Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor,partially overlapping but distinct from the EGF-binding epitope

Decorin, a small leucine-rich proteoglycan, is a key regulator of tumor growth by acting as an antagonist of the epidermal growth factor receptor (EGFR) tyrosine kinase. To search for cell surface receptors interacting with decorin, we generated a decorin/alkaline phosphatase chimeric protein and used it to screen a cDNA library by expression cloning. We identified two strongly reactive clones that encoded either the full-length EGFR or its ectodomain. A physiologically relevant interaction between decorin and EGFR was confirmed in the yeast two-hybrid system and further validated by experiments using EGF/EGFR interaction and transient cell transfection assays. Using a panel of deletion mutants, decorin binding was mapped to a narrow region of the EGFR within its ligand-binding L2 domain. Moreover, the central leucine-rich repeat 6 of decorin was required for interaction with the EGFR. Site-directed mutagenesis of the EGFR L2 domain showed that a cluster of residues, His(394)-Ile(402), was essential for both decorin and EGF binding. In contrast, K465, previously shown to be cross-linked to epidermal growth factor (EGF), was required for EGF but not for decorin binding. Thus, decorin binds to a discrete region of the EGFR, partially overlapping with but distinct from the EGF-binding domain. These findings could lead to the generation of protein mimetics capable of suppressing EGFR function.     

Biomass change in an Atlantic tropical moist forest: the ENSO effect in permanent sample plots over a 22-year period

There are a number of controversies surrounding both biomass estimation and carbon balance in tropical forests. Here we use long-term (from 1978 through 2000) data from five 0.5-ha permanent sample plots (PSPs) within a large tract of relatively undisturbed Atlantic moist forest in southeastern Brazil to quantify the biomass increment (M_I), and change in total stand biomass (M_stand), from mortality, recruitment, and growth data for trees 10 cm diameter at breast height (DBH). Despite receiving an average of only 1,200 mm annual precipitation, total forests biomass (334.5±11.3 Mg ha^–1) was comparable to moist tropical forests with much greater precipitation. Over this relatively long-term study, forest biomass experienced rapid declines associated with El Niño events, followed by gradual biomass accumulation. Over short time intervals that overlook extreme events, these dynamics can be misinterpreted as net biomass accumulation. However for the 22 years of this study, there was a small reduction in forest biomass, averaging –1.2 Mg ha^–1 year^–1 (±3.1). Strong climatic disturbances can severely reduce forest biomass, and if the frequency and intensity of these events increases beyond historical averages, these changing disturbance regimes have the capacity to significantly reduce forest biomass, resulting in a net source of carbon to the atmosphere.     

Impact of COVID-19 on the curative treatment of prostate cancer: a national cross-sectional study

BackgroundCOVID-19 pandemic affected access to cancer treatment worldwide. However, there is a lack of data about the impact in developing countries. The objective was to evaluate COVID-19 impact on curative prostate cancer (Pca) treatment in Brazil.Materials and methodsWith data extracted from the Brazilian Ministry of Health database, the Non-COVID and COVID periods were analyzed to compare the absolute number of radical prostatectomy (RP) and radiotherapy (RT) executed in the country and regions.ResultsWith data from 50,169 Pca patients (Non-COVID = 28,106 cases and COVID = 22,063) treated with RP or RT in Brazil, a significant decline in patients receiving RT or RP (−6.043 cases; p = 0.0001) was detected. Both treatment procedures (RT or PR) were reduced in all five Brazilian regions comparing the Non-COVID and COVID periods. Overall, there was a reduction on RP and RT procedures in 92% (24/25) and 76% (19/25) of the evaluated states, respectively. Comparing the variation of RT and RP per state between COVID and Non-COVID period, there is a significant difference (−18.6% vs. −29%, p = 0.03) with a higher negative impact on the RP group. The RT and RP variation had no significant relationship with the incidence of COVID cases in the states. Limitations include the non-evaluation of treatment combinations, the impact of hypofractionated radiotherapy, and other factors influencing the treatment choice.ConclusionsDuring the COVID-19 pandemic, the curative treatment with RP and RT of Pca was abruptly limited and affected. However, the number of RP was more impacted than RT during the COVID period.     

The Expression of GHS-R in Primary Neurons Is Dependent upon Maturation Stage and Regional Localization

Ghrelin is a hormone with a crucial role in the regulation of appetite, regulation of inflammation, glucose metabolism and cell proliferation. In the brain ghrelin neurons are located in the cortex (sensorimotor area, cingular gyrus), and the fibres of ghrelin neurons in hypothalamus project directly to the dorsal vagal complex (DVC). Ghrelin binds the growth hormone secretagogue receptor (GHS-R) a G-protein-coupled receptor with a widespread tissue distribution, indeed these receptors are localized both in nonnervous, organs/tissues (i.e. adipose tissue, myocardium, adrenals, gonads, lung, liver, arteries, stomach, pancreas, thyroid, and kidney) as well as in central nervous system (CNS) and higher levels of expression in the pituitary gland and the hypothalamus and lower levels of expression in other organs, including brain. A GHS-R specific monoclonal antibody has been developed and characterized and through it we demonstrate that GHS-R is expressed in primary neurons and that its expression is dependent upon their developmental stage and shows differences according to the brain region involved, with a more pronounced expression in hippocampal rather than cortical neurons. A characterization of GHS-R within the central nervous system is of extreme importance in order to gain insights on its role in the modulation of neurodegenerative events such as Alzheimer’s disease.     

Biogeography of Speciation of Two Sister Species of Neotropical Amazona (Aves,Psittaciformes) Based on Mitochondrial Sequence Data

Coalescent theory provides powerful models for population genetic inference and is now increasingly important in estimates of divergence times and speciation research. We use molecular data and methods based on coalescent theory to investigate whether genetic evidence supports the hypothesis of A. pretrei and A. tucumana as separate species and whether genetic data allow us to assess which allopatric model seems to better explain the diversification process in these taxa. We sampled 13 A. tucumana from two provinces in northern Argentina and 28 A. pretrei from nine localities of Rio Grande do Sul, Brazil. A 491 bp segment of the mitochondrial gene cytochrome c oxidase I was evaluated using the haplotype network and phylogenetic methods. The divergence time and other demographic quantities were estimated using the isolation and migration model based on coalescent theory. The network and phylogenetic reconstructions showed similar results, supporting reciprocal monophyly for these two taxa. The divergence time of lineage separation was estimated to be approximately 1.3 million years ago, which corresponds to the lower Pleistocene. Our results enforce the current taxonomic status for these two Amazon species. They also support that A. pretrei and A. tucumana diverged with little or no gene flow approximately 1.3 million years ago, most likely after the establishment of a small population in the Southern Yungas forest by dispersion of a few founders from the A. pretrei ancestral population. This process may have been favored by habitat corridors formed in hot and humid periods of the Quaternary. Considering that these two species are considered threatened, the results were evaluated for their implications for the conservation of these two species.     

Unusual Circulation Patterns of the Rias Baixas Induced by Minho Freshwater Intrusion (NW of the Iberian Peninsula)

The Minho River, situated 30 km south of the Rias Baixas, is the most important freshwater source flowing into the Western Galician coast (NW of the Iberian Peninsula). The buoyancy generated by the Minho estuarine plume can reverse the normal circulation pattern inside the Rias Baixas affecting the exchange between the Rias and the ocean, changing the input of nutrients. Nevertheless, this inversion of the circulation patterns is not a well-monitored phenomenon. The only published results based on in situ data related to the presence of the Minho River plume inside the Rias de Vigo and Pontevedra correspond to an event measured on spring 1998. In this case unexpectedly higher inflow surface current velocities were found at the Ria de Pontevedra, located further away from Minho River. Thus, the main aim of this study is to research the main factors inducing this unusual pattern on the circulation of the Rias de Vigo and Pontevedra. A numerical model implementation of MOHID previously developed, calibrated, and validated for this coastal area was used. Several scenarios were performed in order to explain the individual effect of the Minho River, rivers discharging into each Rias, and estuarine morphology changes. According to the model results, the Minho River discharge is a key factor in the establishment of the negative circulation, while small rivers inside the Rias slightly attenuate this circulation. The negative circulation was stronger in Ria de Pontevedra independently of the distance of this coastal system from the Minho River mouth, showing that morphologic estuarine features are the main factor justifying the different local circulation patterns.     

A New Species of Plectrocnemia from Sicily (Trichoptera,Polycentropodidae)

Plectrocnemia alicatai sp.n. from Sicily (Nebrodi Mountains) is described and figured from the adult male.     

Absence of high levels of DNA polymerase α activity in the nuclear matrix prepared from mouse erythroleukemia cells

We have examined the association of DNA polymerase α activity with the nuclear matrix prepared by different techniques from mouse erythroleukemia cells. At variance with the data obtained using other cell types we have found that only a small amount (less than 2%) of nuclear DNA polymerase α activity resisted extraction with high-ionic strength buffers, even if nuclei were heat-stabilized by incubation at 37°C for 45 min prior to subfractionation. The recovery of DNA polymerase α activity bound to the matrix was unaffected by the type of extracting agent used (NaCl or (NH₄)₂ SO₄), by the extraction sequence or by the method employed for obtaining nuclei. These results could indicate that in some types of cells the nuclear matrix is not involved in DNA replication.