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1.
Ann Ist Super Sanita ; 60(2): 85-88, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984621

RESUMO

The "Investigating and translating genomic evidence for public health response to SARS-CoV-2 (INSIDE SARS-CoV-2)" project is part of the initiative "Joint science and technology cooperation call for joint project proposals for the years 2021-2023" promoted by the Italian Ministry of Foreign Affairs and International Cooperation (MAECI) and the Republic of India. To start the project activities, the pandemic response and the epidemiological situation in Italy and in India, together with the genomic surveillance strategies for SARS-CoV-2 virus in the two countries, are here described.


Assuntos
COVID-19 , Genômica , Saúde Pública , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Itália/epidemiologia , SARS-CoV-2/genética , Índia/epidemiologia , Pandemias , Cooperação Internacional , Genoma Viral
2.
Plant Cell Environ ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011992

RESUMO

Over the last decade, a large effort has been made to understand how extreme climate events disrupt species interactions. Yet, it is unclear how these events affect plants and herbivores directly, via metabolic changes, and indirectly, via their subsequent altered interaction. We exposed common milkweed (Asclepias syriaca) and monarch caterpillars (Danaus plexippus) to control (26:14°C, day:night) or heat wave (HW) conditions (36:24°C, day:night) for 4 days and then moved each organism to a new control or HW partner to disentangle the direct and indirect effects of heat exposure on each organism. We found that the HW directly benefited plants in terms of growth and defence expression (increased latex exudation and total cardenolides) and insect her'bivores through faster larval development. Conversely, indirect HW effects caused both plant latex and total cardenolides to decrease after subsequent herbivory. Nonetheless, increasing trends of more toxic cardenolides and lower leaf nutritional quality after herbivory by HW caterpillars likely led to reduced plant damage compared to controls. Our findings reveal that indirect impacts of HWs may play a greater role in shaping plant-herbivore interactions via changes in key physiological traits, providing valuable understanding of how ecological interactions may proceed in a changing world.

3.
Physiol Rep ; 12(9): e16032, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720166

RESUMO

INPP4A has been shown to be involved in the regulation of cell proliferation and apoptosis of multiple cell types including fibroblasts. Previous reports from our group have demonstrated the role of inositol polyphosphate 4-phosphatase Type I A (INPP4A) in these functions. Though existing evidences suggest a critical role for INPP4A in the maintenance of lung homeostasis, its role in chronic lung diseases is relatively under explored. In the current study, we made an attempt to understand the regulation of INPP4A in idiopathic pulmonary fibrosis (IPF). Through integration of relevant INPP4A gene expression data from public repositories with our results from in vitro experiments and mouse models, we show that INPP4A is altered in IPF. Interestingly, the direction of the change is dependent both on the disease stage and the region of the lung used. INPP4A was found to be upregulated when analyzed in lung sample representative of the whole lung, but was downregulated in the fibrotic regions of the lung. Similarly, INPP4A was found to be high, compared to controls, only in the early stage of the disease. Though the observed increase in INPP4A was found to be negatively correlated to physiological indices, FVC, and DLCO, of lung function, treatment with anti-INPP4A antibody worsened the condition in bleomycin treated mice. These contrasting results taken together are suggestive of a nuanced regulation of INPP4A in IPF which is dependent on the disease stage, cellular state and extent of fibrosis in the lung region being analyzed.


Assuntos
Fibrose Pulmonar Idiopática , Monoéster Fosfórico Hidrolases , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/genética , Animais , Humanos , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Camundongos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Fibroblastos/metabolismo , Feminino
4.
CEN Case Rep ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517598

RESUMO

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is an exceedingly rare cause of glomerulonephritis among children for which prognosis is generally poor, with low incidence of remission and high rates of recurrence after transplant. While there are more cases reported in the adult literature, substantial differences in pediatric vs. adult PGNMID render it essential that we further characterize pediatric cases to optimize management. We report the case of a 12-year-old male presenting initially with edema and hypertension who was subsequently diagnosed with IgG3/Kappa-dominant PGNMID. In the absence of any proven therapy and though without a detectable clone, he was empirically treated with daratumumab with positive effect to date. This is the first reported case of daratumumab monotherapy in pediatric PGNMID, as well as the first PGNMID case to detect presence of C3 nephritic factor.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38509676

RESUMO

BACKGROUND: Nowadays, acidity is a severe problem worldwide caused by excessive gastric acid secretion by the stomach and proximal intestine. OBJECTIVE: Antacids are drugs capable of buffering stomach acid. Therefore, in our research work, we have reported the in-silico studies, synthesis, characterization, and evaluation of antacid activities of magnesium (II) complexes via the acid-base neutralization process. METHODS: In this research, some magnesium complexes were synthesized and their antacid behavior was compared with marketed products. Also, in-silico studies were performed on H+/K+ ATPase (Proton pump). All synthesized compounds were characterized by various spectroscopic techniques like UV-Vis, FT-IR, XRD, and DSC techniques. RESULT: Spectroscopic analysis results showed that the semicarbazone ligand shows keto-enol isomerism and forms a coordinated stable complex with magnesium ions in the crystalline phase. The FT-IR results confirmed the presence of Mg-O stretching, N-H bending, and C=N stretching vibrations in Mg (II) complexes. CONCLUSION: The antacid activities of Mg (II) complexes were excellent as compared to the semicarbazone ligand and comparable with that of marketed antacid drugs like ENO, and Pantop-D. Insilco studies also confirmed that semicarbazone ligand and its Mg (II) complexes were both found to be fitted into the active sites of molecular targets, and Mg (II) complexes showed better binding affinities towards macromolecular as compared to semicarbazone ligand.

6.
Pediatr Blood Cancer ; 71(4): e30890, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38302828

RESUMO

BACKGROUND: Families experience financial burden and household material hardship (HMH) after a pediatric cancer diagnosis. This study investigates types of financial assistance and other financial coping strategies (FCS) adopted by families during the first year after diagnosis. METHODS: Retrospective survey of caregivers of pediatric patients diagnosed with cancer from 2015 to 2019. The survey collected data on demographics, diagnosis, income, HMH, and private, hospital, and government assistance received and other FCS adopted after diagnosis. Bivariate and multivariable logistic regressions were used to analyze FCS by income. Subgroup analysis of families experiencing HMH was used to identify predictors of receiving government assistance. RESULTS: Of 156 respondents, 52% were low-to-middle income, 29% had public insurance, and 22% had non-English language preference. Low-to-middle-income families were more likely to incur debt (odds ratio [OR] 6.24, p < .001) and reduce consumption (OR 2.16, p = .03) than high-income families, and this association persisted in multivariable analysis. Among families with housing, food, and energy insecurity, 40%, 70%, and 39%, respectively, received hospital or government assistance specific to the experienced hardship. In subgroup analysis of families with HMH, after adjusting for income and other confounders, non-English language preference was associated with lower odds of receiving government assistance. CONCLUSIONS: After a pediatric cancer diagnosis, low-to-middle-income families are more likely to incur debt than high-income families. Most families experiencing food insecurity received some food assistance, while housing and energy assistance were less common. Future studies should investigate methods to equitably improve access to financial assistance and minimize long-term financial consequences.


Assuntos
Capacidades de Enfrentamento , Neoplasias , Criança , Humanos , Estudos Retrospectivos , Pobreza , Renda , Neoplasias/diagnóstico
7.
New Phytol ; 242(6): 2719-2733, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38229566

RESUMO

The chemical arms race between plants and insects is foundational to the generation and maintenance of biological diversity. We asked how the evolution of a novel defensive compound in an already well-defended plant lineage impacts interactions with diverse herbivores. Erysimum cheiranthoides (Brassicaceae), which produces both ancestral glucosinolates and novel cardiac glycosides, served as a model. We analyzed gene expression to identify cardiac glycoside biosynthetic enzymes in E. cheiranthoides and characterized these enzymes via heterologous expression and CRISPR/Cas9 knockout. Using E. cheiranthoides cardiac glycoside-deficient lines, we conducted insect experiments in both the laboratory and field. EcCYP87A126 initiates cardiac glycoside biosynthesis via sterol side-chain cleavage, and EcCYP716A418 has a role in cardiac glycoside hydroxylation. In EcCYP87A126 knockout lines, cardiac glycoside production was eliminated. Laboratory experiments with these lines revealed that cardiac glycosides were highly effective defenses against two species of glucosinolate-tolerant specialist herbivores, but did not protect against all crucifer-feeding specialist herbivores in the field. Cardiac glycosides had lesser to no effect on two broad generalist herbivores. These results begin elucidation of the E. cheiranthoides cardiac glycoside biosynthetic pathway and demonstrate in vivo that cardiac glycoside production allows Erysimum to escape from some, but not all, specialist herbivores.


Assuntos
Glicosídeos Cardíacos , Erysimum , Glucosinolatos , Herbivoria , Glucosinolatos/metabolismo , Animais , Glicosídeos Cardíacos/farmacologia , Erysimum/metabolismo , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Adaptação Fisiológica/genética , Adaptação Fisiológica/efeitos dos fármacos
8.
Ecol Lett ; 27(1): e14340, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38017619

RESUMO

Herbivores that sequester toxins are thought to have cracked the code of plant defences. Nonetheless, coevolutionary theory predicts that plants should evolve toxic variants that also negatively impact specialists. We propose and test the selective sequestration hypothesis, that specialists preferentially sequester compounds that are less toxic to themselves while maintaining toxicity to enemies. Using chemically distinct plants, we show that monarch butterflies sequester only a subset of cardenolides from milkweed leaves that are less potent against their target enzyme (Na+ /K+ -ATPase) compared to several dominant cardenolides from leaves. However, sequestered compounds remain highly potent against sensitive Na+ /K+ -ATPases found in most predators. We confirmed this differential toxicity with mixtures of purified cardenolides from leaves and butterflies. The genetic basis of monarch adaptation to sequestered cardenolides was also confirmed with transgenic Drosophila that were CRISPR-edited with the monarch's Na+ /K+ -ATPase. Thus, the monarch's selective sequestration appears to reduce self-harm while maintaining protection from enemies.


Assuntos
Asclepias , Borboletas , Animais , Borboletas/genética , Larva , Asclepias/química , Cardenolídeos/toxicidade , Adenosina Trifosfatases
9.
J Chem Ecol ; 50(1-2): 52-62, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37932621

RESUMO

Plants have evolved a diverse arsenal of defensive secondary metabolites in their evolutionary arms race with insect herbivores. In addition to the bottom-up forces created by plant chemicals, herbivores face top-down pressure from natural enemies, such as predators, parasitoids and parasites. This has led to the evolution of specialist herbivores that do not only tolerate plant secondary metabolites but even use them to fight natural enemies. Monarch butterflies (Danaus plexippus) are known for their use of milkweed chemicals (cardenolides) as protection against vertebrate predators. Recent studies have shown that milkweeds with high cardenolide concentrations can also provide protection against a virulent protozoan parasite. However, whether cardenolides are directly responsible for these effects, and whether individual cardenolides or mixtures of these chemicals are needed to reduce infection, remains unknown. We fed monarch larvae the four most abundant cardenolides found in the anti-parasitic-milkweed Asclepias curassavica at varying concentrations and compositions to determine which provided the highest resistance to parasite infection. Measuring infection rates and infection intensities, we found that resistance is dependent on both concentration and composition of cardenolides, with mixtures of cardenolides performing significantly better than individual compounds, even when mixtures included lower concentrations of individual compounds. These results suggest that cardenolides function synergistically to provide resistance against parasite infection and help explain why only milkweed species that produce diverse cardenolide compounds provide measurable parasite resistance. More broadly, our results suggest that herbivores can benefit from consuming plants with diverse defensive chemical compounds through release from parasitism.


Assuntos
Asclepias , Borboletas , Parasitos , Doenças Parasitárias , Animais , Borboletas/metabolismo , Asclepias/química , Cardenolídeos/farmacologia , Cardenolídeos/metabolismo , Larva/metabolismo
10.
Eur J Med Res ; 28(1): 556, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049897

RESUMO

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.


Assuntos
COVID-19 , Justicia , Tinospora , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , Biomarcadores , Ferritinas , Hipóxia , Resultado do Tratamento
11.
Sci Rep ; 13(1): 20437, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993590

RESUMO

Urbanization is altering landscapes globally at an unprecedented rate. While ecological differences between urban and rural environments often promote phenotypic divergence among populations, it is unclear to what degree these trait differences arise from genetic divergence as opposed to phenotypic plasticity. Furthermore, little is known about how specific landscape elements, such as green corridors, impact genetic divergence in urban environments. We tested the hypotheses that: (1) urbanization, and (2) proximity to an urban green corridor influence genetic divergence in common milkweed (Asclepias syriaca) populations for phenotypic traits. Using seeds from 52 populations along three urban-to-rural subtransects in the Greater Toronto Area, Canada, one of which followed a green corridor, we grew ~ 1000 plants in a common garden setup and measured > 20 ecologically-important traits associated with plant defense/damage, reproduction, and growth over four years. We found significant heritable variation for nine traits within common milkweed populations and weak phenotypic divergence among populations. However, neither urbanization nor an urban green corridor influenced genetic divergence in individual traits or multivariate phenotype. These findings contrast with the expanding literature demonstrating that urbanization promotes rapid evolutionary change and offer preliminary insights into the eco-evolutionary role of green corridors in urban environments.


Assuntos
Asclepias , Urbanização , Asclepias/genética , Deriva Genética , Evolução Biológica , Adaptação Fisiológica
12.
Cell Mol Life Sci ; 80(12): 357, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950757

RESUMO

Idiopathic Pulmonary Fibrosis (IPF) is a progressively fatal and incurable disease characterized by the loss of alveolar structures, increased epithelial-mesenchymal transition (EMT), and aberrant tissue repair. In this study, we investigated the role of Nuclear Factor I-B (NFIB), a transcription factor critical for lung development and maturation, in IPF. Using both human lung tissue samples from patients with IPF, and a mouse model of lung fibrosis induced by bleomycin, we showed that there was a significant reduction of NFIB both in the lungs of patients and mice with IPF. Furthermore, our in vitro experiments using cultured human lung cells demonstrated that the loss of NFIB was associated with the induction of EMT by transforming growth factor beta (TGF-ß). Knockdown of NFIB promoted EMT, while overexpression of NFIB suppressed EMT and attenuated the severity of bleomycin-induced lung fibrosis in mice. Mechanistically, we identified post-translational regulation of NFIB by miR-326, a miRNA with anti-fibrotic effects that is diminished in IPF. Specifically, we showed that miR-326 stabilized and increased the expression of NFIB through its 3'UTR target sites for Human antigen R (HuR). Moreover, treatment of mice with either NFIB plasmid or miR-326 reversed airway collagen deposition and fibrosis. In conclusion, our study emphasizes the critical role of NFIB in lung development and maturation, and its reduction in IPF leading to EMT and loss of alveolar structures. Our study highlights the potential of miR-326 as a therapeutic intervention for IPF. The schema shows the role of NFIB in maintaining the normal epithelial cell characteristics in the lungs and how its reduction leads to a shift towards mesenchymal cell-like features and pulmonary fibrosis. A In normal lungs, NFIB is expressed abundantly in the epithelial cells, which helps in maintaining their shape, cell polarity and adhesion molecules. However, when the lungs are exposed to factors that induce pulmonary fibrosis, such as bleomycin, or TGF-ß, the epithelial cells undergo epithelial to mesenchymal transition (EMT), which leads to a decrease in NFIB. B The mesenchymal cells that arise from EMT appear as spindle-shaped with loss of cell junctions, increased cell migration, loss of polarity and expression of markers associated with mesenchymal cells/fibroblasts. C We designed a therapeutic approach that involves exogenous administration of NFIB in the form of overexpression plasmid or microRNA-326. This therapeutic approach decreases the mesenchymal cell phenotype and restores the epithelial cell phenotype, thus preventing the development or progression of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , MicroRNAs , Humanos , Camundongos , Animais , Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fatores de Transcrição NFI/metabolismo , Fatores de Transcrição NFI/farmacologia , Pulmão/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , MicroRNAs/metabolismo , Células Epiteliais/metabolismo , Bleomicina/toxicidade
13.
bioRxiv ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37790475

RESUMO

The chemical arms race between plants and insects is foundational to the generation and maintenance of biological diversity. We asked how the evolution of a novel defensive compound in an already well-defended plant lineage impacts interactions with diverse herbivores. Erysimum cheiranthoides (Brassicaceae), which produces both ancestral glucosinolates and novel cardiac glycosides, served as a model.We analyzed gene expression to identify cardiac glycoside biosynthetic enzymes in E. cheiranthoides and characterized these enzymes via heterologous expression and CRISPR/Cas9 knockout. Using E. cheiranthoides cardiac glycoside-deficient lines, we conducted insect experiments in both the laboratory and field.EcCYP87A126 initiates cardiac glycoside biosynthesis via sterol side chain cleavage, and EcCYP716A418 has a role in cardiac glycoside hydroxylation. In EcCYP87A126 knockout lines, cardiac glycoside production was eliminated. Laboratory experiments with these lines revealed that cardiac glycosides were highly effective defenses against two species of glucosinolate-tolerant specialist herbivores but did not protect against all crucifer-feeding specialist herbivores in the field. Cardiac glycosides had lesser to no effect on two broad generalist herbivores.These results begin elucidation of the E. cheiranthoides cardiac glycoside biosynthetic pathway and demonstrate in vivo that cardiac glycoside production allows Erysimum to escape from some, but not all, specialist herbivores.

15.
Evolution ; 77(11): 2431-2441, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37656826

RESUMO

A major predicted constraint on the evolution of anti-herbivore defense in plants is the nonindependent expression of traits mediating resistance. Since herbivore attack can be highly variable across plant tissues, we hypothesized that correlations in toxin expression within and between plant tissues may limit population differentiation and, thus, plant adaptation. Using full-sib families from two nearby (<1 km) common milkweed (Asclepias syriaca) populations, we investigated genetic correlations among 28 distinct cardenolide toxins within and between roots, leaves, and seeds and examined signatures of tissue-specific divergent selection between populations by QST-FST comparisons. The prevalence, direction, and strength of genetic correlations among cardenolides were tissue specific, and concentrations of individual cardenolides were moderately correlated between tissues; nonetheless, the direction and strength of correlations were population specific. Population divergence in the cardenolide chemistry was stronger in roots than in leaves and seeds. Divergent selection on individual cardenolides was tissue and toxin specific, except for a single highly toxic cardenolide (labriformin), that showed divergent selection across all plant tissues. Heterogeneous evolution of cardenolides within and between tissues across populations appears possible due to their highly independent expression. This independence may be common in nature, especially in specialized interactions in which distinct herbivores feed on different plant tissues.


Assuntos
Asclepias , Borboletas , Humanos , Animais , Borboletas/metabolismo , Herbivoria , Plantas , Cardenolídeos/metabolismo , Cardenolídeos/toxicidade , Asclepias/metabolismo
16.
Lancet Microbe ; 4(10): e830-e836, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37640039

RESUMO

A systematic approach is required for the development of an evidence-based risk assessment tool to robustly estimate the risks and implications of SARS-CoV-2 variants. We conducted a survey among experts involved in technical advisory roles for WHO to capture their assessment of the robustness of different study types that provide evidence for potential changes in transmissibility, antigenicity, virulence, treatability, and detectability of SARS-CoV-2 variants. The views of 62 experts indicated that studies could be grouped on the basis of robustness and reliability for the different risk indicators mentioned. Several study types that experts scored as providing reliable evidence and that can be performed in a timely manner were identified. Although experts from different technical areas had varying responses, there was agreement on the highest and lowest scoring study types. These findings can help to prioritise, harmonise, and optimise study designs for the further development of a systematic, evidence-based, SARS-CoV-2 variant risk assessment tool.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Reprodutibilidade dos Testes , SARS-CoV-2/genética , Medição de Risco , Encaminhamento e Consulta
17.
Curr Biol ; 33(17): 3702-3710.e5, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37607548

RESUMO

In intimate ecological interactions, the interdependency of species may result in correlated demographic histories. For species of conservation concern, understanding the long-term dynamics of such interactions may shed light on the drivers of population decline. Here, we address the demographic history of the monarch butterfly, Danaus plexippus, and its dominant host plant, the common milkweed Asclepias syriaca (A. syriaca), using broad-scale sampling and genomic inference. Because genetic resources for milkweed have lagged behind those for monarchs, we first release a chromosome-level genome assembly and annotation for common milkweed. Next, we show that despite its enormous geographic range across eastern North America, A. syriaca is best characterized as a single, roughly panmictic population. Using approximate Bayesian computation with random forests (ABC-RF), a machine learning method for reconstructing demographic histories, we show that both monarchs and milkweed experienced population expansion during the most recent recession of North American glaciers 10,000-20,000 years ago. Our data also identify concurrent population expansions in both species during the large-scale clearing of eastern forests (∼200 years ago). Finally, we find no evidence that either species experienced a reduction in effective population size over the past 75 years. Thus, the well-documented decline of monarch abundance over the past 40 years is not visible in our genomic dataset, reflecting a possible mismatch of the overwintering census population to effective population size in this species.


Assuntos
Asclepias , Borboletas , Animais , Asclepias/genética , Borboletas/genética , Teorema de Bayes , Densidade Demográfica , Genômica
18.
Proc Biol Sci ; 290(2004): 20230987, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37554038

RESUMO

Plant toxicity shapes the dietary choices of herbivores. Especially when herbivores sequester plant toxins, they may experience a trade-off between gaining protection from natural enemies and avoiding toxicity. The availability of toxins for sequestration may additionally trade off with the nutritional quality of a potential food source for sequestering herbivores. We hypothesized that diet mixing might allow a sequestering herbivore to balance nutrition and defence (via sequestration of plant toxins). Accordingly, here we address diet mixing and sequestration of large milkweed bugs (Oncopeltus fasciatus) when they have differential access to toxins (cardenolides) in their diet. In the absence of toxins from a preferred food (milkweed seeds), large milkweed bugs fed on nutritionally adequate non-toxic seeds, but supplemented their diet by feeding on nutritionally poor, but cardenolide-rich milkweed leaf and stem tissues. This dietary shift corresponded to reduced insect growth but facilitated sequestration of defensive toxins. Plant production of cardenolides was also substantially induced by bug feeding on leaf and stem tissues, perhaps benefitting this cardenolide-resistant herbivore. Thus, sequestration appears to drive diet mixing in this toxic plant generalist, even at the cost of feeding on nutritionally poor plant tissue.


Assuntos
Asclepias , Plantas Tóxicas , Herbivoria , Dieta , Cardenolídeos
19.
Sci Rep ; 13(1): 11038, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37419941

RESUMO

The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.


Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Hiperglicemia , Humanos , Disbiose/microbiologia , Duodeno/microbiologia , Bactérias
20.
Artigo em Inglês | MEDLINE | ID: mdl-37464823

RESUMO

BACKGROUND: Several studies have been conducted on 4-H chromene compounds because of their intriguing pharmacological and biological properties. Various new natural compounds having a chromene foundation have been reported over the past 20 years. OBJECTIVE: In the present study, we reported the acute oral toxicity, antioxidant activity, and molecular docking study of the most active 4H-chromene derivative2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4-chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide (A9). METHOD: The acute oral toxicity was carried out as per OECD 423 guidelines. For investigating the antioxidant activity, various biochemical parameters in colon tissue like SOD, CAT, MDA, PC and GSH and also enzyme levels, such as ALT, AST, ALP, and LDH, were measured in this experiment. RESULTS: Acute oral toxicity study indicated that the A9 ligand was found to be safer in animals. Additionally, the A9 ligand had significant antioxidant properties at various doses and was not found to be harmful to the liver. Due to its stronger binding energy and the appropriate interactions that induce inhibition, the A9 ligand's antioxidant function was also validated by additional molecular docking research. CONCLUSION: This compound can be exploited as a lead molecule in further research.

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