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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Zhang, Fengling, et al.
(author)
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Soluble polythiophenes with pendant fullerene groups as double cable materials for photodiodes
- 2001
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In: Advanced Materials. - 0935-9648 .- 1521-4095. ; 13:24, s. 1871-
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Journal article (peer-reviewed)abstract
- A novel "double cable" material for photodiodes, containing both electron- and hole-transporting functional groups, is obtained by co-polymerization of thiophenes that bear a covalently linker-bound fullerene (see Figure). Even at 14% of fullerene substitution, the order of the main polythiophene chain is not seriously disturbed.
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- M. Siribbal, Shifaa, et al.
(author)
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Biocompatible Hollow Gadolinium Oxide Nanocarriers for the Transport of Bioactive Molecules to Cells
- 2024
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In: ACS Applied Nano Materials. - : AMER CHEMICAL SOC. - 2574-0970.
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Journal article (peer-reviewed)abstract
- Integrating imaging and therapeutic capabilities into a single entity can offer enhanced diagnostic accuracy and treatment efficacy in clinically effective formulations. Due to the diversity of chemical structures and/or limited solubility of inhibitors or fluorophores, it is essential to employ a robust delivery carrier that can facilitate drug absorption and distribution during its circulation in the blood. This study explores the potential of hollow gadolinium oxide (Gd2O3) nanocarriers in imaging and drug delivery applications. The citric acid (CA)-capped hollow gadolinium oxide nanocarriers were synthesized via urea-assisted precipitation and hydrothermal methods using carbon spheres as sacrificial templates. The resulting nanosized hollow spheres displayed a spherical morphology and demonstrated relaxation rates in the longitudinal and transverse directions, as indicated by their r 1 and r(2) values of 1.8 and 5.3 s(-1) mM(-1), respectively. To mimic the physiological conditions, the hollow gadolinium oxide spheres were loaded separately with antibiotic sparfloxacin and the azo dye Congo red at neutral pH (7.4) and body temperature (37 degrees C). The CR-loaded nanospheres exhibited a time-dependent internalization behavior with HeLa cells, suggesting their imaging potential for intracellular drug delivery. Furthermore, the SP-loaded nanospheres demonstrated antimicrobial activity against both Gram-positive and Gram-negative bacteria, demonstrating their therapeutic potential against bacterial infections. To mitigate the risk of leaching of Gd3+ ions and their inherent toxicity, a CA coating was applied to hollow gadolinium oxide surface which resulted in outstanding cell viability of the surface functionalized nanocarriers. In addition, the CA coating offered additional support for the increased encapsulation and continuous release of drug molecules until 1 week (168 h). The characterization data provide evidence for the potential of CA-capped hollow gadolinium oxide spheres as positive MR contrast agents and their applicability as safe and controlled drug carriers.
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- Scherhaufer, S., et al.
(author)
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Environmental assessment of the valorisation and recycling of selected food production side flows
- 2020
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In: Resources, Conservation and Recycling. - : Elsevier B.V.. - 0921-3449 .- 1879-0658. ; 161
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Journal article (peer-reviewed)abstract
- Residues from the food manufacturing industry require management options with the best overall environmental outcome. The identification of sustainable solutions depends however, on many influencing factors such as energy input, transport distance, and substituted product. This study shows the influence of the choice of substituted products on the overall greenhouse gas (GHG) emissions for three specific food side-flows and their treatment in the European Union: animal blood, apple pomace and brewers’ spent grain (BSG). In a direct comparison of possible treatment options, it is notable that the conversion to food ingredients (valorisation) does not always result in reduced environmental net impacts (GHG savings), which means that other options at lower levels of the waste hierarchy might be more beneficial to the environment. The further use of apple pomace or BSG for the production of food ingredients is only advantageous if the processing emissions are smaller than the emissions from the substituted products. The use of food side-flows as animal feed shows environmental advantages in all scenarios, as the use of conventional feed, such as soybean meal or hay, is reduced and so are the GHG emissions. The anaerobic digestion of food side-flows is associated with significant GHG emissions, but alternative energy also display a high GHG factor when based on fossil resources. The measuring of circularity in the food sector is a challenge in itself due to the complexity of renewable materials. This study shall help to understand the interwoven influences of certain parameters to the results. © 2020 The Author(s)
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- Schwellnus, F., et al.
(author)
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Study of low work function materials for hot cavity resonance ionization laser ion sources
- 2009
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In: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 267:10, s. 1856-1861
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Journal article (peer-reviewed)abstract
- The selectivity of a hot cavity resonance ionization laser ion source (RILIS) is most often limited by contributions from competing surface ionization of the hot walls of the ionization cavity. In this article we present investigations on the properties of designated high temperature, low work function materials regarding their performance and suitability as cavity material for RILIS. Tungsten test cavities, impregnated with a mixture of barium oxide and strontium oxide (BaOSrO on W), or alternatively gadolinium hexaboride (GdB6) were studied in comparison to a standard tungsten RILIS cavity as being routinely used for hot cavity laser ionization at ISOLDE. Measurement campaigns took place at the off-line mass separators at ISOLDE/CERN, Geneva and RISIKO/University of Mainz.
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- Sebastianutto, Irene, et al.
(author)
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D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson’s disease
- 2020
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In: Journal of Clinical Investigation. - 0021-9738. ; 130:3, s. 1168-1184
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Journal article (peer-reviewed)abstract
- Dopamine receptor D1 modulates glutamatergic transmission in cortico-basal ganglia circuits and represents a major target of L-DOPA therapy in Parkinson’s disease. Here we show that D1 and metabotropic glutamate type 5 (mGlu5) receptors can form previously unknown heteromeric entities with distinctive functional properties. Interacting with Gq proteins, cell-surface D1-mGlu5 heteromers exacerbated PLC signaling and intracellular calcium release in response to either glutamate or dopamine. In rodent models of Parkinson’s disease, D1-mGlu5 nanocomplexes were strongly upregulated in the dopamine-denervated striatum, resulting in a synergistic activation of PLC signaling by D1 and mGlu5 receptor agonists. In turn, D1-mGlu5–dependent PLC signaling was causally linked with excessive activation of extracellular signal–regulated kinases in striatal neurons, leading to dyskinesia in animals treated with L-DOPA or D1 receptor agonists. The discovery of D1-mGlu5 functional heteromers mediating maladaptive molecular and motor responses in the dopamine-denervated striatum may prompt the development of new therapeutic principles for Parkinson’s disease.
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| 15. |
- Shamba, Donat, et al.
(author)
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Barriers and enablers to routine register data collection for newborns and mothers: EN-BIRTH multi-country validation study.
- 2021
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In: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 21:Suppl 1
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Journal article (peer-reviewed)abstract
- Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use.The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018-March 2019): hospital nurse-midwives and doctors who fill ward registers after birth (n = 40 IDI and n = 5 FGD); and data collectors (n = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories.Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users.Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals.
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