Plants of the genus
have been frequently reported as important medicinal plants. Despite their high bioactive potential, to date, there are no reports of their effects on leaf-cutting ants. ...Therefore, the present study aimed to evaluate the insecticidal activity of the essential oil of
and its major components on
and
, two species of leaf-cutting ants. The bioassays were performed regarding routes of exposure, acute toxicity, binary mixtures of the major components and behavioral effects. Twenty-five components were identified in the essential oil of
using a gas chromatographic system equipped with a mass spectrometer and a flame ionization detector. The components found in higher proportions were sulcatyl acetate, limonene,
-cymene and linalool. The essential oil of
and its individual major components were efficient against
and
workers when applied by fumigation. These components showed fast and efficient insecticidal activity on ants. The components acted synergistically and additively on
and
, respectively, and caused a strong repellency/irritability in the ants. Thus, our results demonstrate the great potential of the essential oil of
and its major components for the development of new insecticides.
Abstract
The ability to identify B-cell epitopes is an essential step in vaccine design, immunodiagnostic tests and antibody production. Several computational approaches have been proposed to ...identify, from an antigen protein or peptide sequence, which residues are more likely to be part of an epitope, but have limited performance on relatively homogeneous data sets and lack interpretability, limiting biological insights that could otherwise be obtained. To address these limitations, we have developed epitope1D, an explainable machine learning method capable of accurately identifying linear B-cell epitopes, leveraging two new descriptors: a graph-based signature representation of protein sequences, based on our well-established Cutoff Scanning Matrix algorithm and Organism Ontology information. Our model achieved Areas Under the ROC curve of up to 0.935 on cross-validation and blind tests, demonstrating robust performance. A comprehensive comparison to alternative methods using distinct benchmark data sets was also employed, with our model outperforming state-of-the-art tools. epitope1D represents not only a significant advance in predictive performance, but also allows biologically meaningful features to be combined and used for model interpretation. epitope1D has been made available as a user-friendly web server interface and application programming interface at https://biosig.lab.uq.edu.au/epitope1d/.
The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic control, which integrates thermoregulation centers and sympathetic outflow to thermoeffector organs. PVN ...neurons express the neuronal isoform of nitric oxide synthase (nNOS) whose expression is locally upregulated by physical exercise. Thus, the aim of the present study was to evaluate the role of nNOS in the PVN in the exercise-induced hyperthermia. Seven days after surgery, male Wistar rats received bilateral intra-PVN microinjections of the selective nNOS inhibitor Nw-Propyl-L-Arginine (NPLA) or vehicle (saline) and were submitted to an acute progressive exercise session on a treadmill until fatigue. Abdominal and tail skin temperature (Tabd and Ttail, respectively) were measured, and the threshold (Hthr; °C) and sensitivity (Hsen) for heat dissipation calculated. Performance variables were also collected. During the progressive exercise protocol, all animals displayed an increase in the Tabd. However, compared to vehicle group, the microinjection of NPLA in the PVN attenuated the exercise-induced hyperthermia. There was no difference in Ttail or Hthr between NPLA and control rats. In contrast, Hsen was increased in the NPLA group compared to vehicle. In addition, heat storage was lower in NPLA-treated animals. Despite the temperature differences, inhibition of nNOS in the PVN did not affect running performance on the treadmill. These results suggest that nitrergic signaling within the PVN, under nNOS activation, drives the increase of body temperature, being necessary for the proper thermal regulatory mechanisms during progressive exercise-induced hyperthermia.
•The effect of PVN nNOS inhibition in the exercise-induced hyperthermia was assessed.•PVN nNOS inhibition decreased hyperthermia in response to a progressive exercise.•The sensitivity for heat dissipation was increased with PVN nNOS inhibition.•No difference was found in the skin tail temperature during exercise.•PVN nitrergic signaling is required for proper thermal responses during exercise.
Breast cancer is associated with a high mortality rate around the world due to its aggressiveness and high resistance to conventional therapies. Sanguinarine (SAN) and Chelerythrine (CHE) are plant ...alkaloids extracted from Sanguinaria canadensis and Macleaya cordata, which have been studied for their bioactivities.
To determine the anticancer activities of Sanguinarine (SAN) and Chelerythrine (CHE) plant alkaloids.
The MTT assay, the alkaline comet assay and cell cycle analyses by flow cytometry were performed.
It was observed that SAN was cytotoxic to human breast adenocarcinoma cells (MCF-7) at concentrations of 7.5 µM (24 and 48 hours), effectively reducing cell viability from the concentration of 10 µM for 24 hours and 7.5 µM for 48 hours, by the MTT test. CHE, in turn, was cytotoxic at concentrations of 10 and 20 µM (48 hours), but did not compromise the cellular viability. The comet assay indicated that SAN was genotoxic to the MCF-7 cells, with a significant increment of damage at 10 µM, while none of the tested concentrations of CHE showed a genotoxic effect. The flow cytometry analysis indicated that no cell cycle arrest was caused by both alkaloids, but SAN 10 µM induced a sub-G1 cell population.
The results of cytotoxicity, genotoxicity and cell cycle monitoring that are presented in this paper have suggested that SAN has more of a chemotherapeutic activity, as well as having the potential for the development of new therapies for breast cancer, when compared to CHE.
Abstract
The ability to identify antigenic determinants of pathogens, or epitopes, is fundamental to guide rational vaccine development and immunotherapies, which are particularly relevant for rapid ...pandemic response. A range of computational tools has been developed over the past two decades to assist in epitope prediction; however, they have presented limited performance and generalization, particularly for the identification of conformational B-cell epitopes. Here, we present epitope3D, a novel scalable machine learning method capable of accurately identifying conformational epitopes trained and evaluated on the largest curated epitope data set to date. Our method uses the concept of graph-based signatures to model epitope and non-epitope regions as graphs and extract distance patterns that are used as evidence to train and test predictive models. We show epitope3D outperforms available alternative approaches, achieving Mathew’s Correlation Coefficient and F1-scores of 0.55 and 0.57 on cross-validation and 0.45 and 0.36 during independent blind tests, respectively.
Over 66 million people worldwide have been diagnosed with COVID-19. Therefore, understanding their clinical evolution beyond hospital discharge is essential not only from an individual standpoint, ...but from a populational level.
Our primary aim was to assess the impact of COVID-19 on health-related quality of life (HRQoL) 3 months after hospital discharge. Additionally, we screened for anxiety and depression and assessed important clinical outcomes.
This was a single-center cohort study performed in Sao Paulo (Brazil), in which participants were contacted by telephone to answer a short survey. EQ-5D-3L was used to assess HRQoL and clinical data from patients’ index admission were retrieved from medical records.
We contacted 251 participants (59.8% males, mean age 53 years old), 69.7% of which had presented with severe COVID-19. At 3 months of follow-up, 6 patients had died, 51 (20.3%) had visited the emergency department again and 17 (6.8%) had been readmitted to hospital. Seventy patients (27.9%) persisted with increased dyspnoea and 81 had a positive screening for anxiety/depression. Similarly, patients reported an overall worsening of EQ-5D-3L single summary index at 3 months compared to before the onset of COVID-19 symptoms (0.8012 (0.7368 – 1.0) vs. 1.0(0.7368 – 1.0), p < 0.001). This affected all 5 domains, but especially pain/discomfort and anxiety/depression. Only female sex and intensive care requirement were independently associated with worsening of HRQoL.
Patients hospitalized for COVID-19 frequently face persistent clinical and mental health problems up to 3 months following hospital discharge, with significant impact on patients’ HRQoL.
•COVID-19 admission is associated with persistent clinical and mental health problems.•Dyspnoea persists up to 3 months following hospital discharge in many patients.•HRQoL is significantly worsened up to 3 months following hospital discharge.•Pain/discomfort and anxiety/depression were the most impacted domains of HRQoL.•Female sex and intensive care requirement were associated with worsening of HRQoL.
Differentiation status of tumors is correlated with metastatic potential and malignancy. FOXA1 (forkhead box A1) is a transcription factor known to regulate differentiation in certain tissues. Here, ...we investigate FOXA1 function in human colorectal cancer (CRC). We found that FOXA1 is robustly expressed in the normal human colon but significantly downregulated in colon adenocarcinoma. Applying FOXA1 chromatin immunoprecipitation coupled with deep sequencing and transcriptome analysis upon FOXA1 knockdown in well-differentiated CRC cells and FOXA1 overexpression in poorly differentiated CRC cells, we identified novel protein-coding and lncRNA genes regulated by FOXA1. Among the numerous novel FOXA1 targets we identified, we focused on CEACAM5, a tumor marker and facilitator of cell adhesion. We show that FOXA1 binds to a distal enhancer downstream of CEACAM5 and strongly activates its expression. Consistent with these data, we show that FOXA1 inhibits anoikis in CRC cells. Collectively, our results uncover novel protein-coding and noncoding targets of FOXA1 and suggest a vital role of FOXA1 in enhancing CEACAM5 expression and anoikis resistance in CRC cells.
Sugarcane (
spp.) is an important crop for sugar and bioethanol production worldwide. To maintain and increase sugarcane yields in marginal areas, the use of nitrogen (N) fertilizers is essential, ...but N overuse may result in the leaching of reactive N to the natural environment. Despite the importance of N in sugarcane production, little is known about the molecular mechanisms involved in N homeostasis in this crop, particularly regarding ammonium (NH
), the sugarcane's preferred source of N. Here, using a sugarcane bacterial artificial chromosome (BAC) library and a series of
analyses, we identified an
(
) from the AMT2 subfamily, sugarcane
(
), which is constitutively and highly expressed in young and mature leaves. To characterize its biochemical function, we ectopically expressed
in heterologous systems (
and
). The complementation of triple
mutant yeast demonstrated that ScAMT3;3 is functional for NH
/H
cotransport at high availability of NH
and under physiological pH conditions. The ectopic expression of
in the
quadruple
knockout mutant restored the transport capacity of
N-NH
in roots and plant growth under specific N availability conditions, confirming the role of ScAMT3;3 in NH
transport
. Our results indicate that ScAMT3;3 belongs to the low-affinity transport system (
270.9 µM;
209.3 µmol g
root DW h
). We were able to infer that ScAMT3;3 plays a presumed role in NH
source-sink remobilization in the shoots via phloem loading. These findings help to shed light on the functionality of a novel AMT2-type protein and provide bases for future research focusing on the improvement of sugarcane yield and N use efficiency.
Several chemical changes occur during the ripening of dry-fermented sausages that determine the flavor and odor of the end product. The phenomena that take place during fermentation, that is, both ...acidification of the sugars by lactic acid bacteria and reduction of nitrates and nitrites to nitric oxide by micrococci have been known for several years. However, the chemical changes involved in this process, and, particularly, the agents responsible have not yet been established, although they have been attributed to changes in the majority components (proteins and lipids) and to the ingredients added (spices and condiments) in the preparation of the original mixture. The typical flavor and odor of dry-fermented sausages cannot be attributed to volatile substances alone, but to a large number of volatile and nonvolatile compounds present in the product in suitable proportions. Microbial growth in the sausage together with activity of the meat endogenous enzymes are undoubtedly partially responsible for the development of a number of aromatic and sapid compounds. However, lipid autooxidation reactions are also an important source of these substances, and it is not yet known which of these processes is more important in sausage ripening. Much research has focused on the break up of triglycerides into free fatty acids, diglycerides, and monoglycerides during ripening and the progressive increase in the amounts of different carbonyl oxidation products. Carbonyl compounds probably play a significant role in determining the flavor because, in general, these have very low perception thresholds, in the ppm and ppb range. Similarly, the protein breakdown to yield peptides and amino acids has been studied extensively, the latter being substrates of several microbial and chemical reactions that generate many flavor compounds.
Cutaneous squamous cell carcinoma (cSCC) and melanoma have different associations with sun exposure.
To compare trends in the incidence rates of cSCC and melanoma, to provide insight into changing ...patterns of exposure to ultraviolet radiation (UVR).
We compared trends in the incidence of cSCC and melanoma in seven susceptible populations residing at mid-to-high latitudes: Finland, Norway, Sweden, Denmark, Scotland, the Netherlands and Tasmania (Australia). We fitted Joinpoint models to describe trends in age-standardized incidence rates for melanoma and cSCC and calculated the average annual percentage rate of change for the period 1989-2020 (1989-2018 for Tasmania). We calculated the incident rate ratio (IRR) as the ratio of the age-standardized rates (European Standard Population) for cSCC to melanoma and conducted age-period-cohort modelling to compare age, period and cohort effects.
The ratio of cSCC-to-melanoma incidence increased with proximity to the equator and over time. In the most recent time period, the incidence of cSCC was higher than the incidence of melanoma for men and women in all seven populations. While the ratio of cSCC-to-melanoma incidence was higher for men vs. women, in most countries the cSCC-to-melanoma IRR increased over time to a greater extent in women than in men. Melanoma incidence was higher among younger people and cSCC incidence was higher among older people; the age at which the incidence of cSCC overtook the incidence of melanoma was progressively younger with proximity to the equator.
Despite concerted international efforts to preserve the ozone layer over the past four decades resulting in significant reductions in surface ultraviolet B at mid-latitudes, the incidence of skin cancer, particularly cSCC, continues to rise in those regions. Our findings are consistent with a stronger association with age-associated cumulative sun exposure for cSCC vs. melanoma and suggest that women are currently receiving greater UV radiation exposure than in the past.
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