SPC two-part series focuses on questions of 1) What is spirituality? 2) What methodological and measurement issues are most salient for research in palliative care? And 3) What is the evidence relating spirituality and health outcomes? After describing current evidence we make recommendations for future research in each of the three areas of focus. Results show wide variance in the ways spirituality is operationalized and the need for definition and conceptual clarity in research in spirituality. Furthermore, the field would benefit from hypothesis-driven outcomes research based on a priori specification of the spiritual dimensions under investigation and their longitudinal relationship with key palliative outcomes, the use of validated measures of predictors and outcomes, and rigorous assessment of potential confounding variables. Finally, results highlight the need for research in more diverse populations.
When pets become pests Lockwood, Julie L; Welbourne, Dustin J; Romagosa, Christina M ...
Frontiers in ecology and the environment,
August 2019, Letnik:
17, Številka:
6
Journal Article
Recenzirano
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The annual trade in exotic vertebrates as pets is a multi-billion-dollar global business. Thousands of species, and tens of millions of individual animals, are shipped both internationally and within ...countries to satisfy this demand. Most research on the exotic pet trade has focused on its contribution to native biodiversity loss and disease spread. Here, we synthesize information across taxa and research disciplines to document the exotic pet trade’s contribution to vertebrate biological invasions. We show recent and substantial worldwide growth in the number of non-native animal populations introduced via this invasion pathway, which demonstrates a strong potential to increase the number of invasive animals in the future. Key to addressing the invasion threat of exotic pets is learning more about the socioeconomic forces that drive the massive growth in the exotic pet market and the socioecological factors that underlie pet release by owners. These factors likely vary according to cultural pet-keeping traditions across regions and whether purchases were legal or illegal. These gaps in our understanding of the exotic pet trade must be addressed in order to implement effective policy solutions.
The polyphyletic group of seagrasses shows an evolutionary history from early monocotyledonous land plants to the marine environment. Seagrasses form important coastal ecosystems worldwide and large ...amounts of seagrass detritus washed on beaches might also be valuable bioeconomical resources. Despite this importance and potential, little is known about adaptation of these angiosperms to the marine environment and their cell walls.
We investigated polysaccharide composition of nine seagrass species from the Mediterranean, Red Sea and eastern Indian Ocean. Sequential extraction revealed a similar seagrass cell wall polysaccharide composition to terrestrial angiosperms: arabinogalactans, pectins and different hemicelluloses, especially xylans and/or xyloglucans. However, the pectic fractions were characterized by the monosaccharide apiose, suggesting unusual apiogalacturonans are a common feature of seagrass cell walls. Detailed analyses of four representative species identified differences between organs and species in their constituent monosaccharide composition and lignin content and structure. Rhizomes were richer in glucosyl units compared to leaves and roots. Enhalus had high apiosyl and arabinosyl abundance, while two Australian species of Amphibolis and Posidonia, were characterized by high amounts of xylosyl residues. Interestingly, the latter two species contained appreciable amounts of lignin, especially in roots and rhizomes whereas Zostera and Enhalus were lignin-free. Lignin structure in Amphibolis was characterized by a higher syringyl content compared to that of Posidonia.
Our investigations give a first comprehensive overview on cell wall composition across seagrass families, which will help understanding adaptation to a marine environment in the evolutionary context and evaluating the potential of seagrass in biorefinery incentives.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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