Protected urban green spaces (PUGS) are exposed to numerous disturbances and threats since they are immersed in highly dynamic socio-ecological systems. PUGS in highly urbanized cities require ...particular conservation strategies. Here, we propose an approach for PUGS management which integrates three components: i) scientific knowledge (monitoring/restoration), ii) community interaction with the environment, and iii) management decision. Our hypothesis asserts that the intersection of these components should produce a solid management program, provided that the obtained multidisciplinary knowledge meets the needs of information required by the community and decision makers. We tested this hypothesis for a small PUGS located within Mexico City at the National Autonomous University of Mexico campus that holds the Ecological Reserve of Pedregal de San Ángel. Through a participatory approach we built a mental model to understand the perceptions of different campus actors (students, academics and administrators), and their social and ecological relationships with this PUGS. Our findings provide insight into the actors’ perceptions and concerns and suggest that the interactions among the three components, although important, are not self-generated and must be constructed. The findings also suggest that one of the management problems is the mismatch between scientific knowledge and conservation programs. It is paramount to include generated knowledge into management and monitoring programs. The complexity of the PUGS requires an active collaboration among actors and monitoring the development of management strategies using the three components while taking the conservation goals into account.
ABSTRACT
Dysregulated neutrophil extravasation contributes to the pathogenesis of many inflammatory disorders. Pericytes (PCs) have been implicated in the regulation of neutrophil transmigration, and ...previous work demonstrates that endothelial cell (EC)‐derived signals reduce PC barrier function; however, the signaling mechanisms are unknown. Here, we demonstrate a novel role for EC‐derived macrophage migration inhibitory factor (MIF) in inhibiting PC contractility and facilitating neutrophil transmigration. With the use of micro‐ELISAs, RNA sequencing, quantitative PCR, and flow cytometry, we found that ECs secrete MIF, and PCs upregulate CD74 in response to TNF‐α. We demonstrate that EC‐derived MIF decreases PC contractility on 2‐dimensional silicone substrates via reduction of phosphorylated myosin light chain. With the use of an in vitro microvascular model of the human EC–PC barrier, we demonstrate that MIF decreases the PC barrier to human neutrophil transmigration by increasing intercellular PC gap formation. For the first time, an EC‐specific MIF knockout mouse was used to investigate the effects of selective deletion of EC MIF. In a model of acute lung injury, selective deletion of EC MIF decreases neutrophil infiltration to the bronchoalveolar lavage and tissue and simultaneously decreases PC relaxation by increasing myosin light‐chain phosphorylation. We conclude that paracrine signals from EC via MIF decrease PC contraction and enhance PC‐regulated neutrophil transmigration.—Pellowe, A. S., Sauler, M., Hou, Y., Merola, J., Liu, R., Calderon, B., Lauridsen, H. M., Harris, M. R., Leng, L., Zhang, Y., Tilstam, P. V., Pober, J. S., Bucala, R., Lee, P. J., Gonzalez, A. L. Endothelial cell‐secreted MIF reduces pericyte contractility and enhances neutrophil extravasation. FASEB J. 33, 2171–2186 (2019). www.fasebj.org
Targeting different cell surface receptors with nanoparticle (NP)-based platforms can result in differential particle binding properties that may impact their localization, bioavailability, and, ...ultimately, the therapeutic efficacy of an encapsulated payload. Conventional in vitro assays comparing the efficacy of targeted NPs often do not adequately control for these differences in particle–receptor binding, potentially confounding their therapeutic readouts and possibly even limiting their experimental value. In this work, we characterize the conditions under which NPs loaded with Bruton’s Tyrosine Kinase (BTK) inhibitor differentially suppress primary B cell activation when targeting either CD19 (internalizing) or B220 (noninternalizing) surface receptors. Surface binding of fluorescently labeled CD19- and B220-targeted NPs was analyzed and quantitatively correlated with the number of bound particles at given treatment concentrations. Using this binding data, suppression of B cell activation was directly compared for differentially targeted (CD19 vs B220) NPs loaded with a BTK inhibitor at a range of particle drug loading concentrations. When NPs were loaded with lower amounts of drug, CD19-mediated internalization demonstrated increased inhibition of B cell proliferation compared with B220 NPs. However, these differences were mitigated when particles were loaded with higher concentrations of BTK inhibitor and B220-mediated “paracrine-like” delivery demonstrated superior suppression of cellular activation when cells were bound to lower overall numbers of NPs. Taken together, these results demonstrate that inhibition of B cell activation can be optimized for NPs targeting either internalizing or noninternalizing surface receptors and that particle internalization is likely not a requisite endpoint when designing particles for delivery of BTK inhibitor to B cells.
The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Public health strategies to reduce viral transmission are based on ...widespread diagnostic testing to detect and isolate contagious patients. Several reverse transcription (RT)-PCR tests, along with other SARS-CoV-2 diagnostic assays, are available to attempt to cover the global demand. Loop-mediated isothermal amplification (LAMP) based methods have been established as rapid, accurate, point of care diagnostic tests for viral infections; hence, they represent an excellent alternative for SARS-CoV-2 detection. The aim of this study was to develop and describe molecular detection systems for SARS-CoV-2 based on RT-LAMP. Recombinant DNA polymerase from Bacillus stearothermophilus and thermostable engineered reverse transcriptase from Moloney Murine Leukemia Virus were expressed using a prokaryotic system and purified by fast protein liquid chromatography. These enzymes were used to set up fluorometric real time and colorimetric end-point RT-LAMP assays. Several reaction conditions were optimized such as reaction temperature, Tris-HCl concentration, and pH of the diagnostic tests. The key enzymes for RT-LAMP were purified and their enzymatic activity was determined. Standardized reaction conditions for both RT-LAMP assays were 65°C and a Tris-HCl-free buffer at pH 8.8. Colorimetric end-point RT-LAMP assay was successfully used for viral detection from clinical saliva samples with 100% sensitivity and 100% specificity compared to the results obtained by RT-qPCR based diagnostic protocols with Ct values until 30. The developed RT-LAMP diagnostic tests based on purified recombinant enzymes allowed a sensitive and specific detection of the nucleocapsid gene of SARS-CoV-2.
Microalgae as biostimulants: a new approach in agriculture González-Pérez, Brenda Karen; Rivas-Castillo, Andrea Margarita; Valdez-Calderón, Alejandro ...
World journal of microbiology & biotechnology,
01/2022, Letnik:
38, Številka:
1
Journal Article
Recenzirano
This review aims to elucidate the state of the art of microalgae-based biostimulants as a tool in agriculture by summarizing the biologically active compounds factors that influence the use of ...microalgae biostimulants and their application methods in the field. Additionally, we examined the factors that support the use of microalgal biostimulants to face abiotic and biotic stress in crop plants. The use of microalgae in crop production and the benefits of seed preparation, foliar application, soil drenching, and hydroponic treatments were discussed. Furthermore, the use of these biostimulants in crop plants and their multiple benefits such as, better rooting, higher crop, fruit yields, drought and salinity tolerance, photosynthetic activity and pathogen resistance was thoroughly presented. The present situation of microalgal biostimulants and their difficulties in the market was analyzed, as well as the perspectives of their use. However, data shows that microalgal derived biostimulants can be used as an alternative for the protection of crops and plant growth regulators and play a significant key role in increasing the levels of production, yield and health of crops. Special interest needs to focus on investigating more microalgae species and their biological active compound factors, due to the largely untapped field. Perspectives regarding future research lines and development priorities were included.
Endocrine disruptors can alter biological functions in aquatic organisms at low levels. Triclosan, a commonly used active ingredient in personal care products around the world, is frequently detected ...in the environment. Likewise, 4-nonylphenol is used in products such as plastics, personal care products, and cleaning agents. Zooplankton species such as cladocerans are used in acute and chronic ecotoxicological assays.
Daphnia laevis
is a commonly found cladoceran in Mexican water bodies and has been used in previous ecotoxicological experiments. In this work, median effective concentration of triclosan and 4-nonylphenol (EC
50
, 24 h) for immobilization for the cladoceran were derived. Based on the acute toxicity data (368.6 and 200 µg L
−1
, respectively), three sublethal concentrations of both compounds (30, 60, 120 and 10, 20, 40 µg L
−1
, respectively) were used to evaluate population responses. Population growth curves of
D. laevis
were affected significantly, indicating decreases in peak abundances in all treatments (0.5 for triclosan and 1 ind mL
−1
for 4-nonylphenol) compared to controls (2 ind mL
−1
). The effect of the exposition of both endocrine disruptors was significant in the majority of the treatments; however, 4-nonylphenol was more toxic
to D. laevis
, than triclosan. This can be explained through the great number of interactions of binding sites on the amino acid, arginine kinase, contributing to the inhibition of the regulation of cellular energy used in survival and reproductive pathways of the cladoceran.
Cells employ several adaptive mechanisms under conditions of accelerated cell division, such as the unfolded protein response (UPR). The UPR is composed of a tripartite signaling system that involves ...ATF6, PERK, and IRE1, which maintain protein homeostasis (proteostasis). However, deregulation of protein translation initiation could be associated with breast cancer (BC) chemoresistance. Specifically, eukaryotic initiation factor-4A (eIF4A) is involved in the unfolding of the secondary structures of several mRNAs at the 5' untranslated region (5'-UTR), as well as in the regulation of targets involved in chemoresistance. Importantly, the tumor suppressor gene PDCD4 could modulate this process. This regulation might be disrupted in chemoresistant triple negative-BC (TNBC) cells. Therefore, we characterized the effect of doxorubicin (Dox), a commonly used anthracycline medication, on human breast carcinoma MDA-MB-231 cells. Here, we generated and characterized models of Dox chemoresistance, and chemoresistant cells exhibited lower Dox internalization levels followed by alteration of the IRE1 and PERK arms of the UPR and triggering of the antioxidant Nrf2 axis. Critically, chemoresistant cells exhibited PDCD4 downregulation, which coincided with a reduction in eIF4A interaction, suggesting a sophisticated regulation of protein translation. Likewise, Dox-induced chemoresistance was associated with alterations in cellular migration and invasion, which are key cancer hallmarks, coupled with changes in focal adhesion kinase (FAK) activation and secretion of matrix metalloproteinase-9 (MMP-9). Moreover, eIF4A knockdown via siRNA and its overexpression in chemoresistant cells suggested that eIF4A regulates FAK. Pro-atherogenic low-density lipoproteins (LDL) promoted cellular invasion in parental and chemoresistant cells in an MMP-9-dependent manner. Moreover, Dox only inhibited parental cell invasion. Significantly, chemoresistance was modulated by cryptotanshinone (Cry), a natural terpene purified from the roots of
. Cry and Dox co-exposure induced chemosensitization, connected with the Cry effect on eIF4A interaction. We further demonstrated the Cry binding capability on eIF4A and in silico assays suggest Cry inhibition on the RNA-processing domain. Therefore, strategic disruption of protein translation initiation is a druggable pathway by natural compounds during chemoresistance in TNBC. However, plasmatic LDL levels should be closely monitored throughout treatment.
Many bacterial pathogens antagonize host defense responses by translocating effector proteins into cells. It remains an open question how those pathogens not encoding effectors counteract ...anti-bacterial immunity. Here, we show that Klebsiella pneumoniae exploits the evolutionary conserved innate protein SARM1 to regulate negatively MyD88- and TRIF-governed inflammation, and the activation of the MAP kinases ERK and JNK. SARM1 is required for Klebsiella induction of interleukin-10 (IL-10) by fine-tuning the p38-type I interferon (IFN) axis. SARM1 inhibits the activation of Klebsiella-induced absent in melanoma 2 inflammasome to limit IL-1β production, suppressing further inflammation. Klebsiella exploits type I IFNs to induce SARM1 in a capsule and lipopolysaccharide O-polysaccharide-dependent manner via the TLR4-TRAM-TRIF-IRF3-IFNAR1 pathway. Absence of SARM1 reduces the intracellular survival of K. pneumoniae in macrophages, whereas sarm1-deficient mice control the infection. Altogether, our results illustrate an anti-immunology strategy deployed by a human pathogen. SARM1 inhibition will show a beneficial effect to treat Klebsiella infections.
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•SARM1 is an evolutionary conserved innate immune protein with a TIR domain•Klebsiella pneumoniae induces SARM1 to limit inflammation, and to induce IL-10•SARM1 inhibits the action of AIM2 inflammasome to limit IL-1β production•In vivo, absence of SARM1 facilitates the clearance of Klebsiella pneumoniae
Feriotti et al. uncover how Klebsiella pneumoniae exploits the conserved innate immune protein SARM1 to limit inflammation and to induce IL-10. SARM1 also inhibits K. pneumoniae-induced AIM2 inflammasome. In vivo, absence of SARM1 facilitates the clearance of the pathogen, revealing an Achilles heel of our immune system exploited by Klebsiella.
In this review, research on the use of microalgae as an option for bioremediation purposes of pharmaceutical compounds is reported and discussed thoroughly. Pharmaceuticals have been detected in ...water bodies around the world, attracting attention towards the increasing potential risks to humans and aquatic biota. Unfortunately, pharmaceuticals have no regulatory standards for safe disposal in many countries. Despite the advances in new analytical techniques, the current wastewater treatment facilities in many countries are ineffective to remove the whole presence of pharmaceutical compounds and their metabolites. Though new methods are substantially effective, removal rates of drugs from wastewater make the cost-effectiveness ratio a not viable option. Therefore, the necessity for investigating and developing more adequate removal treatments with a higher efficiency rate and at a lower cost is mandatory. The present review highlights the algae-based removal strategies for bioremediation purposes, considering their pathway as well as the removal rate and efficiency of the microalgae species used in assays. We have critically reviewed both application of living and non-living microalgae biomass for bioremediation purposes considering the most commonly used microalgae species. In addition, the use of modified and immobilized microalgae biomass for the removal of pharmaceutical compounds from water was discussed. Furthermore, research considering various microalgal species and their potential use to detoxify organic and inorganic toxic compounds were well evaluated in the review. Further research is required to exploit the potential use of microalgae species as an option for the bioremediation of pharmaceuticals in water.
IntroductionHuman papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of ...cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC.Methods and analysisWomen aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT01881659
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