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1.
Cells ; 13(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38994982

RESUMO

There has been a significant increase in the consumption of cannabis for both recreational and medicinal purposes in recent years, and its use can have long-term consequences on cognitive functions, including memory. Here, we review the immediate and long-term effects of cannabis and its derivatives on glutamatergic neurotransmission, with a focus on both the presynaptic and postsynaptic alterations. Several factors can influence cannabinoid-mediated changes in glutamatergic neurotransmission, including dosage, sex, age, and frequency of use. Acute exposure to cannabis typically inhibits glutamate release, whereas chronic use tends to increase glutamate release. Conversely, the postsynaptic alterations are more complicated than the presynaptic effects, as cannabis can affect the glutamate receptor expression and the downstream signaling of glutamate. All these effects ultimately influence cognitive functions, particularly memory. This review will cover the current research on glutamate-cannabis interactions, as well as the future directions of research needed to understand cannabis-related health effects and neurological and psychological aspects of cannabis use.


Assuntos
Canabinoides , Cannabis , Ácido Glutâmico , Transmissão Sináptica , Humanos , Transmissão Sináptica/efeitos dos fármacos , Canabinoides/farmacologia , Canabinoides/metabolismo , Ácido Glutâmico/metabolismo , Cannabis/metabolismo , Animais
2.
Artigo em Inglês | MEDLINE | ID: mdl-39048405

RESUMO

The clinical landscape for endometrial cancer in the UK is evolving to include new management guidelines and targeted treatment options. An understanding of current treatment and management practices in the UK will help services plan and adapt to upcoming changes. AIM: The purpose of this survey was to understand current and anticipated real-world practices for endometrial cancer care in the UK and potential areas for optimisation. MATERIALS AND METHODS: Telephone interviews were conducted in November/December 2021 with UK-based healthcare professionals involved in endometrial cancer management. Questions were aligned with the British Gynaecological Cancer Society/European Society for Medical Oncology recommendations, covering the pathway from diagnosis and treatment to follow-up. RESULTS: A total of 63 healthcare professionals (HCPs) involved in the management of patients with endometrial cancer participated in telephone interviews. The results highlighted variations in management and treatment practices for endometrial cancer and suggest that current UK practice appears to diverge from national and international guidance in some instances. While somatic mismatch repair deficiency testing was used by 89.7% of respondents as mainstream testing, the survey highlighted a lack of access to other key molecular biomarker tests, such as polymerase epsilon (POLE) sequencing (used by only 9.8% of HCPs at the time of the survey). CONCLUSION: The results highlighted several perceived practical barriers to the swift adoption of new therapeutic options, including funding access, limited staff, treatment-related resources, staff education, and support. Our findings support the need for better access to biomarkers that could enable more effective and targeted treatments.

3.
Gene Protein Dis ; 3(1)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38766604

RESUMO

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

4.
Ann R Coll Surg Engl ; 106(4): 321-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38555869

RESUMO

Genomics is a crucial part of managing surgical disease. This review focuses on some of the genomic advances that are available now and looks to the future of their application in surgical practice. Whole-genome sequencing enables unbiased coverage across the entire human genome of approximately three billion base pairs. Newer technologies, such as those that permit long-read sequence analysis, provide additional information in longer phased fragment and base pair epigenomic (methylomic) data. Whole-genome sequencing is currently available in England for cancers in children, teenagers and young adults, central nervous system tumours, sarcoma and haematological malignancies. Circulating tumour DNA (ctDNA), immunotherapy and pharmacogenomics have emerged as groundbreaking approaches in the field of cancer treatment. These are now revolutionising the way oncologists and surgeons approach curative cancer surgery. Cancer vaccines offer an innovative approach to reducing recurrence after surgery by priming the immune system to trigger an immune response. The Cancer Vaccine Launch Pad project facilitates cancer vaccine studies in England. The BNT122-01 trial is recruiting patients with ctDNA-positive high-risk colorectal cancer after surgery to assess the impact of cancer vaccines. The evolving landscape of cancer treatment demands a dynamic and integrated approach from the surgical multidisciplinary team. Immunotherapy, ctDNA, pharmacogenomics, vaccines, mainstreaming and whole-genome sequencing are just some of the innovations that have the potential to redefine the standards of care. The continued exploration of these innovative diagnostics and therapies, the genomic pathway evolution and their application in diverse cancer types highlights the transformative impact of precision medicine in surgery.


Assuntos
Vacinas Anticâncer , DNA Tumoral Circulante , Neoplasias , Cirurgiões , Criança , Humanos , Adolescente , DNA Tumoral Circulante/genética , Genômica
5.
Front Mol Biosci ; 10: 1160851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37577751

RESUMO

Background: Tissue fibrosis is a major healthcare burden that affects various organs in the body for which no effective treatments exist. An underlying, emerging theme across organs and tissue types at early stages of fibrosis is the activation of pericytes and/or fibroblasts in the perivascular space. In hepatic tissue, it is well known that liver sinusoidal endothelial cells (EC) help maintain the quiescence of stellate cells, but whether this phenomenon holds true for other endothelial and perivascular cell types is not well studied. Methods: The goal of this work was to develop an organ-on-chip microvascular model to study the effect of EC co-culture on the activation of perivascular cells perturbed by the pro-fibrotic factor TGFß1. A high-throughput microfluidic platform, PREDICT96, that was capable of imparting physiologically relevant fluid shear stress on the cultured endothelium was utilized. Results: We first studied the activation response of several perivascular cell types and selected a cell source, human dermal fibroblasts, that exhibited medium-level activation in response to TGFß1. We also demonstrated that the PREDICT96 high flow pump triggered changes in select shear-responsive factors in human EC. We then found that the activation response of fibroblasts was significantly blunted in co-culture with EC compared to fibroblast mono-cultures. Subsequent studies with conditioned media demonstrated that EC-secreted factors play at least a partial role in suppressing the activation response. A Luminex panel and single cell RNA-sequencing study provided additional insight into potential EC-derived factors that could influence fibroblast activation. Conclusion: Overall, our findings showed that EC can reduce myofibroblast activation of perivascular cells in response to TGFß1. Further exploration of EC-derived factors as potential therapeutic targets in fibrosis is warranted.

6.
J Insect Sci ; 23(4)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37428828

RESUMO

Flight mills are widely used to investigate insect flight behavior. As technology advances, the means to build a computerized control system for a flight mill has become more accessible in terms of both price and availability of components. However, the specialized electronics and programming knowledge required to build such a system can still present an obstacle to interested parties. Here, we describe a simple and inexpensive flight mill control system that can be easily assembled and operated without specialized experience. The hardware and software components are built around an Arduino single-board microcontroller, which outputs raw data in the form of timestamped detections of rotations of the flight mill arm. This control system is suitable both as the basis for new flight mills and for replacing outdated computer controls on existing flight mills. Additionally, it can be used with any rotary flight mill design that uses an electronic sensor to count rotations.


Assuntos
Voo Animal , Insetos , Animais
7.
Aquat Toxicol ; 260: 106584, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37267806

RESUMO

Estrogenic endocrine disrupting chemicals (EEDC) have been suspected to impact offspring in a transgenerational manner via modifications of the germline epigenome in the directly exposed generations. A holistic assessment of the concentration/ exposure duration-response, threshold level, and critical exposure windows (parental gametogenesis and embryogenesis) for the transgenerational evaluation of reproduction and immune compromise concomitantly will inform the overall EEDC exposure risk. We conducted a multigenerational study using the environmental estrogen, 17α-ethinylestradiol (EE2), and the marine laboratory model fish Oryzias melastigma (adult, F0) and their offspring (F1-F4) to identify transgenerationally altered offspring generations and phenotype persistence. Three exposure scenarios were used: short parental exposure, long parental exposure, and a combined parental and embryonic exposure using two concentrations of EE2 (33ng/L, 113ng/L). The reproductive fitness of fish was evaluated by assessing fecundity, fertilization rate, hatching success, and sex ratio. Immune competence was assessed in adults via a host-resistance assay. EE2 exposure during both parental gametogenesis and embryogenesis was found to induce concentration/ exposure duration-dependent transgenerational reproductive effects in the unexposed F4 offspring. Furthermore, embryonic exposure to 113 ng/L EE2 induced feminization of the directly exposed F1 generation, followed by subsequent masculinization of the F2 and F3 generations. A sex difference was found in the transgenerationally impaired reproductive output with F4 females being sensitive to the lowest concentration of EE2 (33 ng/L) upon long-term ancestral parent exposure (21 days). Conversely, F4 males were affected by ancestral embryonic EE2 exposure. No definitive transgenerational impacts on immune competence were identified in male or female offspring. In combination, these results indicate that EEDCs can be transgenerational toxicants that may negatively impact the reproductive success and population sustainability of fish populations.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Feminino , Masculino , Oryzias/fisiologia , Aptidão Genética , Poluentes Químicos da Água/toxicidade , Reprodução , Fertilidade , Etinilestradiol/toxicidade
8.
Polit Behav ; : 1-21, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36743232

RESUMO

Americans of all political stripes abstractly support most of the rights and liberties guaranteed by the U.S. Constitution, such as free expression. Yet, we argue that attitudes regarding the basic mechanics of civil liberties-e.g., from whom they are protections-are divided across partisan lines. Because of elite rhetoric, we hypothesize that Republicans are more likely than Democrats to perceive rights violations, often by non-government entities (generally incapable of violations), and that they will perceive rights as under threat with greater frequency. Using a survey containing unique questions about rights, we first demonstrate that a large majority of the mass public has fixed preference structures regarding rights, suggesting that attitudes about liberties are not merely error-ridden, top-of-the-head assessments. These preference structures differ for Democrats and Republicans. Next, we find support for our theory that attitudes regarding rights, from whom they are protective, and their level of protectiveness are asymmetric across partisanship. Beyond implications for citizens' democratic capacities, our results also highlight potential concerns about the influence of partisan bias in demands on leaders regarding rights protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-023-09860-3.

9.
Phytopathology ; 113(6): 998-1009, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36596212

RESUMO

Succinate dehydrogenase inhibitors (SDHIs) are keystone synthetic fungicides used to manage Botrytis cinerea in several hosts. In this study, we investigated the cross-resistance between five new SDHIs (pyraziflumid, isofetamid, benzovindiflupyr, fluxapyroxad, and pydiflumetofen) with commonly used SDHIs boscalid and fluopyram. Different mutations were detected in the sdhB gene in B. cinerea collected from Michigan grapes, and their frequency and EC50 value were determined. Among 216 B. cinerea boscalid-resistant isolates, five different mutations were detected, including H272R/Y, P225F/H, and N230I, at frequencies of 82.6, 4.3, 11.5, 0.4, and 5.3%, respectively. Five isolates of each genotype were used to screen the cross-resistance of the SDHIs. We classified the resistance profile of our mutants into five patterns. We report that all tested mutants were sensitive to benzovindiflupyr, indicating that it can be used as an effective fungicide against all B. cinerea mutants identified in this study. In addition, fluopyram, pydiflumetofen, and isofetamid can provide effective control according to which type of mutation is present in the field. We also developed and compared two molecular diagnostic tools, rhAMP and TaqMan assays, for rapid detection of SDHI resistance-associated mutants in B. cinerea. We report that the TaqMan assay was more successful than the rhAMP assay in detecting the B. cinerea mutant DNA at ≤10 pg and in a single assay was capable of monitoring two amino acid positions. Our results provide essential information about new SDHIs and provide molecular tools for monitoring SDHI resistance mutations, which will assist in gray mold disease control.


Assuntos
Fungicidas Industriais , Succinato Desidrogenase , Succinato Desidrogenase/genética , Succinato Desidrogenase/farmacologia , Patologia Molecular , Doenças das Plantas , Fungicidas Industriais/farmacologia , Botrytis/genética , Niacinamida/farmacologia , Farmacorresistência Fúngica/genética
10.
Phytopathology ; 113(1): 80-89, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35918851

RESUMO

Since its reemergence in 2004, Pseudoperonospora cubensis, the causal agent of cucurbit downy mildew (CDM), has experienced significant changes in fungicide sensitivity. Presently, frequent fungicide applications are required to control the disease in cucumber due to the loss of host resistance. Carboxylic acid amides (CAA) and quinone outside inhibitors (QoI) are two fungicide groups used to control foliar diseases in cucurbits, including CDM. Resistance to these fungicides is associated with single nucleotide polymorphism (SNP) mutations. In this study, we used population analyses to determine the occurrence of fungicide resistance mutations to CAA and QoI fungicides in host-adapted clade 1 and clade 2 P. cubensis isolates. Our results revealed that CAA-resistant genotypes occurred more prominently in clade 2 isolates, with more sensitive genotypes observed in clade 1 isolates, while QoI resistance was widespread across isolates from both clades. We also determined that wild cucurbits can serve as reservoirs for P. cubensis isolates containing fungicide resistance alleles. Finally, we report that the G1105W substitution associated with CAA resistance was more prominent within clade 2 P. cubensis isolates while the G1105V resistance substitution and sensitivity genotypes were more prominent in clade 1 isolates. Our findings of clade-specific occurrence of fungicide resistance mutations highlight the importance of understanding the population dynamics of P. cubensis clades by crop and region to design effective fungicide programs and establish accurate baseline sensitivity to active ingredients in P. cubensis populations.


Assuntos
Fungicidas Industriais , Oomicetos , Peronospora , Fungicidas Industriais/farmacologia , Amidas/farmacologia , Ácidos Carboxílicos/farmacologia , Doenças das Plantas , Oomicetos/genética , Mutação , Estrobilurinas/farmacologia , Quinonas/farmacologia
11.
BMC Biol ; 20(1): 262, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36447225

RESUMO

BACKGROUND: During range expansion in spatially distributed habitats, organisms differ from one another in terms of their patterns of localization versus propagation. To exploit locations or explore the landscape? This is the competition-colonization trade-off, a dichotomy at the core of ecological succession. In bacterial communities, this trade-off is a fundamental mechanism towards understanding spatio-temporal fluxes in microbiome composition. RESULTS: Using microfluidics devices as structured bacterial habitats, we show that, in a synthetic two-species community of motile strains, Escherichia coli is a fugitive species, whereas Pseudomonas aeruginosa is a slower colonizer but superior competitor. We provide evidence highlighting the role of succession and the relevance of this trade-off in the community assembly of bacteria in spatially distributed patchy landscapes. Furthermore, aggregation-dependent priority effects enhance coexistence which is not possible in well-mixed environments. CONCLUSIONS: Our findings underscore the interplay between micron-scale landscape structure and dispersal in shaping biodiversity patterns in microbial ecosystems. Understanding this interplay is key to unleash the technological revolution of microbiome applications.


Assuntos
Infecções por Escherichia coli , Microbiota , Humanos , Biodiversidade , Escherichia coli , Pseudomonas aeruginosa
12.
Front Microbiol ; 13: 831790, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464924

RESUMO

Understanding mechanisms shaping distributions and interactions of soil microbes is essential for determining their impact on large scale ecosystem services, such as carbon sequestration, climate regulation, waste decomposition, and nutrient cycling. As the functional unit of soil ecosystems, we focus our attention on the spatial structure of soil macroaggregates. Emulating this complex physico-chemical environment as a patchy habitat landscape we investigate on-chip the effect of changing the connectivity features of this landscape as Escherichia coli forms a metapopulation. We analyze the distributions of E. coli occupancy using Taylor's law, an empirical law in ecology which asserts that the fluctuations in populations is a power law function of the mean. We provide experimental evidence that bacterial metapopulations in patchy habitat landscapes on microchips follow this law. Furthermore, we find that increased variance of patch-corridor connectivity leads to a qualitative transition in the fluctuation scaling. We discuss these results in the context of the spatial ecology of microbes in soil.

13.
Front Microbiol ; 13: 820738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35391738

RESUMO

Spatiotemporal structures and heterogeneities are common in natural habitats, yet their role in the evolution of antibiotic resistance is still to be uncovered. We applied a microfluidic gradient generator device to study the emergence of resistant bacteria in spatial ciprofloxacin gradients. We observed biofilm formation in regions with sub-inhibitory concentrations of antibiotics, which quickly expanded into the high antibiotic regions. In the absence of an explicit structure of the habitat, this multicellular formation led to a spatial structure of the population with local competition and limited migration. Therefore, such structures can function as amplifiers of selection and aid the spread of beneficial mutations. We found that the physical environment itself induces stress-related mutations that later prove beneficial when cells are exposed to antibiotics. This shift in function suggests that exaptation occurs in such experimental scenarios. The above two processes pave the way for the subsequent emergence of highly resistant specific mutations.

14.
Polit Behav ; 44(2): 937-960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35001995

RESUMO

What explains popular support for political violence in the contemporary United States, particularly the anti-institutional mob that attacked the U.S. Capitol in January 2021? Recent scholarship gives reason to suspect that a constellation of beliefs known as "Christian nationalism" may be associated with support for such violence. We build on this work, arguing that religious ideologies like Christian nationalism should be associated with support for violence, conditional on several individual characteristics that can be inflamed by elite cues. We turn to three such factors long-studied by scholars of political violence: perceived victimhood, reinforcing racial and religious identities, and support for conspiratorial information sources. Each can be exacerbated by elite cues, thus translating individual beliefs in Christian nationalism into support for political violence. We test this approach with original survey data collected in the wake of the Capitol attacks. We find that all the identified factors are positively related to each other and support for the Capitol riot; moreover, the relationship between Christian nationalism and support for political violence is sharply conditioned by white identity, perceived victimhood, and support for the QAnon movement. These results suggest that religion's role in contemporary right-wing violence is embedded with non-religious factors that deserve further scholarly attention in making sense of support for political violence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11109-021-09758-y.

15.
Polit Behav ; 44(4): 1583-1609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33424069

RESUMO

Despite growing recognition among journalists and political pundits, the concept of victimhood has been largely ignored in empirical social science research. In this article, we develop a theory about, and use unique nationally-representative survey data to estimate, two manifestations of victimhood: an egocentric one entailing only perceptions of one's own victimhood, and one focused on blaming "the system." We find that these manifestations of victimhood cut across partisan, ideological, and sociodemographic lines, suggesting that feelings of victimhood are confined to neither "actual" victims nor those partisans on the losing side of elections. Moreover, both manifestations of victimhood, while related to candidate support and various racial attitudes, prove to be distinct from related psychological constructs, such as (collective) narcissism, system justification, and relative deprivation. Finally, an experiment based on candidate rhetoric demonstrates that some political messaging can make supporters feel like victims, which has consequences for subsequent attitudes and behavior.

16.
J Insect Sci ; 21(6)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34918111

RESUMO

We examined the feasibility of externally marking insects with the liquid fluorescent forensic theft deterrent, SmartWater (SmartWater CSI, LLC.). We sprayed captive Lygus hesperus (Knight) (Hemiptera: Miridae), Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), and Hippodamia convergens Guérin-Méneville (Coleoptera: Coccinellidae) with SmartWater fluorophore, and then qualitatively examined them for fluorescence by visual inspection under ultraviolet (UV) light and quantitatively measured them with a multiwavelength microplate fluorometer. The results indicate that this product has enormous potential as a taggant for L. hesperus and B. tabaci. However, the marking efficiency for H. convergens was only adequate. The advantages and limitations of using SmartWater as a biological marker for arthropod mark-release-recapture research are discussed.


Assuntos
Sistemas de Identificação Animal , Artrópodes , Corantes Fluorescentes , Animais
17.
J Am Heart Assoc ; 10(18): e021511, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34514847

RESUMO

Background The loss of endothelial integrity increases the risk of intracerebral hemorrhage during ischemic stroke. Adjunct therapeutic targets for reperfusion in ischemic stroke are in need to prevent blood-brain barrier disruption. Recently, we have shown that endothelial permeability is mediated by lysophosphatidic acid (LPA), but the role of autotaxin, which produces LPA, remains unclear in stroke. We investigate whether autotaxin/LPA axis regulates blood-brain barrier integrity after cerebral ischemia. Methods and Results Ischemic stroke was induced in mice by middle cerebral artery occlusion for 90 minutes, followed by 24-hour reperfusion. The therapeutic efficacy of autotaxin/LPA receptor blockade was evaluated using triphenyl tetrazolium chloride staining, Evans blue permeability, infrared imaging, mass spectrometry, and XF24 analyzer to evaluate blood-brain barrier integrity, autotaxin activity, and mitochondrial bioenergetics. In our mouse model of ischemic stroke, the mRNA levels of autotaxin were elevated 1.7-fold following the cerebral ischemia and reperfusion (I/R) group compared with the sham. The enzymatic activity of autotaxin was augmented by 4-fold in the I/R group compared with the sham. Plasma and brain tissues in I/R group showed elevated LPA levels. The I/R group also demonstrated mitochondrial dysfunction, as evidenced by decreased (P<0.01) basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity. Treatment with autotaxin inhibitors (HA130 or PF8380) or autotaxin/LPA receptor inhibitor (BrP-LPA) rescued endothelial permeability and mitochondrial dysfunction in I/R group. Conclusions Autotaxin-LPA signaling blockade attenuates blood-brain barrier disruption and mitochondrial function following I/R, suggesting targeting this axis could be a new therapeutic approach toward treating ischemic stroke.


Assuntos
Barreira Hematoencefálica/fisiopatologia , Isquemia Encefálica , AVC Isquêmico , Lisofosfolipídeos/metabolismo , Mitocôndrias/patologia , Diester Fosfórico Hidrolases/metabolismo , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , Camundongos , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores
18.
Sci Rep ; 11(1): 12225, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108507

RESUMO

Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.


Assuntos
Comunicação Celular , Técnicas de Cocultura/métodos , Derme/metabolismo , Endotélio Vascular/metabolismo , Técnicas Analíticas Microfluídicas/métodos , Pericitos/metabolismo , Retina/metabolismo , Permeabilidade da Membrana Celular , Células Cultivadas , Derme/citologia , Endotélio Vascular/citologia , Humanos , Pericitos/citologia , Retina/citologia
19.
J Insect Sci ; 21(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33638986

RESUMO

Vernonia [Vernonia galamensis (Cass.) Less.] (Asterales: Asteraceae) was examined as a potential trap crop for the cotton (Gossypium hirsutum L., Malvales: Malvaceae) arthropod complex. Four rows of vernonia were embedded within a 96-row cotton field. The abundance of true bug pests, true bug predators, and spiders were determined by whole-plant and sweep net sampling procedures during the early, middle, and late phases of the cotton-growing season. The census data showed that the arthropods had a strong preference for the vernonia trap crop throughout the cotton-growing season. The movement of the arthropods from the trap crop into cotton was also measured using the protein immunomarking technique as a mark-capture procedure. The arthropods inhabiting the vernonia trap crop were marked directly in the field with a broadcast spray application of egg albumin (protein) during each phase of the study. In turn, the captured specimens were examined for the presence of the mark by an egg albumin-specific enzyme-linked immunosorbent assay. Very few marked specimens were captured beyond the vernonia trap crop 1, 3, and 6 d after each marking event. The arthropods' strong attraction and fidelity to vernonia indicate that it could serve as a trap crop for cotton pests and a refuge for natural enemies.


Assuntos
Distribuição Animal , Controle de Insetos/métodos , Insetos/fisiologia , Características de História de Vida , Aranhas/fisiologia , Vernonia , Animais , Arizona , Produção Agrícola , Gossypium/crescimento & desenvolvimento , Vernonia/crescimento & desenvolvimento
20.
Plant Dis ; 105(2): 285-294, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32762329

RESUMO

Botrytis cinerea on grapes causes bunch rot at both pre- and postharvest stages, in which losses can reach up to 100%. Chemical control primarily relies on the prophylactic use of site-specific fungicides. Repeated applications of these products raise the risk of fungicide resistance development in B. cinerea populations, which can result in disease control failures. To determine the extent of resistance, B. cinerea isolates were collected from grape clusters in the northwest and southwest grape growing regions of Michigan in 2014 and 2018 (n = 115 and 125, respectively). These isolates were phenotyped using discriminatory doses of eight fungicides to determine the levels of resistance. Fungicide resistance increased from 2014 to 2018, mostly affecting the active ingredients fenhexamid, fluopyram, and iprodione. B. cinerea isolates resistant to multiple fungicides were detected in 2014 and 2018, with a higher frequency of resistance in 2018. TaqMan real-time PCR has been developed to detect B. cinerea fungicide resistance to fenhexamid and to differentiate the erg27 F412S/I/V alleles. The TaqMan assay was tested for sensitivity, specificity, and reproducibility on purified DNA and infected grape tissue samples. Our data provide essential information to growers about the efficacy for B. cinerea control using the available botryticides. Furthermore, the developed fenhexamid markers will be transferred to diagnostic clinics to assist growers in the management of bunch rot before resistance-related control failures occur.


Assuntos
Botrytis , Fungicidas Industriais , Amidas , Botrytis/genética , Farmacorresistência Fúngica/genética , Fazendas , Fungicidas Industriais/farmacologia , Michigan , Doenças das Plantas , Reprodutibilidade dos Testes
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