•Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor that is overexpressed in the blast crisis of chronic myeloid leukemia (CML).•CML cell lines transfected with the BCR-ABL1 ...oncogene show increased PAR1 expression.•Inhibition of PAR1 reduces BCR-ABL1 and vascular endothelial growth factor (VEGF) expression in CML cell lines.•A decreased PAR1 expression is observed in tyrosine kinase inhibitor (TKI)-responsive CML patients.•TKI-resistant CML patients exhibit increased PAR1 levels.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which generates the oncogene BCR-ABL1. Protease-activated receptor 1 (PAR1) is involved in tumor progression and angiogenesis. We have previously reported that PAR1 expression is elevated in human leukemias that display a more aggressive clinical behavior, including the blast crisis of CML. In this study, we analyzed the crosstalk between the oncoprotein BCR-ABL and PAR1 in CML. Leukemic cell lines transfected with the BCR-ABL1 oncogene showed significantly higher expression levels of PAR1 compared with that of wild-type counterparts. This phenomenon was reversed by treatment with tyrosine kinase inhibitors (TKIs). Conversely, treatment with the PAR1 antagonist SCH79797 inhibited BCR-ABL expression. The PAR1 antagonist induced apoptosis in a dose- and time-dependent manner. Higher vascular endothelial growth factor (VEGF) levels were observed in cells transfected with BCR-ABL1 than in their wild-type counterparts. VEGF expression was strongly inhibited after treatment with either TKIs or the PAR1 antagonist. Finally, we evaluated PAR1 expression in CML patients who were either in the blast or chronic phases and had either received TKI treatment or no treatment. A significant decrease in PAR1 expression was observed in treatment-responsive patients, as opposed to a significant increase in PAR1 expression levels in treatment-resistant patients. Patients classified as high risk according to the Sokal index showed higher PAR1 expression levels. Our results demonstrate the crosstalk between BCR-ABL and PAR1. These data may offer important insight into the development of new therapeutic strategies for CML.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the ...largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in São Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality.
Cytogenetic studies in Neotropical electric knifefish of genus Gymnotus have shown a remarkable interspecific variability, including distinct sex chromosome systems. In this study, we present the ...first chromosomal data in Gymnotus bahianus from Contas River basin, northeastern South America. Based on extensive analyses, the modal diploid values were 2n = 36 (30m/sm + 6st) for females and 2n = 37 (32m/sm + 5st) for males. Therefore, a novel XX/XY1Y2 sex chromosome system is described for the genus. Single nucleolar organizer regions (NORs) interspersed to GC-rich sites were detected on a subtelocentric pair (7th) for both sexes and confirmed by fluorescent in situ hybridization with 18S rDNA probes. Heterochromatin was detected at pericentromeric regions of all chromosomes and interspersed to NORs on pair 7 and 5S rDNA cistrons on pair 9. The highly differentiated karyotype of Gymnoytus bahianus, with low diploid numbers and a unique XX/XY1Y2 system, reinforces the independent origin of sex chromosomes in Gymnotiformes and seems to reflect the particular evolutionary history of this species in a small and isolated drainage system. Moreover, in spite of morphological similarities, the present results indicate a remarkable chromosomal divergence in relation to closely related species such as G. sylvius and G. carapo.
Seabirds are marine predators known to forage in association with fisheries, however detailed knowledge on seabird-fishery interactions remains scarce in several regions of the world. We quantified ...seabird-fishery interactions and bycatch in central Portuguese coastal waters (NE Atlantic) between 2016 and 2018 in four gears: purse-seines, longlines, gillnets, and fishing traps. We mapped gear-specific fishing effort and seabird bycatch events and characterized fishery catches. Specific objectives were to determine separately for seabird-fishery interactions and bycatch (i) the gear with the highest rates, (ii) the most abundant species, and (iii) to assess the main drivers (i.e. year, season, gear, and fishery catch) of seabird-fishery interactions. Purse-seines had the highest seabird-fishery interactions, and the most abundant species were Yellow-legged and Lesser black-backed gulls, Northern gannet, and Cory's shearwater. Total seabird-fishery interactions varied inter-annually but not seasonally, indicating high total seabird numbers at fishing boats year-round. In contrast, higher fishery interactions were found during spring for Yellow-legged gulls. Age classes of individuals varied according to species, and fishery catches had a positive effect on seabird-fishery interactions. Seabird bycatch occurred mostly in longlines and within the ‘Ilhas Berlengas’ Special Protection Area. Northern gannet and Cory's shearwater were the most bycaught species, and species ecological traits seemed important in determining gear-specific bycatch. Our results suggest a strong influence of purse-seine and artisanal fisheries on seabirds in the NE Atlantic coast, and future studies should investigate the effects of these fisheries on seabird populations in other regions of the world.
•Purse-seine had the highest seabird-fishery interactions.•Longline had the highest seabird bycatch rate.•Yellow-legged and Lesser black-backed gulls interacted more with fisheries.•Northern gannet and Cory's shearwater were the most bycaught seabird species.•Purse-seine and artisanal fisheries influence seabirds in the NE Atlantic coast.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Taxonomic identification of food is a key component to the correct implementation of traceability pipelines during fish processing. Genetic methods have increased exponentially our discrimination ...power at the species level. In this context, sustainable management of tuna fisheries can clearly profit from the implementation of this kind of quality control procedures, although they are more difficult to implement at the earlier stages of tuna processing, from harvest to the arrival of fish landings at a processing plant. Here we provide a case study using tuna landings to a processing plant in Cabo Verde, an important small island developing State, which supplies mainly the European Union region. Using DNA sequencing based species identification of tissue samples, we found a taxonomic miss-assignment of species identity in 33% of the individuals in the three target tuna species, Bigeye (Thunus obesus), Yellowfin (Thunus albacares), and Skipjack (Katsuwonus pelamis). More than half of Yellowfin samples were wrongly assigned as bigeyes or skipjacks. We also found that many bigeyes were wrongly assigned as yellowfins or skipjacks. None of the skipjacks were incorrectly assigned. The proportion of Yellowfin samples incorrectly assigned as bigeye was significantly higher than the samples of bigeye incorrectly assigned as yellowfins. These results clearly prove the need for improved traceability processes, which should encompass the whole processing pipeline, from harvesting to the consumer.
•DNA sequencing found issues of species traceability on tuna landings in Cabo Verde.•Miss-assignment of species identity occurred in 33% of the tuna individuals.•Miss-assignment did not occur in Skipjack tunas, only in Yellowfin and Bigeye tunas.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The piezoelectric and pyroelectric properties of electrospun polyethylene oxide nanofibres embedded with polar amino acids DL-alanine and L-lysine hemihydrate are reported. A high pyroelectric ...coefficient of 150 C m−2 K−1 was measured for L-lysine hemihydrate and piezoelectric current densities up to 7 A m−2 were obtained for the nanofibres. The study reveals a potential for polymer amino-acid nanofibres to be used as biocompatible energy harvesters for autonomous circuit applications like in implantable electronics.
Clinical studies have shown antineoplastic effectiveness of monoclonal antibodies (MAbs) against EGFR for different indications. Several MAbs directed to EGFR were developed recently, such as ...matuzumab, but there is still lack of information on preclinical data on its combination with chemo-radiation. Thus, the present study intended to examine the molecular pathways triggered by matuzumab alone or associated to chemo-radiotherapy in gynecological cell lines and its impact on cell growth and signaling.
Combination of matuzumab with radiation and cisplatin did not enhance its cytostatic effects on A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in clonogenic assays, when compared to controls. The lack of effect was mediated by persistent signaling through EGFR due to its impaired degradation. In spite of the fact that matuzumab inhibited phosphorylation of EGFR, it had no effect upon cell viability. To analyze which downstream molecules would be involved in the EGFR signaling in the presence of matuzumab, we have tested it in combination with either PD98059 (MAPK inhibitor), or LY294002 (PI3K inhibitor). Matuzumab exhibited a synergic effect with LY294002, leading to a reduction of Akt phosphorylation that was followed by a decrease in A431 and Caski cells survival. The combination of PD98059 and matuzumab did not show the same effect suggesting that PI3K is an important effector of EGFR signaling in matuzumab-treated cells. Nonetheless, matuzumab induced ADCC in Caski cells, but not in the C33A cell line, suggesting that its potential therapeutic effects in vitro are indeed dependent on EGFR expression.
Matuzumab combined with chemoradiation did not induce cytotoxic effects on gynecological cancer cell lines in vitro, most likely due to impaired EGFR degradation. However, a combination of matuzumab and PI3K inhibitor synergistically inhibited pAkt and cell survival, suggesting that the use of PI3K/Akt inhibitors could overcome intrinsic resistance to matuzumab in vitro. Altogether, data presented here can pave the way to a rational design of clinical strategies in patients with resistant profile to anti-EGFR inhibitors based on combination therapy.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Studies on sex-specific segregation in foraging behaviour and trophic niche have been focussed on large and dimorphic seabirds, with less information on small monomorphic species. Here, we used ...mini-GPS loggers, habitat suitability models, and stable isotopes to assess sex differences in the foraging movements, spatial distribution, and trophic ecology of Boyd’s shearwaters
Puffinus lherminieri boydi
in Raso Islet (16°36’ N, 24°35’ W), Cabo Verde, during the chick-rearing periods of 2018–2019. The existence of sexual foraging segregation was tested in short (< 1 day) and in long trips (≥ 1 day). Females engaged in slightly longer and more distant foraging trips, reaching northerly regions when compared to males, although sex differences were more pronounced during short trips. Spatial overlap within and between sexes was low, indicating a sex-specific pattern, albeit slight, in the foraging behaviour and spatial distribution of adult breeders. Habitat suitability models revealed a higher contribution of sea surface temperature and height for short and long trips, respectively, and regardless of sex. Stable isotope analysis revealed that both sexes occupied similar isotopic niches and the mixing model revealed no diet differences. In the absence of sexual size dimorphism, these findings may indicate that differential energetic demands may not manifest in strong differences in foraging behaviour or prey preferences, however, may be perceptible in differences in provisioning behaviour. Thus, it is possible that other factors involving distinct parental investment in chick-provisioning, such as the sensitivity to chick begging, could help explain the occurrence of sexual segregation in Boyd’s shearwater.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The lateral periodontal cyst, as the name implies, occurs on a lateral periodontal location and is of developmental origin, arising from cystic degeneration of clear cells of the dental lamina. A ...botryoid odontogenic cyst is considered to be a rare multilocular variant of a lateral periodontal cyst.
We report the clinical and histopathologic features of a rare case of botryoid odontogenic cyst found in an edentulous area corresponding to the right lower canine of a 64-year-old African-American woman. A multilocular radiolucency was observed, and surgical removal of the lesion revealed a nodule of rubber-like consistency measuring about 1.5 cm in diameter. Cross-sectioning of the nodule showed that it consisted of various cystic compartments. Histologically, various voluminous periodic acid-Schiff-negative clear cells randomly distributed throughout the cystic epithelium were observed, as well as cell layers showing thickenings generally formed by oval, sometimes entangled plaques. The capsule consisted of fibrous connective tissue and showed rare and discrete foci of a perivascular mononuclear inflammatory infiltrate and reactive bone-tissue fragments. The final diagnosis was botryoid odontogenic cyst.
We provide data that allow the reader to establish the differences between botryoid odontogenic cyst, glandular odontogenic cyst, and lateral periodontal cyst, helping with the differential diagnosis. The reader will have the opportunity to review botryoid odontogenic cyst clinical and histopathologic features, including treatment.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Amidst unprecedented anthropogenic pressure on marine ecosystems, seabirds can serve as sentinels for shifts in marine prey availability. We examined the diet and foraging ecology of 2 sympatric ...Procellariiformes, the Cape Verde shearwater
Calonectris edwardsii
and Bulwer’s petrel
Bulweria bulwerii
, during their breeding period in Cabo Verde, West Africa. By analysing fatty acids (FAs), δ
15
N and δ
13
C values, and using GPS loggers, we quantitatively assessed the diet of both adults and chicks, estimated the isotopic niche of adult birds, and identified their main foraging regions. Our findings revealed annual variations in the diet of both adults and chicks, supported by quantitative prey estimates and FA signatures. Adult Cape Verde shearwaters consistently displayed a diet enriched in commercial fishes (>40%), with varying proportions of squid or non-commercial fishes across different years. Bulwer’s petrel displayed greater diet variability, consuming higher proportions of squid (54%), mesopelagic fishes (81%), and commercial fishes (29%) in 2017, 2018, and 2019, respectively. Chicks of both species exhibited varying diets across years. However, chick growth and fledging parameters remained fairly consistent among years. The isotopic niche, GPS tracking, and oceanographic conditions within foraging regions provided partial support for the annual variations observed in the diet of adults, especially for Cape Verde shearwaters. However, the diet differences for Bulwer’s petrels were less straightforward, likely due to the equitable distribution of their main prey. Notably, both species exhibited resilience in coping with unfavourable foraging conditions, enabling adult breeders to exploit a wide variety of prey resources without compromising breeding outcomes.
PDF
