Heme is an essential prosthetic group in proteins that reside in virtually every subcellular compartment performing diverse biological functions. Irrespective of whether heme is synthesized in the ...mitochondria or imported from the environment, this hydrophobic and potentially toxic metalloporphyrin has to be trafficked across membrane barriers, a concept heretofore poorly understood. Here we show, using subcellular-targeted, genetically encoded hemoprotein peroxidase reporters, that both extracellular and endogenous heme contribute to cellular labile heme and that extracellular heme can be transported and used in toto by hemoproteins in all six subcellular compartments examined. The reporters are robust, show large signal-to-background ratio, and provide sufficient range to detect changes in intracellular labile heme. Restoration of reporter activity by heme is organelle-specific, with the Golgi and endoplasmic reticulum being important sites for both exogenous and endogenous heme trafficking. Expression of peroxidase reporters in Caenorhabditis elegans shows that environmental heme influences labile heme in a tissue-dependent manner; reporter activity in the intestine shows a linear increase compared with muscle or hypodermis, with the lowest heme threshold in neurons. Our results demonstrate that the trafficking pathways for exogenous and endogenous heme are distinct, with intrinsic preference for specific subcellular compartments. We anticipate our results will serve as a heuristic paradigm for more sophisticated studies on heme trafficking in cellular and whole-animal models.
Vultures constitute an important functional group in many ecosystems, providing crucial ecosystem services both in natural and humanized environments. These scavengers are facing massive declines ...worldwide, but in several African countries virtually nothing is known on populations' status and threats, hampering the development of adequate conservation strategies. In Guinea-Bissau, globally important populations of Hooded Necrosyrtes monachus and African white-backed vultures Gyps africanus were recently reported. Using the country as a study area, we aim to characterize human-vulture interactions in West Africa applying a multidisciplinary approach. We assessed the status and distribution of vulture populations using data from 1711 km of roadside transects, examined predictors of their distribution, and produced a nationwide population estimate for the Hooded Vulture, using an innovative method based on the relationship between the size of human population in settlements and vulture numbers. We conducted 47 stakeholder interviews to assess perceived roles played by vultures, and to investigate potential anthropogenic threats. Hooded vultures were strongly associated with high human population densities, whereas no relation was found between African white-backed and Rüppell's vultures and any of the tested predictors, which included cattle density, precipitation and Normalized Difference Vegetation Index, among others. We estimate a national population of 43347 Hooded vultures, the largest population reported in the species range. Respondents were generally aware of the services provided by vultures, especially waste and carcass removal, including in urban areas. Hunting for witchcraft and traditional medicine was the most frequently recognised threat, while poisoning was ranked as having the highest impact. We hypothesise that poisoning-related mortality may be affecting African white-backed and Rüppell's vultures' distribution and explain their scarcity in apparently highly suitable habitats. Our results suggest a mutualistic rather than a commensalistic relationship between vultures and humans, with important implications for designing and implementing conservation strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces ...Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day (p.o.) and corticosterone for 21 days and the daily administrations of experimental drugs were given immediately prior to corticosterone (20 mg/kg/day, p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (−/−)) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle. Twenty-four hours after the last treatments, the behavioral tests and biochemical assays were performed. Agmatine treatment for 21 days was able to abolish the corticosterone-induced depressive-like behavior and the alterations in the immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and glutamate levels. Agmatine also abolished the corticosterone-induced changes in the morphology of astrocytes and microglia in CA1 region of hippocampus. In addition, agmatine treatment in control mice increased noradrenaline, serotonin, and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine’s ability to produce an antidepressant-like effect was abolished in Nrf2 (−/−) mice. The present results reinforce the participation of Nrf2 in the antidepressant-like effect produced by agmatine and expand literature data concerning its mechanisms of action.
Heme is a prosthetic group of proteins involved in vital physiological processes. It participates, for example, in redox reactions crucial for cell metabolism due to the variable oxidation state of ...its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The export of heme initially attributed to the feline leukemia virus C receptor (FLVCR) has recently been called into question, following the discovery of choline uptake by the same receptor in mammals. Here, we found that RpFLVCR is a heme exporter in the midgut of the hematophagous insect Rhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl‐biliverdin, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity, and activated mitochondrial biogenesis, effects not observed in RpHO‐silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.
FLVCR function as heme exporters in the midgut of the hematophagous insect Rhodnius prolixus and play a key role in heme/iron metabolism, mitochondrial biogenesis, and maintenance of redox balance: RpFLVCR‐KD decreases available hemolymphatic heme and increases intracellular levels of dicysteinyl‐biliverdin, the product of the HO reaction, which is overexpressed in this scenario. These results indicate heme retention in midgut cells. Furthermore, RpFLVCR knockdown strongly increased oxidant production and lipid peroxidation and activated mitochondrial biogenesis, effects not observed in RpHO‐silenced insects.
Aedes aegypti is the vector of some of the most important vector-borne diseases like dengue, chikungunya, zika and yellow fever, affecting millions of people worldwide. The cellular processes that ...follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in reactive oxygen species (ROS) production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An integrated understanding of both social and ecological aspects of environmental issues is essential to address pressing sustainability challenges. An integrated social-ecological systems ...perspective is purported to provide a better understanding of the complex relationships between humans and nature. Despite a threefold increase in the amount of social-ecological research published between 2010 and 2015, it is unclear whether these approaches have been truly integrative. We conducted a systematic literature review to investigate the conceptual, methodological, disciplinary, and functional aspects of social-ecological integration. In general, we found that overall integration is still lacking in social-ecological research. Some social variables deemed important for addressing sustainability challenges are underrepresented in social-ecological studies, e.g., culture, politics, and power. Disciplines such as ecology, urban studies, and geography are better integrated than others, e.g., sociology, biology, and public administration. In addition to ecology and urban studies, biodiversity conservation plays a key brokerage role in integrating other disciplines into social-ecological research. Studies founded on systems theory have the highest rates of integration. Highly integrative studies combine different types of tools, involve stakeholders at appropriate stages, and tend to deliver practical recommendations. Better social-ecological integration must underpin sustainability science. To achieve this potential, future social-ecological research will require greater attention to the following: the interdisciplinary composition of project teams, strategic stakeholder involvement, application of multiple tools, incorporation of both social and ecological variables, consideration of bidirectional relationships between variables, and identification of implications and articulation of clear policy recommendations.
The aeronautical and automotive industries have, as an essential objective, the energy efficiency optimization of aircraft and cars, while maintaining stringent functional requirements. One working ...line focuses on the use of lightweight structural materials to replace conventional materials. For this reason, it is considered enlightening to carry out an analysis of the literature published over the last 20 years through Open Access literature. For this purpose, a systematic methodology is applied to minimize the possible risks of bias in literature selection and analysis. Web of Science is used as a search engine. The final selection comprises the 30 articles with the highest average numbers of citations per year published from 2015 to 2020 and the 7 articles published from the period of 2000–2014. Overall, the selection is composed of 37 Open Access articles with 2482 total citations and an average of 67.1 citations per article/year published, and includes Q1 (62%) and Q2 (8%) articles and proceeding papers (30%). The study seeks to inform about the current trends in materials and processes in lightweight structural materials for aeronautical and automotive applications with a sustainable perspective. All the information collected is summarized in tables to facilitate searches and interpretation by interested researchers.
Yolk biogenesis and consumption have been well conserved in oviparous animals throughout evolution. Most egg-laying animals store yolk proteins within the oocytes' yolk granules (Ygs). Following ...fertilization, the Ygs participate in controlled pathways of yolk breakdown to support the developing embryo's anabolic metabolism. While the unfolding of the yolk degradation program is a crucial process for successful development in many species, the molecular mechanisms responsible for yolk mobilization are still mysterious and have mostly not been explored. Here, we investigate the functional role of the oocyte maternally accumulated mRNAs of a protein phosphatase (PP501) and two aspartic proteases (cathepsin-D 405, CD405 and cathepsin-D 352, CD352) in the yolk degradation and reproduction of the insect vector of Chagas disease
. We found that PP501 and CD352 are highly expressed in the vitellogenic ovary when compared to the other organs of the adult insect. Parental RNAi silencing of PP501 resulted in a drastic reduction in oviposition and increased embryo lethality whereas the silencing of CD352 resulted only in a slight decrease in oviposition and embryo viability. To further investigate the PP501-caused high reproduction impairment, we investigated the Ygs biogenesis during oocyte maturation and the activation of the yolk degradation program at early development. We found that the Ygs biogenesis was deficient during oogenesis, as seen by flow cytometry, and that, although the PP501-silenced unviable eggs were fertilized, the Ygs acidification and acid phosphatase activity were affected, culminating in a full impairment of the yolk proteins degradation at early embryogenesis. Altogether we found that PP501 is required for the oocyte maturation and the activation of the yolk degradation, being, therefore, essential for this vector reproduction.
Vector-borne diseases are globally prevalent and represent a major socioeconomic problem worldwide. Blood-sucking arthropods transmit most pathogenic agents that cause these human infections. The ...pathogens transmission to their vertebrate hosts depends on how efficiently they infect their vector, which is particularly impacted by the microbiota residing in the intestinal lumen, as well as its cells or internal organs such as ovaries. The balance between costs and benefits provided by these interactions ultimately determines the outcome of the relationship. Here, we will explore aspects concerning the nature of microbe–vector interactions, including the adaptive traits required for their establishment, the varied outcomes of symbiotic interactions, as well as the factors influencing the transition of these relationships across a continuum from parasitism to mutualism.
•Vector–symbiont bond is dynamic and transit along parasitism and mutualism continuum.•Environmental and genetic changes influence the vector–symbiont relationship continuum.•The balance between gains and adaptative costs shapes host–symbiont interactions.•Host resistance and tolerance tune vector–parasite interaction costs.
Negative interactions between humans and venomous snakes are increasing, with the World Health Organization committed to halving snakebite deaths and disabilities by 2030. Evidence‐based strategies ...are thus urgently required to reduce snakebite events in high‐risk areas, while promoting snake conservation. Understanding the factors that drive the adoption of snakebite prevention measures is critical for the effective implementation of snakebite management strategies. We conducted in‐person questionnaires (n = 535 respondents) with rural agricultural communities within the Thiruvarur District of Tamil Nadu, India, a national snakebite hotspot. Using a health belief model framework, we explored current snakebite prevention measures and factors impacting their adoption. The majority of respondents reported using multiple snakebite prevention measures. Perceived self‐efficacy and perceived risk frequency of snakebites were important overall predictors of future adoption, whereas education, gender, relative wealth, and current adoption were important for specific measures. Achieving international commitments to support human–snake coexistence will require collective and collaborative action (e.g., governments, donor agencies, civil society organizations, researchers, and communities) underpinned by behavioural insights and context‐specific solutions.
The study investigates strategies for reducing negative interactions between humans and venomous snakes. Using a health belief model framework, the research examines factors influencing the adoption of snakebite prevention measures in a high snakebite‐risk area of southern India. The findings emphasize the importance of factors like perceived self‐efficacy and perceived risk frequency in shaping the uptake of such measures, highlighting the need for collaborative efforts and context‐specific solutions to achieve more harmonious coexistence between humans and snakes.
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