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Corticotropin releasing factor (CRF) is the key coordinator of the neuroendocrine and behavioral responses to stress. In the central nervous system, CRF excites select neuronal populations, and infusion of CRF into the cerebral ventricles of infant rats produces severe age-dependent limbic seizures. These seizures, like other CRF effects, result from activation of specific receptors. Both of the characterized members of the CRF receptor family (CRF1 and CRF2), are found in the amygdala, site of origin of CRF-induced seizures, and may therefore mediate these seizures. To determine which receptor is responsible for the excitatory effects of CRF on limbic neurons, a selective, non-peptide CRF1 antagonist was tested for its ability to abolish the seizures, in comparison to non-selective inhibitory analogues of CRF. Pretreatment with the selective CRF1 blocker (NBI 27914) increased the latency and decreased the duration of CRF-induced seizures in a dose-dependent manner. The higher doses of NBI 27914 blocked the behavioral seizures and prevented epileptic discharges in concurrent electroencephalograms recorded from the amygdala. The selective CRF1 blocker was poorly effective when given systemically, consistent with limited blood-brain barrier penetration. Urocortin, a novel peptide activating both types of CRF receptors in vitro, but with preferential affinity for CRF2 receptors in vivo, produced seizures with a lower potency than CRF. These limbic seizures, indistinguishable from those induced by CRF, were abolished by pretreatment with NBI 27914, consistent with their dependence on CRF1 activation. In summary, CRF induces limbic seizures in the immature rat, which are abolished by selective blocking of the CRF1 receptor. CRF1-messenger RNA levels are maximal in sites of seizure origin and propagation during the age when CRF is most potent as a convulsant. Taken together, these facts strongly support the role of the developmentally regulated CRF1 receptor in mediating the convulsant effects of CRF in the developing brain.

In Alzheimer's disease (AD) there are dramatic reductions in the content of corticotropin releasing factor (CRF), reciprocal increases in CRF receptors, and morphological abnormalities in CRF neurons in affected brain areas. Cognitive impairment in AD patients is associated with a lower cerebrospinal fluid concentration of CRF, which is known to induce increases in learning and memory in rodents. This suggests that CRF deficits contribute to cognitive impairment. The identification in post-mortem brain of CRF-binding protein (CRF-BP), a high-affinity binding protein that inactivates CRF, and the differential distribution of CRF-BP and CRF receptors, provides the potential for improving learning and memory without stress effects of CRF receptor agonists. Here we show that ligands that dissociate CRF from CRF-BP increase brain levels of 'free CRF' in AD to control levels and show cognition-enhancing properties in models of learning and memory in animals without the characteristic stress effects of CRF receptor agonists.

Melastomataceae comprises to 5,858 plant species across 173 genera globally. Brazil hosts the highest diversity for this family, including 1,453 species, with a great number of endemics. The Brazilian Caatinga is an important domain for Seasonally Dry Tropical Forests, Shrubs and Woodlands in South America, highlighting exceptional environmental diversity and hosting endemic and rare species. While the representation of Melastomataceae in the Caatinga is limited, the colonization of xeric environments by select species has garnered attention. One of these is Pleroma caatingae, a threatened species previously thought to be endemic to the state of Bahia, and recently collected in the Ceará state. This study provides an updated morphological description and uses a predictive Species Distribution Model (SDM) to predict potential species' distribution and conservation status. The findings not only enhance knowledge of neotropical species distribution patterns, but also highlight the importance of preserving overlooked arid habitats, such as the inselbergs, which harbor intriguing biodiversity as well.

Climate change is among the principal threats to global terrestrial biodiversity, especially to megadiverse ecosystems such as the Amazon rainforest. In this study, we investigate how it could affect an iconic forest species-Bertholletia excelsa-(the Brazil nut) which has values in multiple dimensions in an Amazonian context. We used an ensemble from various distribution modeling methods designed for four different climate scenarios from CMIP6 by the end of the century. Then, we simulate how spatial dynamics under climate change, including explicitly dispersal events, can affect the persistence, colonization, and potential extinction of Bertholletia excelsa in the future. Our results show that by the end of the century there would be a generalized loss of suitability on the Amazon biome, regardless of the climate scenario evaluated, which could promote a significant loss (up to 94%) of the area available for the species via extinction. Our results also show that, in the future, the species would colonize higher altitudes in search of favorable conditions for its survival. Finally, we detected that areas that had previously become unsuitable because of climate change would have favorable conditions by the end of the century. Such an outcome could be useful in fostering an active restoration agenda that can mitigate the negative effects of climate change on species in this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Anjos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Moko disease in banana is a bacterial wilt caused by strains within Ralstonia solanacearum sensu stricto. The disease is endemic to Central and South America but has spread to the Philippines and peninsular Malaysia. Detecting new incursions early in Moko-free banana production regions is of utmost importance for containment and eradication, as Moko management significantly increases costs in banana production. Molecular studies have supported the classification of R. solanacearum sensu stricto into phylotypes IIA, IIB, and IIC, each comprising various sequevars based on nucleotide divergence of a partial sequence within the endoglucanase gene. Moko disease in banana is caused by strains classified as sequevars 6, 24, 41, and 53 within phylotype IIA and sequevars 3, 4, and 25 within phylotype IIB. To ensure accurate diagnostic assays are available to detect all Moko sequevars, we systematically validated previously published assays for Moko diagnostics. To be able to identify all sequevars, including the latest described sequevars, namely IIB-25, IIA-41, and IIA-53, we developed and validated two novel assays using genome-wide association studies on over 100 genomes of R. solanacearum sensu stricto. Validations using 196 bacterial isolates confirmed that a previous multiplex PCR-based assay targeting sequevars IIB-3, IIB-4, IIA-6, and IIA-24 and our two novel assays targeting sequevars IIB-25, IIA-41, and IIA-53 were specific, reproducible, and accurate for Moko diagnostics., Competing Interests: The author(s) declare no conflict of interest.

In reproductive technologies, uncovering the molecular aspects of oocyte and embryo competence under different conditions is crucial for refining protocols and enhancing efficiency. RNA-seq generates high-throughput data and provides transcriptomes that can undergo additional computational analyses. This study presented the transcriptomic profiles of in vitro matured oocytes and blastocysts produced in vitro from buffalo crossbred ( Bubalus bubalis ), coupled with gene co-expression and module preservation analysis. Cumulus Oophorus Complexes, obtained from slaughterhouse-derived ovaries, were subjected to in vitro maturation to yield metaphase II oocytes (616) or followed in vitro fertilization and culture to yield blastocysts for sequencing (526). Oocyte maturation (72%, ±3.34 sd) and embryo development (21.3%, ±4.18 sd) rates were obtained from three in vitro embryo production routines following standard protocols. Sequencing of 410 metaphase II oocytes and 70 hatched blastocysts (grade 1 and 2) identified a total of 13,976 genes, with 62% being ubiquitously expressed (8,649). Among them, the differentially expressed genes (4,153) and the strongly variable genes with the higher expression (fold-change above 11) were highlighted in oocytes ( BMP15 , UCHL1 , WEE1 , NLRPs, KPNA7 , ZP2, and ZP4 ) and blastocysts ( APOA1 , KRT18 , ANXA2 , S100A14 , SLC34A2 , PRSS8 and ANXA2 ) as representative indicators of molecular quality. Additionally, genes exclusively found in oocytes (224) and blastocysts (2,200) with specific biological functions were identified. Gene co-expression network and module preservation analysis revealed strong preservation of functional modules related to exosome components, steroid metabolism, cell proliferation, and morphogenesis. However, cell cycle and amino acid transport modules exhibited weak preservation, which may reflect differences in embryo development kinetics and the activation of cell signaling pathways between buffalo and bovine. This comprehensive transcriptomic profile serves as a valuable resource for assessing the molecular quality of buffalo oocytes and embryos in future in vitro embryo production assays., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)

One of the crucial aspects to be considered for successful in vitro production (IVP) of embryos is the composition of the various media used throughout the stages of this reproductive biotechnology. The cell culture media employed should fulfill the metabolic requirements of both gametes during oocyte maturation and sperm development, as well as the embryo during its initial cell divisions. Most IVP protocols incorporate blood serum into the media composition as a source of hormones, proteins, growth factors, and nutrients. Numerous studies have suggested Platelet-Rich Plasma (PRP) as a substitute for fetal sera in cell culture, particularly for stem cells. Therefore, the objective of this study is to assess the potential use of PRP as a replacement for fetal bovine serum (FBS) during oocyte maturation for in vitro production of bovine embryos. During in vitro maturation (IVM), cumulus-oocyte complexes (COCs) were allocated into the following experimental groups: Group G1 (IVM medium with 5% PRP); Group G2 (MIV medium with 5% PRP and 5% SFB); Group G3 (MIV medium with 5% SFB); and Group G4 (MIV medium without either PRP or SFB). Subsequently, the cumulus-oocyte complexes were fertilized with semen from a single bull, and the resulting zygotes were cultured for seven days. Cleavage and blastocyst formation rates were assessed on days 2 and 7 of embryonic development, respectively. The quality of matured COCs was also evaluated by analyzing the gene expression of HSP70, an important protein associated with cellular stress. The results demonstrated that there were no significant differences among the experimental groups in terms of embryo production rates, both in the initial cleavage stages and blastocyst formation (except for the G4 group, which exhibited a lower blastocyst formation rate on D7, as expected). This indicates that PRP could be a cost-effective alternative to SFB in the IVP of embryos., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

This work describes the characterization of BNC210 (6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(4-morpholinylcarbonyl)-1,8-naphthyridin-4(1H)-one), a selective, small molecule, negative allosteric modulator (NAM) of α7 nicotinic acetylcholine receptors (α7 nAChR). With the aim to discover a non-sedating, anxiolytic compound, BNC210 was identified during phenotypic screening of a focused medicinal chemistry library using the mouse Light Dark (LD) box to evaluate anxiolytic-like activity and the mouse Open Field (OF) (dark) test to detect sedative and/or motor effects. BNC210 exhibited anxiolytic-like activity with no measurable sedative or motor effects. Electrophysiology showed that BNC210 did not induce α7 nAChR currents by itself but inhibited EC 80 agonist-evoked currents in recombinant GH4C1 cell lines stably expressing the rat or human α7 nAChR. BNC210 was not active when tested on cell lines expressing other members of the cys-loop ligand-gated ion channel family. Screening over 400 other targets did not reveal any activity for BNC210 confirming its selectivity for α7 nAChR. Oral administration of BNC210 to male mice and rats in several tests of behavior related to anxiety- and stress- related disorders, demonstrated significant reduction of these behaviors over a broad therapeutic range up to 500 times the minimum effective dose. Further testing for potential adverse effects in suitable rat and mouse tests showed that BNC210 did not produce sedation, memory and motor impairment or physical dependence, symptoms associated with current anxiolytic therapeutics. These data suggest that allosteric inhibition of α7 nAChR function may represent a differentiated approach to treating anxiety- and stress- related disorders with an improved safety profile compared to current treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors were employed by Bionomics Ltd at the time the work was done, either as full-time employees or under contract., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The in vivo fertilization process occurs in the presence of follicular fluid (FF). The aim of this study was to evaluate the effect of in vitro fertilization medium supplementation with 5% or 10% bovine follicular fluid (BFF) on the production of in vitro bovine embryos. FF was collected from ovarian follicles with a diameter of 8-10 mm, and cumulus-oocyte complexes (COCs) were co-incubated with sperm for 24 h in the commercial medium BotuFIV® (BotuPharma©), being distributed among the experimental groups: oocytes fertilized in a control medium; oocytes fertilized in a medium supplemented with 5% BFF; and oocytes fertilized in a medium supplemented with 10% BFF. After fertilization, the zygotes were cultured in vitro for 8 days. Embryo development was assessed through cleavage rates (day 2) and blastocyst formation rates (day 8). The relative expression of the genes OCT4, IFNT2, BAX, HSP70 and SOD2 was measured using the real-time polymerase chain reaction method. There was no difference (p > .05) among the different experimental groups in terms of cleavage rates and blastocyst formation rates. Regarding the gene expression results, only the blastocysts from oocytes fertilized with 10% BFF showed significantly lower expression of IFNT2 (p = .003) and SOD2 (p = .01) genes compared to blastocysts from oocytes fertilized in control medium alone, while there was no difference between blastocyst from oocytes fertilized in control medium and the ones from oocytes fertilized with 5% BFF. In addition to this, the blastocysts from oocytes fertilized with 5% BFF showed significantly reduced levels of expression of the heat shock protein HSP70 (p < .001) and the pro-apoptotic protein BAX (p = .015) compared to blastocysts from oocytes fertilized with control medium. This may indicate that lower supplementation of BFF to the IVF medium creates a more suitable environment for fertilization and is less stressful for the zygote., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Bacteriophages (phages for short) are bacteria-specific viruses that have been drawing attention when it comes to countering the ever-growing antibiotic bacterial resistance, and are being seen as one of the most promising technologies against multi-antibiotic-resistant bacteria. Although bacteriophages are commonly regarded only as anti-bacterial objects unable to directly interact with eukaryotic cell metabolism, an increasing quantity of evidence has indicated that bacteriophages can directly affect cells bacteria in both in vitro and in vivo applications, influencing the behavior of tissues and immune systems. In sight of this new range of applications, several authors have expressed enthusiasm in phage therapy as direct modulators of eukaryotic cells for clinical usage, highlighting the need for further investigations covering the pharmacology of these new "eukaryotic-viruses", as even harmful interactions with eukaryotic cells were detected after phage therapy. The present review aims to cover and highlight mechanisms through which bacteriophages may interact with immune cells, analyzing potential clinical applications and obstacles presented in the use of bacteriophages as anti-inflammatory tools.

Cashew ( Anacardium occidentale ) angular leaf spot is caused by pigmented and non-pigmented strains of Xanthomonas citri pv. anacardii , which have been isolated from infected plants in Brazil. The disease symptoms can be observed in leaves, stems, and fruits. Given that infection in young fruits results in fruits unsuitable for commercialization, angular leaf spot represents a serious threat to the cashew crop in Brazil. Here, we report the genomic sequencing of seven pigmented strains of X. citri pv. anacardii , obtained from the leaves of cashew trees from São Paulo state, Brazil, in 2009. The construction of the libraries was carried out according to the manufacturer, and whole-genome sequencing was performed using the Illumina HiSeq 2500 platform. Genome size, number of coding sequences, largest contig length, and N50 ranged from 4,996,984 to 5,003,485 bp, 4,621 to 4,643 bp, 212,513 to 362,232 bp, and 113,582 to 141,003 bp, respectively. GC content and RNA numbers were 64.68% and 54, respectively, for all strains. ANIm and d DDH analyses showed values above 99.5 and 92.1% among these strains and the non-pigmented pathotype strain of X. citri pv. anacardii (IBSBF2579 PT ). A maximum likelihood tree built with 2,708 core genes grouped all X. citri pv. anacardii strains in the same clade, with a 100% bootstrap. These resources will contribute in a relevant way to help understand the ecological, taxonomic, evolutionary, pathogenicity, and virulence aspects of X. citri pv. anacardii , which will be useful for the study and development of techniques for managing cashew angular leaf spot., Competing Interests: The author(s) declare no conflict of interest.

Changes in species distribution in response to climate change might challenge the territorial boundaries of protected areas. Amazonia is one of the global regions most at risk of developing long distances between current and future analogous climates and the emergence of climate conditions without analogs in the past. As a result, species present within the network of Protected Areas (PAs) of Amazonia may be threatened throughout the 21st century. In this study, we investigated climate velocity based on future and past climate-analogs using forward and backward directions in the network of PAs of Amazonia, in order to assess the climatic risk of these areas to climate change and verify their effectiveness in maintaining the current climate conditions. Using current (1970-2000) and future (2041-2060) average annual air temperature and precipitation data with a resolution of 10 km, climate velocities across the entire Amazon biome and average climate velocities of PAs and Indigenous Lands (ILs) were evaluated. The results show that the effects of backward velocity will be greater than that of forward velocity in the Amazon biome. However, the PA network will be less exposed to backward velocity impacts than unprotected areas (UAs)-emphasizing the importance of these areas as a conservation tool. In contrast, for the forward velocity impacts, the PA network will be slightly more exposed than UAs-indicating that the current spatial arrangement of the PA network is still not the most suitable to minimize impacts of a possible climate redistribution. In addition, a large extent of no-analog climates for backward velocities was found in central Amazonia, indicating that high temperatures and changes in precipitation patterns in this region will surpass the historical variability of the entire biome, making it a potentially isolated and unsuitable climatic envelope for species in the future. Most of the no-analog climates are in PAs, however the climate risks in ILs should also be highlighted since they presented higher climate velocities than PAs in both metrics. Our projections contrast with the median latitudinal migration rate of 2 km/year observed in most ecosystems and taxonomic groups studied so far and suggest the need for median migration rates of 7.6 km/year. Thus, despite the important role of PAs and ILs as conservation tools, they are not immune to the effects of climate change and new management strategies, specific to each area and that allow adaptation to global changes, will be necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Torres-Amaral et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.

Pilocarpus microphyllus Stapf. ex Wardlew. (Rutaceae) is an endemic and threatened medicinal plant species from tropical Brazil. Popularly known as "jaborandi", it is the unique natural source of pilocarpine, an alkaloid used to medical treat glaucoma and xerostomia. Based on Species Distribution Models (SDMs), we modeled the suitability of P. microphyllus's geographical distribution considering three Global Circulation Models (GCMs) under two future climate change scenarios (SSP2-4.5 and SSP5-8.5). The quantitative analyses carried out using ten different SDM algorithms revealed that precipitation seasonality (Bio15) and precipitation of the driest month (Bio14) were the most important bioclimatic variables. The results evidenced four main key areas of continuous occurrence of the plant spreading diagonally over tropical Brazilian biomes (Amazon, Cerrado and Caatinga). The near-future (2020 to 2040) ensemble projections considering all GCMs and scenarios have indicated negative impacts for the potential loss or significant reduction in suitable habitats for P. microphyllus in the transition region between the Amazon and Cerrado into central and northern Maranhão state, and mainly in the Caatinga biome over the northern Piaui state. On the other hand, positive impacts of the expansion of the plant habitat suitability are projected over forest cover protected areas of the Amazon biome in the southeastern Pará state. Since the jaborandi is of socioeconomic importance for many families in the north/northeast Brazil, it is urgent to implement public policies for conservation and sustainable management, thus mitigating the impacts of global climate change.

Two putative novel Burkholderia cenocepacia lineages found in the semi-arid region of north-east Brazil causing onion sour skin were studied using genomic approaches to determine their taxonomic position. Four strains belonging to one novel lineage (CCRMBC16, CCRMBC33, CCRMBC74, and CCRMBC171) and one strain (CCRMBC51) belonging to another novel lineage had their whole genome sequenced to carry out taxogenomic analyses. The phylogenomic tree built using the type (strain) genome server (TYGS) clustered the strains CCRMBC16, CCRMBC33, CCRMBC74, and CCRMBC171 into the same clade, while grouped the strain CCRMBC51 separately. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) analysis showed values above 99.21 % and 93.2 %, respectively, among the strains CCRMBC16, CCRMBC33, CCRMBC74, and CCRMBC171, while ANI and dDDH values between these strains and the strain CCRMBC51 were below 94.49 % and 56.6 %, respectively. All these strains showed ANI and dDDH values below 94.78 % and 58.8 % concerning type strains of the B. cepacia complex (Bcc) species. The phylogenetic maximum likelihood tree constructed based on the multilocus sequence analysis of core genes (cMLSA) clustered the strains CCRMBC16, CCRMBC33, CCRMBC74, and CCRMBC171 and the strain CCRMBC51 in two exclusive clades, which did not cluster with any known species of the Bcc. Therefore, combined data from TYGS, ANI, dDDH, and cMLSA demonstrated that the strains represent two novel species of the Bcc, which we classified as Burkholderia semiarida sp. nov. and Burkholderia sola sp. nov., and proposed the strains CCRMBC74 T (=IBSBF 3371  T  = CBAS 905  T ) and CCRMBC51 T (=IBSBF3370 T  = CBAS 904  T ) as type strains, respectively., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Ralstonia solanacearum species complex (RSSC) cause several phytobacteriosis in many economically important crops around the globe, especially in the tropics. In Brazil, phylotypes I and II cause bacterial wilt (BW) and are indistinguishable by classical microbiological and phytopathological methods, while Moko disease is caused only by phylotype II strains. Type III effectors of RSSC (Rips) are key molecular actors regarding pathogenesis and are associated with specificity to some hosts. In this study, we sequenced and characterized 14 newly RSSC isolates from Brazil's Northern and Northeastern regions, including BW and Moko ecotypes. Virulence and resistance sequences were annotated, and the Rips repertoire was predicted. Confirming previous studies, RSSC pangenome is open as α≅0.77. Genomic information regarding these isolates matches those for R. solanacearum in NCBI. All of them fit in phylotype II with a similarity above 96%, with five isolates in phylotype IIB and nine in phylotype IIA. Almost all R. solanacearum genomes in NCBI are actually from other species in RSSC. Rips repertoire of Moko IIB was more homogeneous, except for isolate B4, which presented ten non-shared Rips. Rips repertoire of phylotype IIA was more diverse in both Moko and BW, with 43 common shared Rips among all 14 isolates. New BW isolates shared more Rips with Moko IIA and Moko IIB than with other public BW genome isolates from Brazil. Rips not shared with other isolates might contribute to individual virulence, but commonly shared Rips are good avirulence candidates. The high number of Rips shared by new Moko and BW isolates suggests they are actually Moko isolates infecting solanaceous hosts. Finally, infection assays and Rips expression on different hosts are needed to better elucidate the association between Rips repertoire and host specificities.

Background: In several countries, the leaf juice of Agave sisalana (also known as sisal) is widely used topically, especially as an antiseptic, and orally for the treatment of different pathologies. However, in Brazil, which is the largest producer of Agave sisalana, its residue, which represents the majority of its weight, has been thrown away. For this reason, the determination of the pharmacological and toxicological potentials of sisal residue and its possible therapeutic use is seen as a way to contribute to the sustainable development and social promotion of the largest producer of sisal in Brazil, the interior of Bahia State, which is among the poorest areas in the country. Given the scarcity of available scientific studies on the pharmacological and toxicological properties of sisal residue juice, this study aimed to promote the acid hydrolysis of this juice to potentiate the anti-inflammatory effect already described in the literature. Furthermore, it aimed to evaluate the toxicological profile of the hydrolyzed extract (EAH) and to determine its acute toxicity, as well as its side effects on the reproductive aspects of rats., Method: The anti-inflammatory effect of EAH was evaluated in vitro using the induction of hemolysis by hypotonic solution and in vivo in rats using the carrageenan-induced paw edema test and the xylene-induced ear edema test. The acute toxicity, resulting from a single-dose administration, was investigated for some manifestation of toxic symptoms related to motor control and consciousness in rats. At a concentration of 100 mg/kg, by repeated doses, the reproductive toxicity effects of EAH in rats were assessed., Results: In vitro anti-inflammatory activity was positive using the human red blood cell membrane stabilization method. In both in vivo tests used to assess the anti-inflammatory activity, EAH (at three doses) significantly inhibited edema when compared to the control group. At a dose of 50 mg/kg, EAH exhibited a greater effect than indomethacin, a nonsteroidal anti-inflammatory drug with known activity. In vivo toxicological studies have shown that EAH does not present toxic effects when administered orally in a single dose, up to 1000 mg/kg. Finally, EAH promoted a gonadotoxic effect and increased the embryonic mortality rate after implantation., Conclusions: It is suggested that the anti-edematogenic effect of the acid hydrolysis extract from sisal juice is due to the high concentration of steroidal sapogenins. Therefore, this extract can be considered a potential new anti-inflammatory or even an important sapogenin source for the development of steroidal glucocorticoids. However, further studies are needed to elucidate the chemical composition of sisal juice. Regarding toxicology studies, EAH did not show cytotoxic and clastogenic potentials, but it presented a powerful reproductive toxic effect in rats.

The oceanic South Atlantic Convergence Zone (SACZ) has played a major role during South America's 2021/2022 summer extreme rainy season, being responsible for more than 90% of the precipitation in some regions of Southeast Brazil and in some regions of the Southwestern Atlantic Ocean (SWA). The summer of 2021/2022 was unique and rare and considered an abnormally humid season as verified by official Brazilian Institutes. First, the unusual number of cases of SACZ episodes (seven), was the highest recorded in the last decade. Second, all the cases that occurred were oceanic SACZ that assumed characteristics of an Atmospheric River and produced an excessively anomalous amount of precipitation during this period. Excess precipitation along with the regions located in mountainous and very uneven relief, which by orographic effects favors high precipitation volumes, were responsible for amplifying the observed impacts, such as landslides and floods that caused several losses to society. We also showed the main effects of coupling and interaction between the waters of the surface layer of the SWA and the atmosphere. Our learning from this study ends with the unprecedented results of how the marine atmospheric boundary layer (MABL) is locally modulated by the sea surface temperature (SST) that lies just below it. Until the present moment, we emphasize that this important mechanism has not been widely highlighted in the literature, showing that even though the ocean is colder than before oceanic SACZ is established, it is still warmer than the overlying air, thus, the ocean continues to be an active source of heat and moisture for the atmosphere and enhances the MABL instability process., (© 2023. The Author(s).)

This study investigated the chemical composition and evaluated the antibacterial and antibiofilm activities of essential oils (EOs) extracted from Ruellia asperula (EORA) and Ruellia paniculata (EORP) against oral streptococci. The EO constituents were analyzed by gas chromatography/mass spectrometry. The antimicrobial potential of EOs was evaluated using the minimum inhibitory concentration, minimum bactericidal concentration, and time-kill determination. Furthermore, the quantification of total biomass and the number of viable cells in the biofilms were evaluated. The major constituents of EORA were cariophylla-4(12)-8-(13)-dien-5β-ol (14.1%), (β)-caryophyllene (22.7%), and caryophyllene oxide (29.4%). For EORP, the major constituents were (β)-caryophyllene (11.0%), spathulenol (13.1%), and δ-amorphene (14.9%). The tested EOs exhibited antibacterial activity against planktonic growth and biofilm formation. Thus, the EOs from R. asperula and R. paniculata prove to be promising alternatives for bacterial growth control and biofilm formation prevention of oral streptococci.

Banana tree bacterial wilt is caused by the Ralstonia solanacearum Moko ecotype. These strains vary in their symptom progression in banana, and are classified as typical Moko variants (phylotype IIA and IIB strains from across Central and South America), Bugtok variant (Philippines), and Sergipe facies (the states of Sergipe and Alagoas, Brazil). This study used comparative genomic and phylogenomic approaches to identify a correlation between the symptom progression of the Moko ecotypes based on the analysis of 23 available genomes. Average nucleotide identity and in silico DNA-DNA hybridization revealed a high correlation (>96% and >78%, respectively) between the genomes of Moko variants. Pan-genome analysis identified 21.3% of inheritable regions between representatives of the typical Moko and Sergipe facies variants, which could be traced to an abundance of exclusive homolog clusters. Moko ecotype genomes shared 1,951 orthologous genes, but representatives with typical symptoms did not display unique orthologues. Moreover, Bugtok disease and Sergipe facies genomes did not share any unique genes, suggesting convergent evolution to a shared symptom progression. Overall, genomic and phylogenomic analyses were insufficient to differentiate the Moko variants based on symptom progression.

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.

The Burkholderia genus has high ecological and nutritional versatility, having species capable of causing diseases in animals, humans, and plants. During chronic infections in humans, biofilm formation is a characteristic often associated with strains from different species of this genus. However, there is still no information on the formation of biofilms by plant pathogenic strains of B. cenocepacia (Bce) lineages IIIA and IIIB and B. gladioli pv. alliicola (Bga), which are associated with onion bacterial scale rot in the semi-arid region of northeast Brazil. In this study, we performed an in vitro characterization of biofilm formation ability in different culture media by the phytopathogenic strains of Bce and Bga and investigated its relationship with swarming motility. Our results indicated the existence of an intraspecific variation in biofilm formation capacity in vitro by these bacteria and the existence of a negative correlation between swarming motility and biofilm formation for strains of Bce lineage IIIB. In addition, histopathological analyses performed using optical microscopy and scanning electron microscopy revealed the formation of biofilm in vivo by Bce strains in onion tissues., (© 2021. Sociedade Brasileira de Microbiologia.)

Bacteriophages are bacterial-specific viruses and the most abundant biological form on Earth. Each bacterial species possesses one or multiple bacteriophages and the specificity of infection makes them a promising alternative for bacterial control and environmental safety, as a biotechnological tool against pathogenic bacteria, including those resistant to antibiotics. This application can be either directly into foods and food-related environments as biocontrol agents of biofilm formation. In addition, bacteriophages are used for microbial source-tracking and as fecal indicators. The present review will focus on the uses of bacteriophages like bacterial control tools, environmental safety indicators as well as on their contribution to bacterial control in human, animal, and environmental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rogovski, Cadamuro, da Silva, de Souza, Bonatto, Viancelli, Michelon, Elmahdy, Treichel, Rodríguez-Lázaro and Fongaro.)

We present new constraints on dark matter interactions using 1.7 years of COSINE-100 data. The COSINE-100 experiment, consisting of 106 kg of tallium-doped sodium iodide [NaI(Tl)] target material, is aimed to test DAMA’s claim of dark matter observation using the same NaI(Tl) detectors. Improved event selection requirements, a more precise understanding of the detector background, and the use of a larger dataset considerably enhance the COSINE-100 sensitivity for dark matter detection. No signal consistent with the dark matter interaction is identified and rules out model-dependent dark matter interpretations of the DAMA signals in the specific context of standard halo model with the same NaI(Tl) target for various interaction hypotheses.

Reverse transcription-quantitative PCR (RT-qPCR) is an analytical tool for gene expression quantification. Reference genes are not yet available for gene expression analysis during interactions of Ralstonia solanacearum with 'Hawaii 7996' (the most stable source of resistance in tomato). Here, we carried out a multi-algorithm stability analysis of eight candidate reference genes during interactions of 'Hawaii 7996' with one incompatible/avirulent and two compatible/virulent (= resistance-breaking) bacterial isolates. Samples were taken at 24- and 96-h post-inoculation (HPI). Analyses were performed using the ∆∆Ct method and expression stability was estimated using BestKeeper, NormFinder, and geNorm algorithms. TIP41 and EF1α (with geNorm), TIP41 and ACT (with NormFinder), and UBI3 and TIP41 (with BestKeeper), were the best combinations for mRNA normalization in incompatible interactions at 24 HPI and 96 HPI. The most stable genes in global compatible and incompatible interactions at 24 HPI and 96 HPI were PDS and TIP41 (with geNorm), TIP41 and ACT (with NormFinder), and UBI3 and PDS/EXP (with BestKeeper). Global analyses on the basis of the three algorithms across 20 R. solanacearum-tomato experimental conditions identified UBI3, TIP41 and ACT as the best choices as reference tomato genes in this important pathosystem., (© 2021. The Author(s).)

We report the use of bacteriophages for control of Salmonella Enteritidis in poultry production. Phage was isolated by the double-agar plate assay from agricultural waste samples, and one isolate, named SM1, was selected and propagated for application in poultry litter. Two experimental protocols were tested: single treatment and repeated treatment (re-application of phage SM1 after 6 h and 12 h). Each treatment cycle involved 25 g of poultry litter placed in plastic boxes and contaminated with 10 5 Colony Forming Units mL -1 (CFU mL -1 ) of S. Enteritidis, in independent duplicates. The contaminated litter was treated with 10 6 Plaque Forming Units mL -1 (PFU mL -1 ) of SM1 phage by dripping. Repeated application of phage SM1 reduced Salmonella counts by over 99.9%; the phage persisted in poultry litter for over 35 days. This study illustrates the application of SM1 treatment as a promising technology for bacterial control in production matrices that could allow safe and sustainable use of agricultural waste products as biofertilizers.

Sex selection through sperm sorting offers advantages in regards selection pressure in high-producing livestock. However, the sex-sorting process results in sperm membrane and DNA damage that ultimately decrease fertility. We hypothesized that given the role of protamines in DNA packaging, protamine deficiency could account, at least partially, for the DNA damage observed following sperm sex sorting. To test this, we compared protamine status between unsexed and sexed spermatozoa from two bulls using the fluorochrome chromomycin A3 (CMA3) and flow cytometry. Then, we assessed embryo development following in vitro fertilization (IVF) using the same sperm treatments. Overall, sperm protamination was not different between sexed and unsexed semen. However, one of the two bulls displayed higher rates of protamine deficiency for both unsexed and sexed semen (P < 0.05). Moreover, unsexed semen from this bull yielded lower blastocyst (P < 0.05) and blastocyst hatching rates than unsexed sperm from the other bull. CMA3-positive staining was negatively correlated with cleavage (R2 85.1, P = 0.003) and blastocyst hatching (R2 87.6, P = 0.006) rates in unsexed semen. In conclusion, while the sex-sorting process had no effect on sperm protamine content, we observed a bull effect for sperm protamination, which correlated to embryo development rates following IVF.

Citrus canker caused by Xanthomonas citri subsp. citri is one of the most important citrus diseases in the world (Gottwald et al. 2002), mainly for citrus-producing countries with humid sub-tropical regions such as United States, Argentina, and Brazil, where losses may be significant (Behlau et al. 2020). In the state of Rio Grande do Norte (RN), Brazil, citrus production is expanding and shows social and economic importance for small farmers, which produced approximately 297 tons of lime in this state in 2019 (IBGE 2021). In December 2019, we observed symptoms of erumpent lesions with margins surrounded by yellow haloes on leaves and fruit of the lime ( Citrus aurantifolia cv. 'Galego') (about 5% incidence) in a plantation located in the municipality of Mossoró, RN (05°12'21.1"S, 37°19'16"W). Samples were collected from the lime orchard, and five bacterial strains (CCRMXC01 to CCRMXC05) showing yellow, convex, mucoid colonies were isolated in a nutrient-yeast-dextrose-agar medium (NYDA). Pathogenicity tests were performed on sweet orange ( C. sinensis cv. 'Pêra') and lime ( C. latifolia cv. 'Tahiti') seedlings. Four wounds per leaf (upper side) were carried out with an entomological pin and 10 µl of a bacterial suspension (108 CFU mL -1 ) were deposited on each wound. The negative control consisted of leaves treated with sterile distilled water (SDW). For each citrus species, we used four replicates per strain and one leaf with four wounds per replicate. Inoculated leaves developed erumpent lesions with margins surrounded by yellow haloes six days after inoculation (DAI) in both citrus species, while leaves treated with SDW remained symptomless. Nine DAI, we reisolated the pathogen and performed rep-PCR (REP, ERIC, and BOX-PCR) analyses (Gama et al. 2018) with the strains inoculated and reisolated to confirm the identity of the strains and to fulfill Koch's postulates. The strains were stored at the Culture Collection Rosa Mariano (CCRM) of the Phytobacteriology Laboratory at the Universidade Federal Rural de Pernambuco. The five strains reisolated showed the same REP, ERIC, and BOX-PCR profiles as the strains used for inoculations. The molecular identification was performed sequencing the dnaK , fyuA , gyrB , and rpoD genes (Young et al. 2008). Each fragment was sequenced in both the forward and reverse directions. Using the BLASTn tool, we observed that sequences of the dnaK (GenBank MW218913 to MW218917), fyuA (GenBank MW218918 to MW218922), and rpoD (GenBank MW218928 to MW218932) genes of the strains CCRMXC01 to CCRMXC05 showed 100% of identity with the sequences of these genes from the type strain (ICMP 24 T ) and of other strains of X. citri subsp. citri (ICMP 21 and ICMP 7493), while sequences of gryB (GenBank MW218923 to MW218927) of the former strains showed 100% identity with the gyrB sequence of the strains ICMP 24 T and ICMP 7493 and 99,85% identity with strain ICMP 21. This short variation in the sequence of the gyrB gene also may be observed among strains of X. citri subsp. citri available in NCBI database (https://www.ncbi.nlm.nih.gov/). The phylogenetic analysis performed using Bayesian inference and the concatenated sequence of all the type or representative strains of species and pathovars of Xanthomonas available in GenBank showed that the strains CCRMXC01 to CCRMXC05 clustered together with strain ICMP 24 T with 1.0 posterior probability. To our information, this is the first report of X. citri subsp. citri causing citrus canker on lime in RN state, Brazil.

Heat stress reduces the reproductive capacity of bulls raised in tropical climate. However, the reestablishment of scrotal thermoregulation and the dynamics of sperm defects emergence after stress are not completely known in buffaloes. Thus, the study aimed to evaluate the effect of short-term heat stress over scrotal thermoregulation and sperm attributes, relating them to spermatogenesis stages. Five buffalo bulls went through scrotal insulation during 48 h (from day 0 to day 2). Semen samples were collected every 7 days (from day -7 to day 49) and analyzed about the progressive motility, viability, and sperm morphology. Heat stress significantly destabilized scrotal thermoregulation (P < 0.001). Scrotal temperature was from 4.2 to 6.3 °C lower than the core body temperature, except on insulation days (P < 0.001), and returned to the basal condition five days after the removal of the stressing stimulus. More significant deleterious effects were observed in sperm morphology than in cell concentration, motility, and viability. The chronology of morphologic defects expression demonstrated tail defects (days 7-14), cytoplasmic droplets (days 14-28), and head defects (day 28), returning to pre-insulation condition 35 days after the thermal challenge. Thus, hyperthermia harmed more intensely spermatozoa in epididymal transit, elongated spermatids, and secondary spermatocytes. It is concluded that water buffalo bulls present a peculiar manifestation of sperm morphology after short-term stress, indicating an important difference related to the bovine species. Therefore, during the andrological evaluation of buffalo bulls, it is necessary to avoid the allometric extrapolation between these species., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Banana vascular wilt or Moko is a disease caused by Ralstonia solanacearum. This study aimed to sequence, assemble, annotate, and compare the genomes of R. solanacearum Moko ecotypes of different sequevar strains from Brazil. Average nucleotide identity analyses demonstrated a high correlation (> 96%) between the genome sequences of strains CCRMRs277 (sequevar IIA-24), CCRMRs287 (IIB-4), CCRMRs304 (IIA-24), and CCRMRsB7 (IIB-25), which were grouped into phylotypes IIA and IIB. The number of coding sequences present in chromosomes and megaplasmids varied from 3,070 to 3,521 and 1,669 to 1,750, respectively. Pangenome analysis identified 3,378 clusters in the chromosomes, of which 2,604 were shared by all four analyzed genomes and 2,580 were single copies. In megaplasmids, 1,834 clusters were identified, of which 1,005 were shared by all four genomes and 992 were identified as single copies. Strains CCRMRsB7 and CCRMRs287 differed from the others by having unique clusters in both their chromosomes and megaplasmids, and CCRMRsB7 possessed the largest genome among all Moko ecotype strains sequenced to date. Therefore, the genomic information obtained in this study provides a theoretical basis for the identification, characterization, and phylogenetic analysis of R. solanacearum Moko ecotypes.

Hepatitis E virus (HEV) is an important enteric agent that can circulate in swine; it is excreted in manure, and of zoonotic interest. The present study investigated, by RT-qPCR, the circulation of HEV in swine manure from different types of pig farms (maternity, nursery, and grow-finish farms) in Santa Catarina State, the major pig production area of Brazil, and also evaluated the HEV removal efficiency of psychrophilic anaerobic biodigesters (PABs). While HEV was consistently detected in manure from grow-finish pig farms (>4 log HEV genome copies (GC) L -1 ), the virus was not detected in manure from maternity and nursery farms. These findings suggest a potential high biosafety status during primary-swine production, with a subsequent contamination in grow-finish production. The anaerobic biodigestion process reduced more than 2 log 10 HEV GC in the processed swine manure. However, the virus concentration in final effluent remained high, with an average value of 3.85 log 10 HEV GC L -1 . Consequently, our results demonstrate that PABs can be a robust tool for effective inactivation of HEV, while reinforcing the need for sanitary surveillance and legislation of swine manure-derived biofertilizers, to avoid the spread of zoonotic enteric pathogens such as HEV.

Emerging contaminants (ECs) include endocrine-disrupting compounds, pharmaceuticals (lipid regulators, antibiotics, diuretics, non-steroid anti-inflammatory drugs, stimulant drugs, antiseptics, analgesic, beta blockers), detergents, disinfectants, and personal care products. The residues from these compounds have become a concerning because of their bioactive presence on environmental matrices, especially water bodies. The development of technologies, aiming the secure and efficient removal of these compounds from the environment or event to remove them before they achieve the environment, is necessary. In these context, the present review is about promising eco-friendly, low-cost and specially applied, including biological processes using microalgae, bacteria, enzymes produced by fungi, and adsorbent materials such as those recycled from other processes waste. The processes where revised considering the removal mechanism and the efficiency rate.

Ralstonia solanacearum is the causal agent of Moko disease in bananas, which in the state of Sergipe in northeastern Brazil causes "Sergipe facies". This disease induces atypical symptoms similar to those of Bugtok disease in the Philippines. This study was conducted to sequence, assemble, and annotate the genomes of the Sergipe facies-causing isolates SFC and IBSBF2570 (sequevar IIA-53) and compare their genomes with two representative isolates causing Bugtok disease. The genomes were sequenced and assembled, resulting in lengths of 5.58 Mb (SFC) and 5.46 Mb (IBSBF2570) in 185 and 174 contigs, respectively. The isolates of Sergipe facies and Bugtok disease showed similarities in their gene contents. We identified 5,668 information clusters, 3,752 of which were shared by all genomes (core genes). Moreover, 3,585 single-copy genes were identified. Isolates causing Bugtok disease exclusively shared 266 more information clusters than the isolates causing Sergipe facies. These results suggest that Sergipe facies and Bugtok disease isolates show high genomic similarity. However, the similarity is even greater between the Bugtok disease isolates. This may be because of their longer period of interaction compared to Sergipe facies isolates.

Since the discovery of the double helix and the introduction of genetic engineering, the possibility to develop new strategies to manipulate the genome has fascinated scientists around the world. Currently scientists have the knowledge andabilitytoedit the genomes. Several methodologies of gene editing have been established, all of them working like "scissor", creating double strand breaks at specific spots. The introduction of a new technology, which was adapted from the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas bacterial immune system, has revolutionized the genetic therapy field, as it allows a much more precise editing of gene than the previously described tools and, therefore, to prevent and treat disease in humans. This review aims to revisit the genome editing history that led to the rediscovery of the CRISPR/Cas technology and to explore the technical aspects, applications and perspectives of this fascinating, powerful, precise, simpler and cheaper technology in different fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)